研究者基本情報

• 医学博士, 大阪大学

• https://researchmap.jp/read0106658

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901011983527701
• https://www.czc.hokudai.ac.jp/biores/
• https://www.czc.hokudai.ac.jp/biores/en/

• 200901011983527701

• 結核菌
• PCR
• 遺伝子変異
• リコンビナント蛋白質
• 分子疫学
• 多剤耐性
• 超多剤耐性
• DNAチップ
• DNAジャイレース
• レクチン
• 補体
• 結核
• tuberculosis

• ライフサイエンス, 応用生物化学, CHO細胞、組換えタンパク質生産
• ライフサイエンス, 衛生学、公衆衛生学分野：実験系を含まない
• ライフサイエンス, 衛生学、公衆衛生学分野：実験系を含む
• ライフサイエンス, 医療管理学、医療系社会学
• その他, その他, 病態検査学
• ライフサイエンス, 細菌学

• 博士課程, 国際感染症学院

研究活動情報

• 2025年09月, モンゴル国 食品・農牧・軽工業大臣, 食品・農牧・軽工業大臣勲章
  食品・農牧・軽工業への貢献と取組
  鈴木 定彦
• 2025年02月, タイ・タマサート大学, 公衆衛生学名誉博士号
  タイの公衆衛生学への学術的貢献
• 2022年10月, タイ マヒドン大学, 公衆衛生学 名誉博士号
  タイの公衆衛生微生物学への学術的貢献
  鈴木 定彦
• 2021年03月, 公益財団法人結核予防会, 秩父宮妃記念結核予防国際協力功労賞
• 2010年, 日本ハンセン病学会賞
  日本国

• Comparative in vivo evaluation of colistin resistance determinants in Escherichia coli clone ST131.
  Toyotaka Sato; Soh Yamamoto; Jirachaya Toyting-Hiraishi; Mana Tohyama; Masaru Usui; Hiharu Inoue; Noriko Ogasawara; Yoshinori Ikenaka; Wataru Hayashi; Hidetaka Kosako; Masato Suzuki; Noriyuki Nagano; Takayuki Wada; Chie Nakajima; Yasuhiko Suzuki; Motohiro Horiuchi; Satoshi Takahashi; Shin-Ichi Yokota; Yutaka Tamura
  EBioMedicine, 131, 106423, 106423, 2026年08月05日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Colistin is a last-resort antimicrobial for multidrug-resistant (MDR) Gram-negative infections. Health risks associated with colistin resistance are commonly inferred from resistance phenotypes, despite limited in vivo evidence linking resistance determinants to pathogenic outcomes. Whether distinct colistin resistance determinants confer differential clinical risks remains unknown. METHODS: Using the MDR Escherichia coli ST131 clone, we constructed isogenic mutants harbouring representative plasmid-mediated (mcr-encoding plasmids) or chromosomal (pmrAB) colistin resistance determinants. We systematically evaluated antimicrobial susceptibility, in vivo fitness, virulence, and therapeutic efficacy using murine infection models in female BALB/c mice. Transcriptomic, biochemical, and genetic analyses were performed to identify determinant-specific pathogenic mechanisms. FINDINGS: Clinical risk associated with colistin resistance was highly determinant-specific. Acquisition of pIncI2_mcr-1, pIncP1_mcr-3, or pmrA mutations significantly attenuated in vivo fitness and virulence, whereas pIncFII_mcr-5 and pmrB mutations preserved pathogenicity and caused marked colistin treatment failure. We identified two plasmid-encoded virulence attenuation factors, VafA and VafB, carried on pIncI2_mcr-1. These factors interacted with adenylate cyclase (CyaA), reprogrammed the ST131 transcriptome, suppressed purine biosynthesis, and reduced bacterial growth and virulence independently of colistin resistance itself. INTERPRETATION: Health risks of colistin-resistant E. coli cannot be inferred from resistance phenotypes alone. Determinant-specific in vivo evaluation reveals clinically important heterogeneity in pathogenic potential and treatment outcomes. Surveillance and risk assessment frameworks should prioritise resistance determinants that preserve virulence and compromise last-line therapy, rather than treating colistin resistance as a uniform clinical threat. FUNDING: Food Safety Commission of Japan, the Japan Agency for Medical Research and Development (AMED), JSPS KAKENHI.
• Application of multiplex PCR-based nanopore sequencing for rapid detection and surveillance of antimicrobial-resistant Mycoplasma bovis in Japanese dairy cattle.
  Masaru Usui; Masashi Ebisawa; Shingo Okamura; Azul Noda; Akira Fukuda; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, 14, 8, e0124226, 2026年08月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, UNLABELLED: Mycoplasma bovis causes mastitis and respiratory disease, leading to economic losses in the dairy industry. Conventional culture and antimicrobial susceptibility testing require approximately 2 weeks, promoting empirical antimicrobial use and emergence of resistant strains, highlighting the need for rapid detection methods. Resistance-associated mutations have been detected in rrl and rrs (for macrolides, lincosamides, tetracyclines, and phenicols) and gyrA and parC (for fluoroquinolones), providing targets for a rapid prediction. We developed a multiplex PCR-based nanopore sequencing method capable of simultaneously analyzing up to 24 samples per run to detect mutations in rrl, rrs, gyrA, and parC, and infer the antimicrobial susceptibility of M. bovis within 6 h. Using 329 isolates from cattle collected in Japan (2013-2016 and 2023-2025), we linked genotypes to the minimum inhibitory concentrations of seven antimicrobials and predicted the susceptibility of all isolates. A clear association was observed between specific mutations and susceptibility to multiple antimicrobials, suggesting that susceptibility can be predicted based on target gene sequence. Subsequently, the temporal trends in the prevalence of resistance-associated mutations were examined annually. High-level macrolide- and tetracycline-associated mutations (rrl A2059/A2060, rrs G1058) and dual gyrA-parC mutations increased markedly in recent isolates, with frequencies rising from 1.8% to 43.3%, 0.9% to 41.5%, and 59.8% to 79.8%, respectively, during 2013-2016 and 2023-2025. This nanopore-based platform enables rapid genetics-based antimicrobial guidance and simultaneous analysis of up to 24 samples on a low-cost flow cell, providing a practical tool for clinical decision-making and surveillance of emerging multidrug-resistant M. bovis in dairy cattle. IMPORTANCE: Mycoplasma bovis is a major cause of bovine mastitis and respiratory disease, leading to substantial economic losses and increased antimicrobial use in the dairy industry. Because conventional culture and susceptibility testing are time-consuming, empirical treatment is common, often resulting in therapeutic failure and the emergence of multidrug-resistant strains. This study developed a rapid diagnostic platform using multiplex PCR and nanopore sequencing to predict antimicrobial susceptibility within only 6 h. Our analysis of 329 Japanese isolates reveals a significant temporal increase in mutations associated with resistance to macrolides, tetracyclines, and fluoroquinolones between 2013-2016 and 2023-2025. This cost-effective method enables simultaneous analysis of multiple samples, providing a practical tool for evidence-based clinical decision-making. These findings highlight the urgent need for molecular surveillance to monitor and control the spread of highly resistant M. bovis lineages in global cattle populations.
• EDTA potentiates gentamicin and ofloxacin antibacterial activity against biofilms of methicillin-resistant Staphylococcus pseudintermedius derived from canine superficial pyoderma.
  Masaru Usui; Chie Nakajima; Yasuhiko Suzuki; Koichi Okamura; Tadato Komatsu; Jean-Marc Ghigo; Christophe Beloin
  Veterinary microbiology, 319, 111072, 111072, 2026年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, Canine pyoderma often results from infections caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP), which frequently exhibits multidrug resistance and potent biofilm-forming capabilities. Therefore, veterinary clinicians have limited effective antibiotic options. This study aimed to investigate the potential of ethylenediaminetetraacetic acid (EDTA) combined with antibiotics commonly used to treat canine pyoderma (gentamicin and ofloxacin) on MRSP biofilms in vitro. We performed in vitro biofilm survival assays to determine whether EDTA enhances the efficacy of gentamicin and ofloxacin against MRSP in biofilms. MRSP biofilms were cultured on polyvinyl chloride plates and exposed to high concentrations of gentamicin or ofloxacin. Survival rates varied among strains; however, ofloxacin proved to be more effective than gentamicin in reducing bacterial viability. Notably, some strains exposed to gentamicin showed survival rates exceeding 10%. Co-administration of EDTA with these antibiotics decreased MRSP survival in biofilms compared to antibiotic treatment alone, suggesting that EDTA augments the bactericidal activity of gentamicin and ofloxacin. This effect was particularly striking in antibiotic-tolerant strains, where the addition of EDTA markedly improved survival reduction beyond that achieved with antibiotics alone. These findings underscore the potential of EDTA as an adjunct treatment to enhance the effectiveness of antibiotics against MRSP-induced pyoderma.
• Immune Responses to Live-Attenuated Prime-Boost Vaccination Are Independent of Injection Site in Calves.
  Mari Ikehata; Tomohiro Okagawa; Hayato Nakamura; Maho Inoue; Naoya Maekawa; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi; Satoru Konnai
  Microbiology and immunology, 2026年07月17日, ［国際誌］
  英語, 研究論文（学術雑誌）, Vaccination is highly effective in controlling infectious diseases in calves. A prime-boost injection is often administered intramuscularly in the neck and the hip in calves. However, no guidelines have established whether the same vaccination sites could be used for booster vaccinations. This study investigated the influence of intramuscular administration sites for sequential vaccines on immune responses in calves. All calves received the primary live-attenuated viral vaccine into the left side of the neck. Four weeks later, the booster was administered at the same site as the primary vaccine (local boost group) or in the right hip (distal boost group). The neutralizing antibody titers did not differ significantly between the groups. To assess T-cell responses to viral antigens after booster vaccination, the expression levels of lymphocyte activation markers CD25 and CD69 were measured in peripheral blood mononuclear cells (PBMCs). The site of booster administration had no significant effect on the activation of CD4+ and CD8+ T cells. Furthermore, vaccine-induced production of interferon-γ, tumor necrosis factor-α, and interleukin-6 in PBMC culture supernatants did not differ significantly between the groups. This study detected no significant differences in vaccine-specific immune responses between the local and distal booster vaccination sites in calves.
• Development of a Novel Real-Time PCR Assay Differentiating Burkholderia mallei From Burkholderia pseudomallei.
  Ai Koshikawa; Yoshiki Ichikawa; Mitsuru Nakase; Apichai Tuanyok; Vannarat Saechan; Keisuke Aoshima; Hideaki Higashi; Chie Nakajima; Yasuhiko Suzuki; Vanaabaatar Batbaatar; Takashi Kimura
  Microbiology and immunology, 70, 6, 305, 314, 2026年06月, ［国際誌］
  英語, 研究論文（学術雑誌）, Glanders is a zoonotic disease caused by Burkholderia mallei (Bm). Bm is phylogenetically similar to B. pseudomallei (Bp), the causative agent of melioidosis, making it difficult to differentiate between them. Recently, the PCR method recommended by the World Organisation for Animal Health (WOAH) failed to detect a Kuwait strain of Bm, and the WOAH has cautioned that ongoing Bm evolution may lead to the emergence of variants that escape standard assays. Therefore, this study aimed to develop a novel real-time PCR method to discriminate between Bm and Bp. Local and web-based BLAST searches identified a 494-bp sequence conserved across Bm but absent from other bacterial genomes, including Bp, except for one B. thailandensis strain. The optimized probe-based real-time PCR targeting this sequence detected the genomes of five Bm isolates but did not amplify DNA from closely related Burkholderia species. In clinical specimens from Mongolia, this assay amplified Bm DNA at an equivalent detection rate to the WOAH-recommended real-time PCR method. These findings provide a novel, highly sensitive diagnostic method for differentiating glanders from melioidosis and suggest its potential use as an alternative method in clinical applications. Further verification using a large number of samples collected from various regions will be necessary in the future.
• Recombinant proteins expressed in Mycolicibacterium smegmatis enhance antibody-based detection of bovine tuberculosis.
  Eomseob Jang; Kilhan Kwak; Norikazu Isoda; Kazuhiro Matsuo; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Veterinary research, 57, 1, 2026年05月08日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a zoonosis that threatens public health and causes substantial economic losses in livestock. The suboptimal Escherichia coli-expressed recombinant proteins limit the diagnostic performance of current bTB serological tests. To overcome this limitation, we evaluated Mycolicibacterium smegmatis as an expression host capable of producing recombinant antigens with post-translational modifications comparable to those of M. bovis. Ten antigen candidates were individually expressed in E. coli using the pET-26b( +) vector and in M. smegmatis using the pSOΔBam vector. Their diagnostic performance was evaluated using an enzyme-linked immunosorbent assay (ELISA) with plasma samples from interferon-gamma release assay (IGRA)-negative (n = 30) and -positive (n = 46) cattle in South Korea, followed by receiver operating characteristic (ROC) curve analysis. Among the single antigens, LprA expressed in M. smegmatis demonstrated diagnostic performance comparable to that of the well-established antigen MPB70 (sensitivity: 50.0%, specificity: 96.6%, AUC: 0.791). In addition, several M. smegmatis-derived antigens showed higher concordance with the IGRA results, as assessed by Cohen's kappa and Fisher's exact tests, and a stronger association between age and antigen-specific antibody responses was observed among IGRA-positive cattle. Moreover, a multiple logistic regression model incorporating eight antigens, including those derived from both hosts, achieved high predictive accuracy for IGRA results (sensitivity: 87.0%, specificity: 100%, AUC: 0.991). These findings suggest that M. smegmatis is a promising host for identifying novel antigens and that a multi-host strategy may improve bTB serodiagnosis.
• Re-emergence of equine glanders in Mongolia based on region-wide serosurveillance.
  Batchuluun Enkhtuul; Ochirbat Khurtsbaatar; Baasansuren Lkham; Tumurtogtokh Agiimaa; Jugderkhorloo Unenbat; Burenbaatar Buyanbadrakh; Sugir Ninjbulgan; Borjigin Liushiqi; Yasuhiko Suzuki; Takashi Kimura; Vanaabaatar Batbaatar
  Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc, 38, 3, 505, 508, 2026年05月, ［国際誌］
  英語, 研究論文（学術雑誌）, Glanders, a zoonotic disease caused by Burkholderia mallei, has re-emerged in Mongolia after decades of control. We conducted nationwide serosurveillance from 2021 to 2024 to assess the prevalence and geographic distribution of glanders. Using random 3-stage cluster sampling, we collected 3,001 horse serum samples from 332 herds. Those herds were in 46 soums (administrative districts equivalent to counties) in 13 provinces and in 3 districts in Ulaanbaatar. Sera were tested using the complement fixation test, and positive results were confirmed by immunoblotting and ELISA. Overall seroprevalence was 1.03% (95% CI: [0.7, 1.5]), with positive cases detected in 69.2% of provinces, 34.8% of soums, and 7.2% of herds. The highest prevalence was in the eastern region (2.5%), particularly in Sukhbaatar province (4.5%). None of the seropositive horses had clinical signs of infection. Compared with the 0.19% seroprevalence found in the 2011 nationwide surveillance program, our finding of a 5-fold increase (1.03%) indicates a resurgence of glanders. The likely drivers include reduced veterinary oversight and unrestricted equid movement for racing and breeding. Geographic and environmental factors may also influence transmission. Our results underscore the need for continued surveillance, movement control based on laboratory testing, and increased awareness among herders to prevent the further spread of glanders in Mongolia.
• Genomic comparison of clinical strains of Mycobacterium shinjukuense in Japan reveals low diversity and stable genome structures.
  Takayuki Wada; Hiharu Inoue; Shiomi Yoshida; Yoshiro Murase; Yuriko Igarashi; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Satoshi Mitarai
  Microbial genomics, 12, 5, 2026年05月, ［国際誌］
  英語, 研究論文（学術雑誌）, Mycobacterium shinjukuense, a rare non-tuberculous mycobacterial species closely related to Mycobacterium tuberculosis, remains poorly characterized at the genomic level. To obtain insights into its intraspecies genomic diversity and structure variation, we performed whole-genome sequencing on 18 clinical strains of M. shinjukuense collected from Japan between 2010 and 2017. Phylogenetic analysis revealed limited overall genetic diversity, with several clonal clusters likely representing identical strains. The phylogeny exhibited a largely star-like topology with few single nucleotide variations accumulated over time, suggesting a clonal expansion. Complete genome sequencing of five representative strains revealed high synteny, with no large-scale rearrangements, suggesting stable genomic structures. One strain, MSJ-01, harboured a unique 30 kb insertion region, possibly acquired via horizontal gene transfer. These findings provide insights into the genomic diversity and structure of M. shinjukuense, suggesting both its evolutionary stability and its potential to incorporate foreign DNA. This work expands upon available genomic resources and supports the utility of M. shinjukuense as a model for understanding genome evolution in the M. tuberculosis-associated phylotype lineage.
• Antimicrobial susceptibility of Escherichia coli isolated from wild deer (Cervus nippon yesoensis) and fox (Vulpes vulpes schrencki) in Hokkaido: a pilot study on sustainable antimicrobial resistance monitoring.
  Yui Kawabata; Akira Fukuda; Rin Sato; Hirokazu Kouguchi; Chie Nakajima; Yasuhiko Suzuki; Kohei Makita; Tetsuo Asai; Masaru Usui
  The Journal of veterinary medical science, 88, 4, 642, 648, 2026年04月02日, ［国内誌］
  英語, 研究論文（学術雑誌）, In Japan, sustainable national antimicrobial resistance (AMR) monitoring has been established in both human and veterinary fields. However, AMR monitoring in the environment, including wildlife, remains limited. This study aimed to assess the possibility of sustainable monitoring using wild deer transported to slaughterhouses and wild foxes surveyed for Echinococcus multilocularis. Escherichia coli, a common AMR indicator bacterium, was isolated from rectal swabs of deer and foxes using Chromagar ECC, with and without antimicrobials (cefotaxime (CTX) or nalidixic acid (NA). Antimicrobial susceptibility was determined, and β-lactamase genes were detected using polymerase chain reaction. Plasmids carrying β-lactamase genes were analyzed by whole-genome sequencing. A total of 104 E. coli strains were isolated from (103/120, 85.8%) deer and 61 strains from (56/99, 56.6%) foxes using medium without antimicrobials. Using a medium containing CTX and NA, two and three strains were isolated, respectively, exclusively from foxes. All deer strains were susceptible to the tested antimicrobials. However, 0-11.5% of fox strains from medium without antimicrobials (n=61) demonstrated resistance. Three strains from foxes had β-lactamase genes in plasmid. Finally, this study demonstrates the feasibility of sustainable AMR monitoring using wild deer transported to a slaughterhouse and wild foxes surveyed for E. multilocularis.
• In Vitro Characterization of an Equinized Anti-PD-L1 Antibody for Cancer Immunotherapy in Horses.
  Takeru Horikawa; Naoya Maekawa; Tomohiro Okagawa; Wisa Tiyamanee; Otgontuya Ganbaatar; Hayato Nakamura; Mari Ikehata; Maho Inoue; Takeshi Nakanishi; Taro Tachibana; Yukinari Kato; Keiichi Yamamoto; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi; Satoru Konnai
  Veterinary sciences, 13, 4, 2026年04月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Horses develop spontaneous tumors, typically in old age. Although local tumor control can be achieved using conventional therapies, systemic therapies are required to treat recurrent and/or metastatic tumors. Immune checkpoint inhibitors, such as anti-PD-L1 antibodies, have been approved for the treatment of various tumor types in humans; however, little is known about the immunosuppressive roles of the PD-1/PD-L1 pathway in horses, and the therapeutic potential of these inhibitors remains to be elucidated. Previously, we reported that the rat monoclonal anti-PD-L1 antibody 6C11-3A11 cross-reacts with horse PD-L1 to block the PD-1/PD-L1 interaction. To further develop antibodies for therapeutic purposes, their immunogenicity must be reduced to maximize efficacy and safety. To this end, we designed an equinized (equine-ized) anti-PD-L1 antibody, Eq6C11, using the complementarity-determining regions of 6C11-3A11. Eq6C11 had antigen-binding properties comparable to those of 6C11-3A11 and inhibited equine PD-L1 binding to PD-1 in a recombinant protein-based assay. Treatment with Eq6C11 significantly increased IFN-γ and IL-2 production in equine peripheral blood mononuclear cell cultures, suggesting its stimulatory activity on T-cell activation. Although further studies are needed to clarify its immunogenicity and clinical activity, these results encourage further development of Eq6C11 as a candidate immune checkpoint inhibitor for cancer immunotherapy in horses.
• Seroprevalence of tuberculosis and hematological variations in captive and orphaned wild elephants (Elephas maximus maximus) in Sri Lanka.
  Saman K Piyadasa; Buddhika Bandara; Malaka K Abeywardana; Susan K Mikota; Samitha Lakmal; Nelum Aberathne; Ashoka Dangolla; Harsha Ariyarathna; Sagara N Kumara; Champa N Ratnatunga; Michito Shimozuru; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki; Toshio Tsubota
  Veterinary research communications, 50, 3, 2026年03月30日, ［国際誌］
  英語, 研究論文（学術雑誌）, Tuberculosis (TB) is an emerging infectious disease in captive and wild elephants, with implications for animal health, conservation, public health, and related socio-economic activities. Despite Sri Lanka supporting large wild and culturally important captive elephant populations, national-level data on elephant TB remain limited. This study aimed to estimate TB seroprevalence in elephants and examine associations with hematological and demographic variables. A total of 40 clinically healthy elephants were screened, including privately owned animals (n = 5), elephants managed at the Pinnawala Elephant Orphanage (n = 30), and orphaned wild elephants housed at the Udawalawe Elephant Transit Home (n = 5). Blood samples were analyzed using the DUAL PATH PLATFORM (DPP) VetTB assay to detect antibodies against the Mycobacterium tuberculosis complex. Age and sex data were recorded, and their relationships with serological status and hematological parameters were evaluated. The DPP VetTB assay identified a seropositive rate of 15.8% (6/38), with all seropositive elephants detected among captive elephants. Age group was significantly associated with seropositivity, whereas sex showed no significant association. Mean hematological parameters did not differ significantly between seropositive and seronegative elephants. However, significant age-related effects were observed for white blood cell counts and red cell distribution width, with a similar increasing trend noted for mean corpuscular volume. This study provides the first structured serological assessment of TB exposure in Sri Lankan elephants and underscores the role of the DPP VetTB assay as a screening tool, while emphasizing the need for confirmatory diagnostics and long-term surveillance to strengthen TB monitoring and management.
• Insight into the genetic diversity of Mycobacterium bovis isolated from cattle in Ghana.
  David Atomanyi Barnes; Nathan Grant-Biney; Philip Tetteh; Emelia Konadu Danso; Prince Asare; Jeewan Thapa; Tamsin S Barnes; Adwoa Asante-Poku; Samuel Adjei; Stephen V Gordon; Yasuhiko Suzuki; Chie Nakajima
  Microbiology spectrum, 14, 3, e0213325, 2026年03月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine tuberculosis (bTB), caused primarily by Mycobacterium bovis, poses significant risks to cattle and public health in Ghana. Previous studies reported varying prevalence (3%-21%) and M. bovis strain distributions, necessitating a deeper understanding of the molecular epidemiology of bTB to guide control strategies. This study investigated the genetic diversity and phylogenetic relationships of M. bovis isolates from cattle in Ghanaian abattoirs and compared results with strains from other African countries. Spoligotyping analysis of 28 M. bovis isolates confirmed 6 distinct spoligotypes, with SB0944 being the most prevalent (64.3%). Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) genotyping analysis further resolved the isolates into 22 genotypes, with loci MIRU26, QUB26, and ETR-A showing the highest allelic diversity. Mixed infections were found in 10% of culture-confirmed cases, indicating a high risk of co-infection with multiple strains in the area. Comparative analysis revealed that Ghanaian isolates clustered within the African 1 (Af1) clonal complex, consistent with strains from Nigeria, Burkina Faso, and Cameroon, but distinct from the BCG-like and other strains that were dominant in Algeria and, to some extent, in Mali. Minimal strain homogenization of West-Central Africa with other regions suggests localized evolution, shaped by ecological barriers, regulated transhumance, and possible competitive exclusion among strains. These findings provide evidence for the need for region-specific bTB control measures that reflect Africa's unique livestock dynamics and micro-epidemic patterns. Enhanced surveillance with advanced genotyping methods could improve outbreak tracking and inform targeted interventions to mitigate bTB's impact on livestock in this region.IMPORTANCEBovine tuberculosis (bTB), caused primarily by Mycobacterium bovis, is a neglected disease in many low- and middle-income countries, including Ghana. Our study reveals that while M. bovis strains in Ghana show high local genetic diversity, they belong almost exclusively to a single clonal complex (Af1) shared across West-Central Africa. Despite regional regulations governing transhumance and cattle movement, the observed strain mixing suggests an "island-like" evolutionary structure for M. bovis in this area; that is, diverse within West-Central African countries but genetically isolated. This pattern is shaped by natural barriers, such as deserts and forests, which restrict strain flow while permitting intense intra-regional transmission. Understanding M. bovis evolution in this context is essential for tailoring effective, region-specific interventions. Our findings highlight the need to treat West-Central Africa as a community of interconnected but genetically distinct bTB zones, calling for both local action and coordinated regional strategies to mitigate bTB.
• パンデミック型E.coliクローンにおけるコリスチン耐性の健康影響のin vivo再評価(In vivo reassessment of the health impact of colistin resistance in a pandemic E. coli clone)
  トイティン ジラッチャヤ[平石]; 佐藤 豊孝; 山本 聡; 遠山 茉奈; 臼井 優; 小笠原 徳子; 林 航; 長野 則之; 中島 千絵; 鈴木 定彦; 堀内 基広; 高橋 聡; 横田 伸一; 田村 豊
  日本細菌学雑誌, 81, 1, 39, 39, 日本細菌学会, 2026年03月
  英語
• Antibiogram and molecular insights into quinolone resistance in Salmonella spp. from food-producing animals in the Philippines.
  Lawrence P Belotindos; Angel Mae C Magalong; Marvin Bryan S Salinas; Joel A Miguel Jr; Marvin A Villanueva; Claro N Mingala; Chie Nakajima; Yasuhiko Suzuki
  Journal of infection in developing countries, 20, 2, 195, 207, 2026年02月28日, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: The increasing quinolone resistance in food animals in the Philippines has been documented in previous studies. This study aims to investigate the prevalence and underlying molecular mechanisms responsible for quinolone non-susceptibility in Salmonella isolated from food-producing animals. METHODOLOGY: A total of 227 Salmonella isolates were obtained from food-producing animals and their derived food products in the Philippines. These isolates were subjected to antimicrobial susceptibility testing against 17 different agents. Quinolone non-susceptible isolates were screened for mutations in the quinolone resistance-determining region (QRDR) and plasmid-mediated quinolone resistance (PMQR) genes. QRDR- and PMQR-positive isolates were also screened for virulence genes and genotyped using the multilocus sequence typing (MLST) method. RESULTS: Most isolates showed high resistance to tetracycline, ampicillin, streptomycin, sulfamethoxazole-trimethoprim, and nalidixic acid. About 68.3% of the isolates showed resistance to at least one antimicrobial agent, and 44.9% exhibited multidrug resistance. Out of the 74 quinolone non-susceptible isolates, 74.3% carried amino-acid substitutions in the QRDR of GyrA and ParC, 4.1% harbored PMQR genes, and 14.9% had both. High-level resistance was associated with double amino-acid substitutions in GyrA (Ser83Phe + Asp87Tyr) and ParC (Thr57Ser + Ser80Ile), while PMQR-positive isolates displayed variable low resistance. Moreover, 17 unique sequence types (STs) were identified, predominantly S. London ST155, S. Infantis ST32, and S. Anatum ST64. All Salmonella isolates exhibit QRDR mutations and/or PMQR genes that possess virulence factors invA and agfA. CONCLUSIONS: The findings highlight the widespread fluoroquinolone-resistant Salmonella in food-producing animals and their products, posing a significant threat to the effective treatment of Salmonella-related food-borne diseases.
• Different transcriptional regulatory activities of Mycobacterium bovis and Mycobacterium tuberculosis PhoPR systems.
  Jose Maria Urtasun-Elizari; Ruoyao Ma; Hayleah Pickford; Damien Farrell; Viktor Perets; Jesus Urtasun-Elizari; Gabriel Gonzalez; Chie Nakajima; Yasuhiko Suzuki; Apoorva Bhatt; David E MacHugh; Stephen V Gordon
  Access microbiology, 8, 1, 2026年, ［国際誌］
  英語, 研究論文（学術雑誌）, Tuberculosis (TB) is an infectious disease that affects humans and animals. The pathogens that cause TB belong to the Mycobacterium tuberculosis complex (MTBC), with M. tuberculosis and Mycobacterium bovis as the main representatives of human- and animal-adapted strains, respectively. One key genetic regulator of the MTBC members is the PhoPR system, which controls many processes, including the stress response, lipid metabolism and pathogenesis, among others. Previous studies identified a key G71I substitution in the M. bovis PhoR orthologue relative to M. tuberculosis PhoR and suggested that PhoPR might be non-functional in animal-adapted strains, but recent work has highlighted the functionality of PhoPR in M. bovis despite the G71I substitution. Here, we compare the transcriptional effects of the PhoPR system of M. tuberculosis H37Rv and M. bovis AF2122/97 on an M. bovis AF2122/97 ΔphoPR knockout background. Our results show common patterns of gene expression between the two orthologues, but also clear differences in the expression of rubredoxin genes and lipid biosynthetic loci. This work adds to the evidence that the PhoPR system is indeed functional in M. bovis and suggests that PhoPR controls differential transcriptional programmes that are important in the adaptation to human or animal hosts.
• Antimicrobial resistance, extended-spectrum β-lactamase determinants, and virulence gene profiles of Escherichia coli along the pork production chain in central Thailand.
  Watsawan Prapasawat; Achiraya Siriphap; Sirikarn Wiriyasirivaj; Apiradee Intarapuk; Ruttana Pachanon; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  Veterinary world, 19, 1, 52, 64, 2026年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND AND AIM: Antimicrobial resistance (AMR) in foodborne bacteria presents a significant threat to public health, especially in countries with intensive livestock production systems. Pig farming is a major source of animal protein in Thailand and is recognized as an important reservoir of antimicrobial-resistant bacteria. Escherichia coli is commonly used as an indicator organism for monitoring AMR, including extended-spectrum β-lactamase (ESBL) production and pathogenic potential. This study aimed to assess the frequency of AMR, multidrug-resistant (MDR), ESBL determinants, and virulence genes in E. coli isolates collected from slaughterhouses and fresh markets in central Thailand. MATERIALS AND METHODS: A total of 498 archived E. coli isolates were analyzed, including 236 isolates from slaughterhouses (feces and carcasses) and 262 isolates from fresh markets (pork and cutting boards). Antimicrobial susceptibility testing was performed against 18 antimicrobial agents using the disk diffusion method. MDR was defined as resistance to three or more antimicrobial classes. ESBL production was identified through phenotypic confirmatory tests, and ESBL-producing isolates were screened for bla TEM, bla CTX-M, and bla SHV genes by multiplex polymerase chain reaction. All isolates were further examined for select virulence genes linked to major E. coli pathotypes. RESULTS: Overall, 97.4% of E. coli isolates showed resistance to at least one antimicrobial agent, and 87.3% were classified as MDR. ESBL-producing E. coli made up 23.5% of all isolates, with a significantly higher prevalence in slaughterhouses compared to fresh markets (p < 0.05). Among ESBL producers, 97.4% exhibited MDR phenotypes. Most (89.7%) of the ESBL-producing isolates carried at least one bla gene, with bla TEM being the most common, followed by bla CTX-M. Virulence genes were detected at a low frequency (3.2%), mainly involving eaeA, lt, and stp. CONCLUSION: The high prevalence of AMR, MDR, and ESBL-producing E. coli throughout the pork production chain highlights slaughterhouses and fresh markets as key points for the spread of resistant bacteria. These findings emphasize the need for stronger antimicrobial stewardship, better hygiene practices, and ongoing AMR surveillance within the One Health approach to reduce public health risks linked to pork consumption.
• Exhausted CD4+T cells are associated with CCL4-driven immunosuppressive macrophage accumulation in enzootic bovine leukosis.
  Hayato Nakamura; Tomohiro Okagawa; Malik Hamaïdia; Wisa Tiyamanee; Mari Ikehata; Minagi Hirose; Maho Inoue; Luc Willems; Keisuke Maezono; Passawat Thammahakin; Shintaro Kobayashi; Yukinari Kato; Yasuhiko Suzuki; Naoya Maekawa; Shiro Murata; Kazuhiko Ohashi; Satoru Konnai
  Frontiers in immunology, 17, 1808815, 1808815, 2026年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, In enzootic bovine leukosis (EBL), a B-cell lymphoma caused by bovine leukemia virus (BLV) infection, immune remodeling within tumor-affected lymph nodes is currently poorly understood. Here, we analyzed chemokine production and macrophage phenotypes in tumor-affected lymph nodes in EBL, focusing on CCL4. Intracellular cytokine staining revealed that, compared with healthy lymph nodes, EBL tumor-affected lymph nodes showed increased proportions of CCL4 expressing cells, particularly among CD4+ T cells and B cells. Functional migration assays showed that recombinant CCL4 induced robust monocyte migration, with a comparatively modest T-cell migration. To identify lymph node macrophages, we characterized CD11bhiCD172a+ cells and confirmed their macrophage identity based on high expression levels of CD11c, CD14, CD16, and CD68. Using this definition, we found that the CD11bhiCD172a+ population was markedly increased in tumor-affected lymph nodes. Phenotypic analysis revealed an increased proportion of CD163+ and CD163+PD-L1+ macrophages, consistent with the acquisition of an immunosuppressive phenotype. In parallel, macrophages in tumor-affected lymph nodes showed a shift from MHC class I/IIhi to MHC I/IIlo subsets and reduced co-expression of MHC molecules with CD80 and CD86, indicating impaired antigen-presenting features. Collectively, these findings suggest that elevated CCL4 production in tumor lesions induced by EBL is associated with monocyte recruitment and the accumulation of phenotypically altered macrophages, highlighting a chemokine-driven remodeling of the tumor immune microenvironment.
• Detection of carbapenem resistance among third-generation cephalosporin-resistant Enterobacterales from small-scale poultry farms in peri-urban Lusaka, Zambia.
  Situmbeko J Nasilele; Misheck Shawa; Harvey K Kamboyi; Bruno S J Phiri; Tapiwa Lundu; Mike Nundwe; Angela Lungu; Ladslav Moonga; Shohei Ogata; Masahiro Kajihara; Hirofumi Sawa; Yasuhiko Suzuki; Hideaki Higashi; Ntombi B Mudenda; Mudenda B Hang'ombe; Kaampwe Muzandu
  Access microbiology, 8, 1, Microbiology Society, 2026年01月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background. Carbapenem and third-generation cephalosporin (3GC) resistance among Gram-negative bacteria poses a serious threat to human and animal health. This study aimed to identify and characterize carbapenem- and 3GC-resistant Enterobacterales isolated from poultry in Lusaka Province, Zambia.
  
  Methods. Ninety pooled cloacal samples were collected from market-ready broiler chickens in the Chongwe and Chilanga districts of Lusaka Province. The isolates were screened for 3GC and carbapenem resistance using the disc diffusion and broth microdilution methods. PCR and Sanger sequencing were performed for species identification and detection of β-lactamase-encoding ( bla ) genes, including bla _CTX-M , bla _TEM , bla _OXA-1 and bla _SHV . Hierarchical clustering was used to assess phenotypic and genotypic relationships.
  
  Results. A total of 83 3GC-resistant Gram-negative isolates were recovered, of which 12% were also carbapenem resistant. Escherichia coli was the most prevalent species, followed by Klebsiella pneumoniae and Enterobacter spp., then Pseudomonas aeruginosa, other Pseudomonas spp., Acinetobacter baumannii , Citrobacter freundii and Aeromonas caviae . Multidrug resistance occurred in 84.3% of the isolates, with the highest resistance to ampicillin, tetracycline and co-trimoxazole. Overall, 80.7% of the isolates harboured at least one of the four tested bla genes, with bla _CTX-M and bla _TEM being the most common. Hierarchical clustering revealed that isolates from both districts shared similar phenotypic and genotypic resistance patterns.
  
  Conclusions. The presence of multidrug- and carbapenem-resistant Enterobacterales from poultry highlights the emergence of carbapenem resistance in Zambia’s food production sector. The detection of imipenem-resistant isolates indicates the potential for transmission of resistance genes between animals and humans. These findings underscore the need for prudent antimicrobial use, strengthened stewardship and a One Health surveillance approach to contain the spread of carbapenem resistance genes.
• Simultaneous Detection of Fluoroquinolone- and Macrolide-Resistant Campylobacter jejuni/Campylobacter coli in Retail Chicken Meat Using Multiplex-PCR.
  Akira Fukuda; Ayu Matsui; Yuma Furuya; Yasuhiko Suzuki; Yutaka Tamura; Chie Nakajima; Masaru Usui
  Microbial drug resistance (Larchmont, N.Y.), 32, 1, 1, 8, 2026年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, Campylobacter contamination in chicken meat, particularly with fluoroquinolone- and macrolide-resistant strains, is a significant public health concern. Therefore, developing an easy and rapid detection method for fluoroquinolone- and macrolide-resistant Campylobacter will improve food safety. In this study, we designed and evaluated a multiplex-Polymerase Chain Reaction (PCR) method for the simultaneous detection of fluoroquinolone- and macrolide-resistant Campylobacter jejuni and Campylobacter coli in chicken meat. Our multiplex-PCR-targeted mutations in the gyrA and rrl genes of Campylobacter species confer resistance to fluoroquinolones and macrolides, respectively. Overall, this method could detect Campylobacter contamination and identify C. jejuni and C. coli as well as their susceptibility to fluoroquinolone and macrolide. Spiking of chicken meat samples revealed that multiplex-PCR can detect at least 0.72 Colony-Forming Unit (CFU)/g C. jejuni/coli. Among 277 retail chicken meat samples, C. jejuni/coli were detected in 54 samples using multiplex-PCR, with isolation from 52 samples using microbial culture. The susceptibility of the isolates to fluoroquinolones and macrolides was determined using both the PCR and culture methods, and a comparison of these methods showed that the accuracy, specificity, and sensitivity were all above 95%. The culture method required approximately 8 days for Campylobacter isolation and antimicrobial susceptibility testing. Multiplex-PCR could determine the contamination with C. jejuni/coli and susceptibility to fluoroquinolones and macrolides within 2-3 days from the enrichment culture to final determination. These results indicate that the proposed multiplex-PCR enables rapid and simultaneous detection of fluoroquinolone- and macrolide-resistant C. jejuni/coli in chicken meat and its utility for monitoring their contamination in food.
• Genomic characterization of cefotaxime-resistant Proteobacteria isolated from a bat-harboring cave in Zambia.
  Misheck Shawa; Harvey Kakoma Kamboyi; Herman Chambaro; Kyoko Hayashida; Naganori Nao; Joseph Chizimu; Mike Nundwe; Tuvshinzaya Zorigt; Naoko Kawai; Shohei Ogata; Joseph Ndebe; Mwamba Nsofwa; Msangwa Sinjani; Situmbeko J Nasilele; Mulemba Samutela; Manyando Simbotwe; Katendi Changula; Hirofumi Sawa; Bernard M Hang'ombe; Yasuhiko Suzuki; Masahiro Kajihara; Hideaki Higashi
  New microbes and new infections, 68, 101661, 101661, 2025年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, Bats are widely recognized as reservoirs of emerging and re-emerging pathogens, and their ecological interactions with humans and livestock present important opportunities for the transmission of infectious agents and antimicrobial resistance (AMR). However, little is known about the occurrence of resistant bacteria in bat-associated environments in Zambia or their potential role in the maintenance of AMR outside clinical and agricultural settings. This study investigated the genomic characteristics of cefotaxime-resistant Proteobacteria isolated from bat fecal droppings collected at Leopards Hill Cave, an established hotspot for zoonotic pathogens. Four hundred bat fecal samples were cultured on cefotaxime-supplemented MacConkey agar, and those exhibiting bacterial growth were subjected to antimicrobial susceptibility testing and whole-genome analysis. Of the 400 samples processed, four (1 %) yielded growth, resulting in three bacterial species: Pseudomonas aeruginosa (n = 1), Enterobacter mori (n = 1), and Brucella intermedia (formerly Ochrobactrum intermedium) (n = 2). Genomic screening revealed that P. aeruginosa strain CB_234 harbored bla OXA-50, aph(3')-IIb, and catB7, which confer resistance to β-lactams, aminoglycosides, and chloramphenicol, respectively. It also possessed multiple virulence determinants involved in adherence, motility, and secretion systems that enhance host colonization and environmental persistence. Core genome phylogenetic analysis placed CB_234 within a clade exclusively composed of clinical isolates from Nigeria, Thailand, Russia, Kenya, and Ghana, indicating a shared evolutionary lineage among globally dispersed hospital-associated strains. Conversely, environmental isolates from plant and aquatic sources, along with a dog-associated isolate, were phylogenetically distant, highlighting the distinct evolutionary origins. The E. mori isolate carried bla ACT and qnrE resistance genes and plasmid replicons, suggesting potential mobility of resistance traits through horizontal gene transfer. In contrast, the two B. intermedia isolates did not harbor any known AMR genes or plasmid replicons. However, this species is increasingly recognized as an opportunistic pathogen. The detection of AMR-associated bacterial species in a natural bat habitat supports the evidence of resistance determinants circulating in wildlife environments in Zambia. Given that bats are unlikely to encounter clinical antibiotics directly, the persistence of such genes in their environment suggests that natural ecosystems may play an underappreciated role in maintaining AMR reservoirs independent of direct antimicrobial pressure. These findings underscore the importance of incorporating wildlife and environmental niches into national and global AMR surveillance frameworks under a One Health approach to better understand the ecological dimensions of AMR emergence and dissemination.
• Clinical efficacy of anti-programmed death ligand 1 antibody HFC-L1/c4G12 in dogs with malignant tumors: an exploratory study.
  Satoshi Takagi; Michihito Tagawa; Naoya Maekawa; Satoru Konnai; Yumiko Kagawa; Kenji Hosoya; Akinori Yamauchi; Ayano Kudo; Shintaro Kamo; Sangho Kim; Ryohei Kinoshita; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Hayato Nakamura; Yukinari Kato; Shigeki Kanazawa; Tomoyuki Abe; Takuya Furuta; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
  The Journal of veterinary medical science, 87, 12, 1419, 1425, 2025年12月01日, ［国内誌］
  英語, 研究論文（学術雑誌）, Cancer in dogs remains a major challenge in modern veterinary medicine. Immunotherapy using immune checkpoint inhibitors (ICIs) is available for various human tumor types, and recent veterinary clinical studies have shown that ICIs are a promising approach for treating canine cancers. A canine chimeric anti-PD-L1 antibody, c4G12 (HFC-L1), has been investigated for canine cancer immunotherapy; however, its clinical benefits have not been well characterized in tumors other than pulmonary metastatic (stage IV) oral malignant melanoma (OMM). To explore the efficacy and safety of HFC-L1, we conducted a clinical study in dogs with stage I-III OMM or other tumor types (n=12). HFC-L1 treatment at a dose of 5 mg/kg every 2 weeks was well tolerated, and no grade 3 or higher treatment-related adverse events were reported. Among the dogs eligible for response evaluation (n=10), a partial response was observed in one dog with squamous cell carcinoma, resulting in an objective response rate of 10%. In addition, in a dog with ceruminous cell carcinoma, clinical evidence of a tumor response was observed in metastatic lung lesions. Together, these results suggest that the HFC-L1 therapy is applicable for the treatment of various tumor types, although its clinical benefits should be further evaluated in clinical studies involving a larger number of dogs with each tumor type.
• Bacterial contamination level and characterization of antimicrobial-resistant bacteria in commercial pet foods in Japan.
  Akira Fukuda; Kazu Yamaura; Kazuyoshi Tokumoto; Yasuhiko Suzuki; Chie Nakajima; Shoichiro Yukawa; Masaru Usui
  One health (Amsterdam, Netherlands), 21, 101197, 101197, Elsevier BV, 2025年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, With the growing pet market, various types of pet food become available. Pet foods, especially raw meat-based diets (RMBDs), are contaminated with pathogens and antimicrobial-resistant bacteria, leading to health concerns for pets and humans. The bacterial contamination levels in pet food, including the presence of antimicrobial-resistant bacteria, have not been extensively studied in Japan. To address this issue in commercial pet foods in Japan, we evaluated the standard plate counts (SPCs) of various pet food samples, and isolated and characterized Escherichia coli and Enterococcus spp. A total of 129 pet foods (48 RMBDs, 21 heat-treated foods, and 60 treats) were purchased, and SPC quantification and isolation of E. coli and Enterococcus spp. were performed. SPCs in RMBD were significantly higher than in heat-treated foods and treats. Specifically, 50.0 % of the RMBD samples had SPCs exceeding 106 CFU/g. E. coli was isolated only from 62.5 % of RMBDs. Four cephalosporin-resistant E. coli strains harboring bla genes were detected, among which, one carried mcr conferring resistance to colistin. Enterococcus spp. were isolated from 89.6 % of RMBDs and 23.3 % of treats. Linezolid-non-susceptible E. faecalis harboring optrA or poxtA genes were detected in four RMBDs. Pet food may be contaminated with bacteria; some RMBDs are contaminated at concentrations >106 CFU/g, and with veterinary and human clinically important antimicrobial-resistant bacteria. To prevent health risks in both humans and pets associated with pet food, ensuring the hygienic management of pet food, especially RMBDs, and promoting accurate knowledge among pet owners are important.
• Diagnostic Stewardship Trends and Antimicrobial Resistance Profiles of Bacteria Isolated in Zambia: A Five-Year Retrospective Study (2020-2024).
  Joseph Yamweka Chizimu; Aubrey Chichonyi Kalungia; Steward Mudenda; Zoran Muhimba; Chileshe Lukwesa; Webrod Mufwambi; Amon Siame; Kelvin Mwangilwa; Priscilla Gardner; Jimmy Hangoma; Victor Daka; Chikwanda Chileshe; Ntombi B Mudenda; Maisa Kasanga; Misheck Shawa; Herman Chambaro; Duncan Chanda; Taona Sinyawa; Bertha Chibwe; Kaunda Kaunda; Kaunda Yamba; O-Tipo Shikanga; Freddie Masaninga; Mpela Chibi; Sandra Diana Mwadetsa; Doreen Mainza Shempela; Mwendalubi Albert Hadunka; Samson Mukale; Andrew Bambala; Malambo Mutila; Loveness Sakalimbwe; Fred Mulako Simwinji; Geoffrey Mainda; Chie Nakajima; Ruth Nakazwe; Fusya Goma; Nyambe Sinyange; Yasuhiko Suzuki; John Bwalya Muma; Roma Chilengi
  Antibiotics (Basel, Switzerland), 14, 11, 2025年11月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND/OBJECTIVES: The right diagnostic tests, for the right patient, at the right time, are key to optimising antimicrobial use (AMU) and preventing antimicrobial resistance (AMR). This study evaluated diagnostic stewardship trends and AMR patterns in Zambian surveillance sentinel sites from 2020 to 2024. METHODS: This descriptive, retrospective study analysed routine laboratory data from January 2020 to December 2024 at seven designated AMR surveillance sentinel sites across Zambia. Data on clinical specimens submitted for antimicrobial susceptibility testing were extracted from WHONET and analysed by year, specimen type, and antimicrobial susceptibility profile. RESULTS: A total of 184,788 bacteriology specimens were processed over five years. Urine was the most frequently collected specimen, peaking above 20,000 in 2024. Escherichia coli was the most commonly isolated organism among 15 priority pathogens, comprising 25.9% of the 30,013 isolates. Though a statistically significant increasing trend in total organism isolations was observed annually, only Shigella sp. demonstrated a substantial increase in non-susceptibility to azithromycin (p = 0.027). High resistance was observed with doxycycline, azithromycin, clindamycin, trimethoprim/sulfamethoxazole, ciprofloxacin, and rifampicin, exhibiting resistance ranging from 50% to 80%. Critical AMR alerts included 65% for Vancomycin-Resistant Enterococcus (VRE), 72% for linezolid, and 44% for carbapenems, and possible ESBL-producing Enterobacterales showing the highest overall resistance at 35%, across sentinel sites. CONCLUSIONS: Zambia faces a concerning and significant increase in AMR, with high resistance prevalence across commonly used antibiotics. Critical resistance alerts for VRE, linezolid, carbapenems, and possible ESBL-producing Enterobacterales underscore an urgent need for robust antimicrobial stewardship and continuous diagnostic surveillance.
• Antimicrobial Consumption and Utilisation in Zambia: Results from the Analysis of National Data for the Human and Animal Health Sectors.
  Steward Mudenda; Joseph Yamweka Chizimu; Victor Daka; Maisa Kasanga; Webrod Mufwambi; Kelvin Mwangilwa; Jimmy Hangoma; Priscilla Gardner; Chikwanda Chileshe; Ntombi B Mudenda; Taona Sinyawa; Amon Siame; Mwendalubi Hadunka; Fred Mulako Simwinji; Kaunda Kaunda; Mpela Chibi; Zoran Muhimba; Elimas Jere; Makomani Siyanga; Peter Lisulo; Freddie Masaninga; Samson Mukale; Andrew Bambala; Misheck Shawa; Charles Chileshe; Bertha Chibwe; Mercy Mukuma; Bruno S J Phiri; Geoffrey Mainda; Yasuhiko Suzuki; Fusya Goma; John Bwalya Muma; Roma Chilengi
  Antibiotics (Basel, Switzerland), 14, 11, 2025年11月07日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background/Objectives: Antimicrobial Resistance (AMR) remains a growing public health threat, underscoring the need for robust surveillance of Antimicrobial Consumption (AMC) and Antimicrobial Use (AMU). This study analysed AMC and AMU trends in Zambia's human and animal health sectors, identifying priority areas for antimicrobial stewardship (AMS) under a One Health framework. Methods: A retrospective study was conducted in February 2025, utilising data from 2018 to 2023. Sources of data included the Zambia Medicines Regulatory Authority (ZAMRA) and the WOAH Animal Antimicrobial Use (ANIMUSE) Global Database platform. AMC was analysed using the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) methodology. Antimicrobials were classified using the WHO Anatomical Therapeutic Chemical (ATC) system, and consumption was measured in Defined Daily Doses (DDDs) per 1000 inhabitants per day (DID). Antibiotics were further categorised using the WHO Access, Watch, and Reserve (AwaRe) classification. Data analysis was performed using IBM SPPS version 25.0. Results: In the human health sector, oral antibiotics accounted for 88% of total consumption. Penicillins (33%), cephalosporins (19.2%), and macrolides (12.4%) were the most consumed classes. In 2023, 98,651,882.42 DDDs per 1000 inhabitants/day were recorded, with amoxicillin, ceftriaxone, and sulfamethoxazole/trimethoprim leading as the most consumed antibiotics. According to the consumption of antibiotics by the WHO AwaRe classification, 47% were Access, 40% Watch, and 3% Reserve group antibiotics. In animal health, tetracyclines dominated (63%), followed by sulphonamides (26%) and penicillins (11%). AMU in animal health peaked in 2023. Conclusions: This study found high AMC and AMU, especially Watch-group antibiotics and tetracyclines, highlighting the need for strengthened antimicrobial stewardship, regulatory oversight, and integrated One Health surveillance to mitigate AMR risks in Zambia.
• Impact of Multidisciplinary-Led Implementation of Antimicrobial Stewardship Programs in Zambia: Findings and Implications.
  Joseph Yamweka Chizimu; Steward Mudenda; Victor Daka; Webrod Mufwambi; Zoran Muhimba; Kaunda Yamba; Misheck Shawa; Kelvin Mwangilwa; Jimmy Hangoma; Sombo Fwoloshi; Amon Siame; Kaunda Kaunda; Andrew Bambala; Kenneth Kapolowe; Priscilla Nkonde Gardner; Duncan Chanda; Shempela Doreen; Charles Chileshe; Paul Simujayang Ombe; Ntombi B Mudenda; Loveness Sakalimbwe; Aubrey C Kalungia; Chikwanda Chileshe; Taona Sinyawa; Maisa Kasanga; Raphael Chanda; Samson Mukale; Shikanga O-Tipo; Evelyn Wesangula; Cephas Sialubanje; Adrian Muwonge; Fred Simwinji; Chie Nakajima; Freddie Masaninga; Fusya Goma; Nyambe Sinyange; Yasuhiko Suzuki; John Bwalya Muma; Roma Chilengi
  Antibiotics (Basel, Switzerland), 14, 11, 2025年11月07日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background/Objectives: Antimicrobial resistance (AMR) is a critical global health threat, with sub-Saharan Africa disproportionately affected. Antimicrobial stewardship (AMS) programs are essential in combating AMR; however, data on their implementation in resource-limited settings like Zambia remain scarce. This study assessed the post-implementation status of World Health Organization (WHO) AMS core elements in selected public hospitals in Zambia. Methods: A cross-sectional pre- and post-intervention survey was conducted in 11 public hospitals across Zambia's 10 provinces. Baseline (pre-implementation) and 12-month follow-up (post-implementation) assessments were carried out using the WHO-adapted Periodic National and Healthcare Facility Assessment Tool. The six AMS core elements evaluated included leadership, accountability, AMS actions, education, monitoring, and feedback. Results: The average AMS program score increased from 59% at pre-implementation to 81% at post-implementation. Significant improvements were observed in education and training (+36%) and accountability (+31%). While leadership and monitoring also showed positive trends, gaps persisted in AMS actions (63%) and feedback/reporting mechanisms (68%). Drug and Therapeutics Committee (DTC) functionality improved by 23%, with 90% of facilities now holding regular DTC meetings. Implementation of AMS actions, such as ward rounds, rose from 0% to 73%. Challenges remained in clinical audit feedback, resource mobilization, and prescribing optimization. Variability across facilities highlighted differences in leadership, resources, and technical capacity. Conclusions: AMS implementation in Zambia improved substantially across key domains. However, sustained leadership, adequate financing, and continuous capacity-building are needed to address persistent gaps and ensure long-term success in mitigating AMR.
• Emergence of livestock-associated MRSA clonal complex 398 in Thailand's swine industry.
  Pawarut Narongpun; Pattrarat Chanchaithong; Wimonrat Tanomsridachchai; Narong Nuanmuang; Jeewan Thapa; Junya Yamagishi; Orasa Suthienkul; Pimlapas Leekitcharoenphon; Frank M Aarestrup; Chie Nakajima; Yasuhiko Suzuki
  The Journal of antimicrobial chemotherapy, 80, 11, 2912, 2917, 2025年11月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Livestock-associated MRSA (LA-MRSA) clonal complex (CC) 398 is primarily found among pigs across Europe. However, CC398 has also been sporadically identified in several Asian countries, including Thailand. This study aimed to examine the drivers contributing to the emergence of LA-MRSA CC398 in Thailand's swine industry. METHODS: Whole-genome sequencing data of 18 LA-MRSA CC398 isolates from pigs, retail pork and swine workers in Thailand were analysed. Additionally, a total of 1197 qualified genomes from various sources in 24 countries were retrieved from Pathogenwatch. Subsequently, two SNP-based phylogenetic trees were reconstructed using maximum likelihood (n = 1215) and Bayesian inference (n = 168). RESULTS: Our findings revealed that Staphylococcus aureus isolates with the CC398-SCCmec Vc (5C2&5)-t034 genotype were closely related to European isolates, including those from Denmark. In contrast, S. aureus isolates belonging to the CC398-composite SCCmec-t034 formed a phylogenetically distinct cluster. CONCLUSIONS: This study reports that the CC398-SCCmec Vc (5C2&5)-t034 genotype identified in Thai pigs may have originated from Danish swine populations, possibly introduced into Thailand through international livestock movement. The CC398-composite SCCmec-t034 genotype was also detected in domestic pigs; however, it appears to have evolved independently from the CC398-SCCmec Vc (5C2&5)-t034 genotype. Bayesian phylogenetic analysis estimates that the common ancestor of the composite genotype emerged earlier than that of the CC398-SCCmec Vc (5C2&5)-t034 genotype, indicating a separate evolutionary origin.
• Antimicrobial Stewardship Program Implementation, Perceptions, and Barriers in Zambia: A Cross-Sectional Study Among Healthcare Professionals.
  Steward Mudenda; Joseph Yamweka Chizimu; Victor Daka; Jimmy Hangoma; Kelvin Mwangilwa; Priscilla Gardner; Chikwanda Chileshe; Taona Sinyawa; Zoran Muhimba; Charles Chileshe; Sandra Diana Mwadetsa; Shikanga O-Tipo; Duncan Chanda; Maisa Kasanga; Geoffrey Mainda; Webrod Mufwambi; Samson Mukale; Andrew Bambala; Fusya Goma; Aubrey Chichonyi Kalungia; Yasuhiko Suzuki; Brian Godman; John Bwalya Muma; Roma Chilengi
  Antibiotics (Basel, Switzerland), 14, 11, 2025年11月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background/Objectives: Antimicrobial stewardship programs (ASPs) play a vital role in combating antimicrobial resistance (AMR). However, their implementation in Zambia remains variable despite some notable progress. This study assessed healthcare professionals' awareness of the Multisectoral National Action Plan (NAP) on AMR, alongside their perceptions, barriers, and implementation practices related to ASPs. Methods: A cross-sectional survey conducted between August and December 2024 included 364 healthcare professionals (HCPs) in 58 randomly selected public healthcare facilities in Zambia. Data were analysed using IBM SPSS 25.0. Results: Findings revealed that while 75.3% of respondents were aware of the Zambian NAP on AMS, only 68.1% of the respondents reported that their hospitals had established AMS committees. Conversely only 41.2% of the respondents stated that their hospitals possessed hospital-specific treatment guidelines. Encouragingly, 97.5% believed ASPs could enhance clinical outcomes and reduce AMR. Key barriers included limited funding (75.9%), inadequate IT infrastructure (64.1%), limited access to essential data (64%), and healthcare workforce shortages (53.8%). Conclusions: Whilst HCPs in Zambia demonstrated high awareness of the NAP and supported ASP implementation, systemic challenges hindered their consistent execution across health facilities. Gaps in treatment guideline development, AMR data usage, and the integration of antimicrobial susceptibility recording systems into clinical activities must be addressed to strengthen ASP efforts nationwide.
• Enhancement of Vaccine-Induced T-Cell Responses by Probiotics in Calves.
  Mari Ikehata; Tomohiro Okagawa; Hayato Nakamura; Naoya Maekawa; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi; Satoru Konnai
  Vaccines, 13, 11, 2025年10月31日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND/OBJECTIVES: Calves have immature immune systems, hence immunization with vaccines is essential to protect them from infectious diseases. However, immune responses to vaccines vary widely among individuals. Therefore, strategies for enhancing vaccine efficacy are needed, particularly those targeting low responders to vaccines. Probiotics have attracted attention because of their beneficial immunomodulatory effects on the host. Although probiotics may improve calf immunity, their potential to enhance immune responses to vaccines in calves remains unclear. Thus, we investigated whether immune responses to vaccines, especially T-cell responses, are enhanced when calves receive a combination of probiotic supplementation and vaccination. METHODS: Calves were divided into three feeding groups, as follows: negative control feed, live bacteria-mixed feed (Zeosapo KB), and Clostridium butyricum-only feed (CB). After weaning, all calves received two doses of a live attenuated hexavalent viral vaccine. T-cell responses to a vaccine antigen were evaluated by measuring the expression levels of lymphocyte activation markers CD25 and CD69, as well as Th1 cytokine production, in peripheral blood mononuclear cell culture assays. RESULTS: CD25 expression significantly increased in CD4+ T cells four weeks after the booster vaccination in the Zeosapo KB- and CB-fed groups. In addition, the CD25+CD69+ cell ratio in CD4+ T cells was increased in these groups. The production of Th1 cytokines in the culture supernatant was also increased in the CB-fed group. CONCLUSIONS: This clinical study demonstrates that probiotics activate CD4+ T cells and enhance Th1 cytokine responses in vaccinated calves.
• Complete genome sequence of Treponema medium isolated from foot of bovine digital dermatitis in Japan.
  Akira Fukuda; Takashi Murakami; Noritsugu Abe; Yasuhiko Suzuki; Chie Nakajima; Masaru Usui
  Microbiology resource announcements, 14, 10, e0065625, 2025年10月09日, ［国際誌］
  英語, 研究論文（学術雑誌）, Treponema species are the primary causative bacteria of bovine digital dermatitis. This report describes the isolation and complete genome sequencing of Treponema medium strain T1 isolated from a hoof sole swab of a bovine in Japan. Genome sequences were obtained using a combination of long- and short-read sequencing technologies.
• Comprehensive analysis of immune checkpoint molecules profiles phenotype and function of exhausted T cells in enzootic bovine leukosis.
  Hayato Nakamura; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Wisa Tiyamanee; Mari Ikehata; Koume Matsubara; Kei Watari; Kana Kamitani; Maya Saito; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Journal of immunology (Baltimore, Md. : 1950), 214, 10, 2600, 2616, Oxford University Press (OUP), 2025年10月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Abstract
  
  Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), a B-cell lymphoma in cattle. Previous studies have demonstrated that T cells of BLV-infected cattle show increased expression of immune checkpoint molecules, including programmed death-1 (PD-1), lymphocyte-activation gene-3 (LAG-3), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin domain and mucin domain-3 (TIM-3), leading to T-cell exhaustion. However, the key immune checkpoint molecules driving T-cell exhaustion in BLV-induced tumorigenesis remained unclear. In this study, we identified the key immune checkpoint molecules by performing comprehensive flow cytometric analyses of T cells from EBL cattle, and elucidated the phenotype and function of exhausted T cells using a transcriptomic analysis by RNA sequencing and cell culture assays. The comprehensive expression analysis revealed that the proportion of CD4+ and CD8+ T cells co-expressing PD-1 and TIM-3 was significantly increased in the peripheral blood and tumor tissues of EBL cattle compared to healthy cattle. Transcriptomic analysis of PD-1+TIM-3+ T cells revealed the upregulation of genes related to terminal exhaustion and the downregulation of genes related to T-cell differentiation and response in this subset. Additionally, PD-1+TIM-3+ T cells exhibited higher expression of CTLA-4, LAG-3, and Eomes, and lower expression of T-bet, suggesting a terminally exhausted phenotype. Cell culture assays revealed a significant impairment in IFN-γ production in PD-1+TIM-3+ T cells upon stimulation, reflecting severe dysfunction. These findings indicate that PD-1+TIM-3+ T cells play a central role in T-cell exhaustion during BLV-induced tumorigenesis. This study provides valuable insights for future therapeutic strategies against BLV infection.
• Exploratory, Randomized, Dose-Response Study of the Anti-PD-L1 Antibody HFC-L1/c4G12 in Dogs with Pulmonary Metastatic Oral Malignant Melanoma.
  Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Naoya Maekawa; Satoru Konnai; Satoshi Takagi; Michihito Tagawa; Yumiko Kagawa; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Hayato Nakamura; Akinori Yamauchi; Ayano Kudo; Shintaro Kamo; Yukinari Kato; Shigeki Kanazawa; Tomoyuki Abe; Takuya Furuta; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
  Veterinary sciences, 12, 9, 2025年09月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, Oral malignant melanoma (OMM) is a highly aggressive malignancy in dogs. The development of effective systemic therapies is urgently required to improve the treatment of canine OMM. Immunotherapy using immune checkpoint inhibitors (ICIs) has been investigated in canines following their dramatic success in human cancer treatment; however, there is still a need for extensive veterinary clinical studies to clarify and optimize their clinical benefits. Among the ICIs under development for canine cancer immunotherapy, c4G12 (HFC-L1), a canine chimeric anti-PD-L1 antibody, has shown promising efficacy in dogs with pulmonary metastatic OMM in previous clinical studies. However, the optimal dose of HFC-L1/c4G12 has not yet been determined. To explore the dose-response relationship of HFC-L1, a multicenter, randomized clinical study was conducted using three different doses (2, 5, or 10 mg/kg via intravenous infusion every 2 weeks) to treat dogs with pulmonary metastatic OMM (n = 8-9 per group). The safety profiles were similar among the dose groups, and numerically longer median overall survival was achieved in the higher dose groups (5 and 10 mg/kg) than in the 2 mg/kg group. Although the study was exploratory in nature with a small sample size, 5-10 mg/kg should be considered the preferred dose in future clinical studies using HFC-L1.
• イヌ常在菌Staphylococcus pseudintermedius由来SpsQとイヌIgGとの結合性の評価
  竹内寛人; 竹内寛人; 中島千絵; 今内覚; 今内覚; 今内覚; 前川直也; 岡川朋弘; 岡川朋弘; 臼井優; 田村豊; 鈴木定彦; 村田史郎; 大橋和彦; 鈴木定彦; 村田史郎; 大橋和彦
  日本獣医学会学術集会講演要旨集, 168th, 208, 208, (公社)日本獣医学会, 2025年09月
  日本語
• 抗PD-L1ウマキメラ抗体の樹立およびウマの悪性腫瘍に対する抗腫瘍効果の検証
  堀川壮琉; 岡川朋弘; 岡川朋弘; GANBAATAR Otgontuya; TIYAMANEE Wisa; 前川直也; 北内諒; 山家祟史; 鈴木定彦; 鈴木定彦; 賀川由美子; 村田史郎; 大橋和彦; 加藤幸成; 加藤史樹; 今内覚; 今内覚
  日本獣医学会学術集会講演要旨集, 168th, 215, 215, (公社)日本獣医学会, 2025年09月
  日本語
• Genomic insights into ceftazidime resistance in Burkholderia pseudomallei: discovery of A172T mutation and palindromic GC-rich repeat sequences facilitating penA duplication and amplification.
  Apichai Tuanyok; Chie Nakajima; Tiernan Noll; Md Siddiqur Rahman Khan; Pacharapong Khrongsee; Charles A Yowell; Yu-Ping Xiao; Vanaporn Wuthiekanun; Narisara Chantratita; Henry Heine; Kuttichantran Subramaniam; Yasuhiko Suzuki; Direk Limmathurotsakul; Ayalew Mergia
  Antimicrobial agents and chemotherapy, 69, 8, e0022025, American Society for Microbiology, 2025年08月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, ABSTRACT
  
  Ceftazidime (CAZ) resistance in Burkholderia pseudomallei , the causative agent of melioidosis, complicates treatment in endemic regions. This study identified a novel A172T mutation and other known penA mutations as critical contributors to CAZ resistance in a large Thai strain collection. Frequent gene duplication and amplification of penA , likely driven by Palindromic GC-Rich Repeat Sequences, highlights the urgent need for rapid diagnostics and optimized treatment strategies to manage this life-threatening disease effectively.
• Occurrence of cefotaxime-resistant and beta-lactamase-producing Enterobacterales in poultry from small-scale farms in the Copperbelt province of Zambia.
  Situmbeko J Nasilele; Misheck Shawa; Harvey K Kamboyi; Bruno S J Phiri; Herman Chambaro; Tapiwa Lundu; Mike Nundwe; Angela Lungu; Ladslav Moonga; Masahiro Kajihara; Hirofumi Sawa; Yasuhiko Suzuki; Hideaki Higashi; Amon Siame; Ntombi B Mudenda; Mudenda B Hang'ombe; Kaampwe Muzandu
  JAC-antimicrobial resistance, 7, 4, dlaf125, Oxford University Press (OUP), 2025年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, Abstract
  
  Background
  
  The inappropriate use of antimicrobials in poultry farming is associated with the emergence of antimicrobial-resistant Enterobacterales. This cross-sectional study aimed to identify various cefotaxime-resistant and β-lactamase-producing Enterobacterales and characterize their antimicrobial resistance profiles.
  
  Methods
  
  Pooled cloacal and meat samples collected from market-ready broiler chickens in Kitwe and Ndola districts of Zambia were screened for cefotaxime-resistant Enterobacterales. The samples were inoculated on MacConkey agar supplemented with 1 mg/L cefotaxime. The cefotaxime-resistant isolates were further subjected to antimicrobial susceptibility tests. Further, the isolated cefotaxime-resistant Enterobacterales were analysed for blaCTX-M, blaTEM, blaOXA-1-like and blaSHV genes using PCR and Sanger sequencing.
  
  Results
  
  From a total of 114 pooled samples, 81 (71.1%) cefotaxime-resistant Gram-negative strains were isolated. These were dominated by Escherichia coli (77.8%) followed by Klebsiella pneumoniae (6.2%), Pseudomonas spp. (6.2%), Acinetobacter baumannii (4.9%), Pseudomonas aeruginosa (2.5%), Enterobacter spp. (1.2%) and Comamonas aquatica (1.2%). Furthermore, 64.2% of the 81 isolates exhibited multidrug resistance with high resistance (&gt;64%) to ampicillin, co-trimoxazole and tetracycline. The results also showed that 66.7% of the isolates harboured at least one of the four tested bla genes (blaCTX-M, blaTEM, blaOXA-1-like and blaSHV), with the commonest being blaCTX-M (58%) and blaTEM (45.7%).
  
  Conclusions
  
  The study revealed a high prevalence of cefotaxime-resistant Enterobacterales and multidrug resistance involving medically important antibiotics. Four bla genes (blaCTX-M, blaTEM, blaOXA-1-like and blaSHV) were identified. Our results highlight the need to strengthen antimicrobial stewardship programmes and optimize antimicrobial use in poultry farming.
• Unveiling the Genetic Diversity and Antimicrobial Resistance Profiles of Salmonella Population From 2016 to 2020 in Thai Canal Water.
  Jirachaya Toyting-Hiraishi; Toyotaka Sato; Neunghatai Supha; Yuwanda Thongpanich; Motohiro Horiuchi; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki; Fuangfa Utrarachkij
  Environmental microbiology reports, 17, 4, e70160, Wiley, 2025年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, ABSTRACT
  
  Salmonella is one of the important pathogens causing acute gastroenteritis, and antimicrobial‐resistant Salmonella raises a critical public health concern. Canals in Bangkok, Thailand, play a vital role as sources of agricultural and daily water usage. By employing whole genome sequencing to analyse 351 Salmonella genomes isolated between 2016 and 2020, we expanded the understanding of the characteristics and antimicrobial resistance properties of Salmonella enterica found in Bangkok canals, an underrepresented biome in research. Salmonella Agona was the dominant serotype, while S. Typhimurium and its monophasic variant were periodically found. Seven new sequence types (STs) were identified, including STs 11,346, 11,347, 11,348, 11,349, 11,350, 11,351, and 11,352. Seven chromosomal‐mediated gene mutations and 50 antimicrobial resistance genes were detected. The three most common resistance genes were tet(A), bla_TEM‐1B, and qnrS1. The tet(X4) was first identified in the Salmonella population in Thailand, and mcr‐3.1 was also detected. In total, 39.0% of the strains were potentially multidrug‐resistant. The strains carried double amino acid substitutions in GyrA and ParC, and a strain with GyrA substitutions and qnrS1 exhibited the strongest resistance to nalidixic acid and ciprofloxacin. Most of the ceftazidime, ceftriaxone, and cefotaxime‐resistant strains (66.7%) harboured bla_CTX‐M‐55. Col(pHAD28) was the predominant plasmid replicon type. Phylogenetic analysis of Salmonella STs 34 and 213 from canal water and the strains from databases showed the possibility of circulation of STs 34 and 213 between canal water and humans in Thailand and worldwide. These findings shed light on the circulation of antimicrobial‐resistant pathogens in the environmental water and advocate for incorporating environmental sampling into comprehensive AMR surveillance programmes within a One Health framework.
• Investigation of WQ-3810, a Fluoroquinolone with a High Potential Against Fluoroquinolone-Resistant Mycobacterium avium.
  Sasini Jayaweera; Pondpan Suwanthada; David Atomanyi Barnes; Charlotte Poussier; Tomoyasu Nishimura; Naoki Hasegawa; Yukiko Nishiuchi; Jeewan Thapa; Stephen V Gordon; Hyun Kim; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 14, 7, 704, 704, MDPI AG, 2025年07月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background/Objectives: Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC50s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810’s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections.
• Development of a multiplex loop-mediated isothermal amplification (LAMP) method for differential detection of Mycobacterium bovis and Mycobacterium tuberculosis by dipstick DNA chromatography.
  Mwangala L Akapelwa; Thoko F Kapalamula; Lavel C Moonga; Precious Bwalya; Eddie S Solo; Joseph Y Chizimu; Jeewan Thapa; Kyoko Hayashida; Bernard M Hang'ombe; Musso Munyeme; Aki Tamaru; Takayuki Wada; Shiomi Yoshida; Takuya Kodera; Mistuo Kawase; Stephen V Gordon; Keiko Yamada; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, 13, 6, e0242124, 2025年06月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, UNLABELLED: Although human tuberculosis (TB) caused by Mycobacterium bovis is clinically, pathologically, and radiologically indistinguishable from Mycobacterium tuberculosis-caused TB, M. bovis is innately resistant to pyrazinamide, a key first-line drug effective against M. tuberculosis. The rapid differentiation of these two biovars is therefore of high clinical and epidemiologic importance. Most current molecular tools in resource-limited settings identify mycobacteria only to the M. tuberculosis species (MTB) level. In this study, we report a multiplex loop-mediated isothermal amplification (LAMP) method coupled with dipstick chromatography for the rapid and easy differential detection of M. bovis and M. tuberculosis. The assay was optimized and validated using 143 isolates comprising six MTB reference strains, 50 M. bovis isolates, 58 M. tuberculosis isolates, 24 non-tuberculous mycobacterial (NTM) strains, and five other respiratory pathogens. The multiplex LAMP correctly detected MTB and distinguished between M. tuberculosis and M. bovis simultaneously with sensitivities of 500 fg and 1 pg DNA, respectively, within 60 min, and the results were visualized by dipstick chromatography within 10 min. The assay was specific in that no major respiratory pathogens tested, including NTM strains, were positive. The multiplex dipstick LAMP assay is therefore a useful and accurate low-cost method for the differential identification of M. bovis and M. tuberculosis, especially in endemic areas where bovine and human TB coexist. The distinction between M. bovis and M. tuberculosis can also aid in monitoring the spread of M. bovis to humans and allow for correct treatment, which will ultimately contribute to TB control in both humans and animals. IMPORTANCE: Human tuberculosis caused by Mycobacterium tuberculosis and Mycobacterium bovis shows similar clinical symptoms; however, the treatment differs because M. bovis is inherently resistant to pyrazinamide, a key first-line drug effective against M. tuberculosis. Most available molecular tools cannot distinguish the two biovars. This study addresses this gap by introducing a multiplex loop-mediated isothermal amplification (LAMP) method coupled with dipstick chromatography that can simultaneously and differentially detect M. bovis and M. tuberculosis within 60 min. The LAMP method does not require sophisticated high-cost equipment and can be easily implemented in resource-limited settings. Our LAMP facilitates rapid and accurate tuberculosis diagnosis, enabling appropriate therapeutic agents to be selected in areas where bovine and human tuberculosis coexist. It can also screen for M. bovis infection in humans and livestock, providing prevalence data in areas where such information is lacking.
• ARNAX is an ideal adjuvant for COVID-19 vaccines to enhance antigen-specific CD4+ and CD8+ T-cell responses and neutralizing antibody induction.
  Tomomi Kawakita; Toshiki Sekiya; Yayoi Kameda; Naoki Nomura; Marumi Ohno; Chimuka Handabile; Akari Yamaya; Hideo Fukuhara; Yuki Anraku; Shunsuke Kita; Shinsuke Toba; Hirotake Tsukamoto; Tomohiro Sawa; Hiroyuki Oshiumi; Yasushi Itoh; Katsumi Maenaka; Akihiko Sato; Hirofumi Sawa; Yasuhiko Suzuki; Lorena E Brown; David C Jackson; Hiroshi Kida; Misako Matsumoto; Tsukasa Seya; Masashi Shingai
  Journal of virology, 99, 5, e0229024, 2025年05月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, UNLABELLED: ARNAX is a synthetic nucleotide-based Toll-like receptor 3 (TLR3) ligand that specifically stimulates the TLR3/TIR domain-containing adaptor molecule 1 (TICAM-1) pathway without activating inflammatory responses. ARNAX activates cellular immunity via cross-presentation; hence, its practical application has been demonstrated in cancer immunotherapy. Given the importance of cellular immunity in virus infections, ARNAX is expected to be a more effective vaccine adjuvant for virus infections than alum, an adjuvant approved for human use that mainly enhances humoral immunity. In the present study, the trimeric recombinant spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was prepared as a vaccine antigen and formulated with ARNAX. When T-cell and neutralizing antibody responses were evaluated in immunized mice, antigen formulated with ARNAX generated significantly larger numbers of antigenspecific CD4+ and CD8+ T cells, as well as higher titers of neutralizing antibodies, compared to antigen alone or antigen formulated with alum. In experiments where immunized mice were challenged with a SARS-CoV-2 mouse-adapted virus derived from the ancestral strain, immunization with antigen formulated with ARNAX reduced virus titers in the lungs at 3 days post-infection to a much greater extent than did immunization with either antigen alone or that formulated with alum. These results show that ARNAX potently enhances the levels of both cellular and humoral immunity above those seen with alum, providing significantly greater viral clearing responses. Thus, ARNAX may act as a useful adjuvant for prophylactic vaccines, particularly for viral infectious diseases. IMPORTANCE: Cellular immunity is a critical immunological defense system against virus infections. However, aluminum salts, the most widely used adjuvant for vaccines for human use, do not promote strong cellular immunity. To prepare for the next pandemic of viral origin, the development of Th1-type adjuvants with low adverse reactions that induce cellular immunity is necessary. ARNAX is a TLR3 agonist consisting of DNA-RNA hybrid nucleic acid, which is expected to be an adjuvant that induces cellular immunity. The present study using a coronavirus disease 2019 mouse model demonstrated that ARNAX potently induces cellular immunity in addition to humoral immunity with minimal induction of inflammatory cytokines. Therefore, ARNAX has the potential to be used as a potent and welltolerated adjuvant for vaccines against pandemic viruses emerging in the future.
• Antimicrobial susceptibility and genetic diversity of staphylococcus pseudintermedius isolated from companion animals and human clinical patients in Japan: Potential zoonotic implications.
  Masaru Usui; Rana Fahmi Sabala; Sawa Morita; Akira Fukuda; Yuzo Tsuyuki; Kae Torii; Yuka Nakamura; Koichi Okamura; Tadato Komatsu; Junpei Sasaki; Chie Nakajima; Yasuhiko Suzuki
  Journal of global antimicrobial resistance, 42, 66, 72, 2025年05月, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Staphylococcus pseudintermedius is the primary pathogen that causes pyoderma in companion animals. The increasing number of multidrug-resistant strains, including methicillin-resistant S. pseudintermedius (MRSP), has become a major concern, highlighting the need for comprehensive data on antimicrobial susceptibility. Furthermore, with advancements in the accurate identification of S. pseudintermedius in human clinical patients, it is imperative to elucidate its definitive zoonotic potential. METHODS: We analyzed 111 strains of S. pseudintermedius derived from companion animals and 21 strains of S. pseudintermedius from human clinical patients to clarify antimicrobial susceptibility and correlation between strains derived from companion animals and humans. RESULTS: Approximately half of the animal-derived S. pseudintermedius isolates were MRSP. The isolates, particularly MRSP, exhibited high resistance to multiple antimicrobials used to treat pyoderma. Although florfenicol and fusidic acid are not approved for the treatment of pyoderma in companion animals in Japan, their efficacy has been demonstrated. Genetic analysis revealed that ST121, ST45, and ST71 were the most common ST types in animals. Additionally, ten novel STs were identified. ST45 and ST71 have frequently been identified in companion animals abroad, suggesting potential international transmission. However, ST121 has rarely been reported outside Japan, indicating its unique evolutionary trajectory within the country. Furthermore, these sequence types were identified in strains isolated from humans. Core genome analysis revealed nearly identical genotypes, suggesting transmission from companion animals to humans. CONCLUSION: A limited number of approved antimicrobials are effective against S. pseudintermedius (particularly MRSP), which is being transmitted as a zoonotic infection from companion animals to humans.
• Development of a PCR-dipstick DNA chromatography-based tool for the detection of CTX-M- and TEM-producing Escherichia coli and Klebsiella pneumoniae isolated from patients in Kafue and Katete districts of Zambia.
  Misheck Shawa; Kyoko Hayashida; Naganori Nao; Atmika Paudel; Harvey Kamboyi; Herman Chambaro; Malala Mulavu; Cynthia Sipho Khumalo; Mike Nundwe; Tuvshinzaya Zorigt; Chinatsu Nakamura; Yongjin Qiu; Naoko Kawai; Maisa Kasanga; Joseph Chizimu; Lavel Moonga; Joseph Ndebe; Manyando Simbotwe; Shohei Ogata; Mulemba Samutela; Chie Nakajima; Roma Chilengi; Mable Mutengo; Masahiro Kajihara; Hirofumi Sawa; Bernard Hang'ombe; Yasuhiko Suzuki; Hideaki Higashi
  BMC infectious diseases, 25, 1, 541, 541, 2025年04月16日, ［国際誌］
  英語, 研究論文（学術雑誌）, In Zambia, 40% of clinical Gram-negative bacteria are either Escherichia coli or Klebsiella pneumoniae, with a high third-generation cephalosporin (3GC) resistance prevalence. Therefore, 3GC resistance surveillance is a crucial indicator for guiding focused intervention policies. However, the lack of genotypic diagnostic tools limits the ability to elucidate trends, especially in peri-urban and rural areas of developing countries. This study aimed to develop a rapid, cost-effective tool for the genotypic surveillance of 3GC resistance. Here, 900 stool samples collected from patients in Kafue (peri-urban, n = 400) and Katete (rural, n = 500) districts of Zambia were used for bacterial isolation on MacConkey agar supplemented with 1 μg/ml cefotaxime. Isolated 3GC-resistant strains were characterized by sequencing the 16S rRNA gene and screening for blaCTX-M and blaTEM genes using single polymerase chain reaction (PCR). Furthermore, selected 3GC-resistant strains were subjected to whole-genome sequencing (WGS) using MiSeq/HiSeq (n = 34) and MinION (n = 1). Using the data from this and other previous studies, we developed a rapid PCR-dipstick DNA chromatography-based tool for detecting blaCTX-M, blaTEM, E. coli-specific yaiO, and K. pneumoniae-specific khe genes. The prevalence of isolated 3GC resistant strains was 15.4% (139/900), dominated by E. coli (102/139, 73.4%). On PCR, the blaCTX-M gene was detected in 72.7% (101/139) of the isolates, while blaTEM was found in 46.8% (65/139) of the strains. The developed tool displayed a high level of agreement with WGS and single PCR/Sanger sequencing, with sensitivity and specificity ≥ 95% and Kappa ≥ 0.95 for each of the four target genes. We envisage that the simplicity and adaptability of this tool will be a significant advantage for the surveillance of 3GC resistance in Zambia and elsewhere.
• Antimicrobial Resistance Patterns and Serological Diversity of Shigella Species from Patient Isolates at University Teaching Hospital in Lusaka, Zambia
  Mike Nundwe; Joseph Yamweka Chizimu; John Mwaba; Misheck Shawa; Rodrick S. Katete; Mable Mwale Mutengo; Ruth Nakazwe; Namwiinga R. Mulunda; Cephas Sialubanje; Mox Malama Kalumbi; Yamba Kaunda; Rapheal Chanda; Herman Chambaro; Harvey K. Kamboyi; Thoko Kapalamula; Steward Mudenda; Freeman W. Chabala; Bernard M. Hang’ombe; Roma Chilengi; Chie Nakajima; Yasuhiko Suzuki
  Bacteria, 4, 2, 18, 18, MDPI AG, 2025年04月02日
  研究論文（学術雑誌）, Background: Shigella species are the leading cause of human shigellosis. In Zambia, more than 30% of children experiencing diarrhea are infected with Shigella species. The increasing resistance of Shigella species to the recommended therapy is of great concern. Therefore, this study investigated the antibiotic resistance profiles and phenotypic and genotypic characteristics of Shigella isolates at the largest referral hospital in Zambia. Methodology: Of the forty-eight archived presumptive Shigella isolates, thirty-two were serologically confirmed and subjected to antimicrobial susceptibility testing using the Kirby Bauer disk diffusion method. Thereafter, polymerase chain reaction was performed to detect the bla genes. Results: Most isolates were Shigella flexneri (16/32, 50%) and Shigella sonnei (14/32, 44%), while Shigella boydii and Shigella dysenteriae were rare. High resistance rates were noted for sulfamethoxazole/trimethoprim (78%) and tetracycline (75%), while 15.6% of the isolates showed resistance to ciprofloxacin and/or azithromycin. The blaTEM gene encoding beta-lactamase was detected in 7/32 (22%) of isolates. Conclusions: In this study, a significant number of multidrug-resistant isolates were identified. Additionally, Shigella species resistant to the World Health Organization-recommended drugs call for strengthened laboratory diagnosis and close monitoring of these pathogens to guide the clinical management of shigellosis.
• 国境を越えて:留学生・ポスドクの挑戦 2016年から2020年までのタイの運河水におけるSalmonellaの遺伝的多様性と抗菌薬耐性(Beyond Borders: Challenges for International Students and Postdocs Genetic diversity and antimicrobial resistance of Salmonella in Thai canal water from 2016 to 2020)
  Toyting Jirachaya; 佐藤 豊孝; Supha Neunghatai; Thongpanich Yuwanda; 堀内 基広; Thapa Jeewan; 中島 千絵; 鈴木 定彦; Utrarachkij Fuangfa
  日本細菌学雑誌, 80, 2, 34, 34, 日本細菌学会, 2025年04月
  英語
• ライ菌のDNAジャイレースの温度と活性の関係に関する解析(Analysis of the relationship between temperature and activity of Mycobacterium leprae DNA gyrase)
  八代 龍; 金 玄; Suwanthada Pondpan; Poussier Chariotte; 中島 千絵; 鈴木 定彦; 阿戸 学; 中田 登
  日本細菌学雑誌, 80, 2, 107, 107, 日本細菌学会, 2025年04月
  英語
• 国境を越えて:留学生・ポスドクの挑戦 2016年から2020年までのタイの運河水におけるSalmonellaの遺伝的多様性と抗菌薬耐性(Beyond Borders: Challenges for International Students and Postdocs Genetic diversity and antimicrobial resistance of Salmonella in Thai canal water from 2016 to 2020)
  Toyting Jirachaya; 佐藤 豊孝; Supha Neunghatai; Thongpanich Yuwanda; 堀内 基広; Thapa Jeewan; 中島 千絵; 鈴木 定彦; Utrarachkij Fuangfa
  日本細菌学雑誌, 80, 2, 34, 34, 日本細菌学会, 2025年04月
  英語
• Mycobacterium shinjukuenseにおける遺伝的多様性とゲノム安定性
  和田 崇之; 井上 陽晴; 吉田 志緒美; 村瀬 良朗; 中島 千絵; 鈴木 定彦; 御手洗 聡; 福島 由華理
  日本細菌学雑誌, 80, 2, 88, 88, 日本細菌学会, 2025年04月
  日本語
• ライ菌のDNAジャイレースの温度と活性の関係に関する解析(Analysis of the relationship between temperature and activity of Mycobacterium leprae DNA gyrase)
  八代 龍; 金 玄; Suwanthada Pondpan; Poussier Chariotte; 中島 千絵; 鈴木 定彦; 阿戸 学; 中田 登
  日本細菌学雑誌, 80, 2, 107, 107, 日本細菌学会, 2025年04月
  英語
• Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae.
  Kojiro Uemura; Toyotaka Sato; Soh Yamamoto; Noriko Ogasawara; Jirachaya Toyting; Kotaro Aoki; Akira Takasawa; Masayuki Koyama; Atsushi Saito; Takayuki Wada; Kaho Okada; Yurie Yoshida; Koji Kuronuma; Chie Nakajima; Yasuhiko Suzuki; Motohiro Horiuchi; Kenichi Takano; Satoshi Takahashi; Hirofumi Chiba; Shin-Ichi Yokota
  Nature communications, 16, 1, 2917, 2917, 2025年03月25日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bacteria continually evolve. Previous studies have evaluated bacterial evolution in retrospect, but this approach is based on only speculation. Cohort studies are reliable but require a long duration. Additionally, identifying which genetic mutations that have emerged during bacterial evolution possess functions of interest to researchers is an exceptionally challenging task. Here, we establish a Rapid and Integrated Bacterial Evolution Analysis (RIBEA) based on serial passaging experiments using hypermutable strains, whole-genome and transposon-directed sequencing, and in vivo evaluations to monitor bacterial evolution in a cohort for one month. RIBEA reveals bacterial factors contributing to serum and antimicrobial resistance by identifying gene mutations that occurred during evolution in the major respiratory pathogen Klebsiella pneumoniae. RIBEA also enables the evaluation of the risk for the progression and the development of invasive ability from the lung to blood and antimicrobial resistance. Our results demonstrate that RIBEA enables the observation of bacterial evolution and the prediction and identification of clinically relevant high-risk bacterial strains, clarifying the associated pathogenicity and the development of antimicrobial resistance at genetic mutation level.
• A novel ready-to-use loop-mediated isothermal amplification (LAMP) method for detection of Burkholderia mallei and B. pseudomallei.
  Mitsuru Nakase; Jeewan Thapa; Vanaabaatar Batbaatar; Ochirbat Khurtsbaatar; Batchuluun Enkhtuul; Jugderkhorloo Unenbat; Baasansuren Lkham; Sachiho Fujita; Ai Koshikawa; Apichai Tuanyok; Vannarat Saechan; Hideaki Higashi; Kyoko Hayashida; Yasuhiko Suzuki; Chie Nakajima; Takashi Kimura
  BMC microbiology, 25, 1, 36, 36, 2025年01月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Glanders and melioidosis are contagious zoonotic diseases caused by Burkholderia mallei and B. pseudomallei, respectively. Bacterial isolation and polymerase chain reaction (PCR) have been used to detect these bacteria in animals suspected of infection; however, both methods require skilled experimental techniques and expensive equipment. These obstacles make it difficult to diagnose B. mallei and B. pseudomallei infections in areas where reagents and equipment are difficult to procure. To solve this problem, we developed an easy and ready-to-use dried-format diagnostic tool based on loop-mediated isothermal amplification (LAMP) method. RESULTS: The primer set targeting the internal transcribed spacer (ITS) region detected 10 genomic copies of B. mallei DNA and B. pseudomallei DNA using the conventional liquid LAMP method. This primer set did not detect any other Burkholderia species. Using this novel primer set, a dried-format in-house LAMP method with high sensitivity and specificity was developed. This method was used to test for the presence of B. mallei DNA in swabs collected from the nasal cavity and ulcerated skin of 19 B. mallei-infected horses and five uninfected horses and was compared with the real-time PCR method. These two tests showed 87.5% agreement for the positive samples and 100% agreement for the negative samples. This method detected all tested B. pseudomallei clinical isolates. CONCLUSIONS: We established the first dry LAMP method for the detection of B. mallei and B. pseudomallei. This study provided a simple, rapid, cost-effective, and sensitive diagnostic tool for glanders and melioidosis.
• Unification of symbiotic bacteria during larva-to-adult transition in Culicoides circumscriptus (Diptera: Ceratopogonidae).
  Ryo Ozuru; Junya Yamagishi; Ayumi Takeuchi; Yusuke Date; Takatoshi Fujii; Chihiro Sugimoto; Chie Nakajima; Yasuhiko Suzuki; Kaoru Aoki; Jun Fujii; Takashi Matsuba
  FEMS microbiology letters, 372, 2025年01月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, Blood-sucking midges such as Leptoconops and Culicoides are of medical importance due to their role in causing skin irritation and potentially transmitting pathogens. Investigating their bacterial communities, including possible endosymbionts, may help clarify ecological adaptations and interactions with hosts. Leptoconops nipponensis Tokunaga (Lnt) and Culicoides circumscriptus (Cc), blood-sucking midges, cause severe itching and inflammation in humans. Cc was collected from a small sample of an outbreak swarm of Lnt in the peninsula area of Yonago City, Tottori Prefecture, Japan. This study compared the bacterial flora of Lnt and Cc, revealing distinct bacterial diversity shifts in these insect species between life stages. We analyzed the bacterial communities of adult and larval females of Cc and Lnt using MiSeq sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. Notably, alpha diversity in Cc adults was significantly reduced to 1.5 (n = 43), indicating that Cc adults were dominated by a single bacterial genus, compared to 14.9 in Cc larvae (n = 19). BLAST (Basic Local Alignment Search Tool) analysis identified this dominant genus in adult Cc as Rickettsia (Candidatus Tisiphisa), which is known for transovarial transmission in arthropod vectors. In contrast, the bacterial diversity of Lnt showed no significant difference between adults (18.1, n = 32) and larvae (n = 15). These findings suggest that the dominance of Rickettsia in Cc (Candidatus Tisiphisa) adults is linked to their emergence, potentially reflecting differences in reproductive biology and ecological adaptations between these two insect species. Further research is needed to elucidate the functional role of Rickettsia in the life cycle and physiology of Cc.
• Surveillance of Escherichia coli From Frozen Chicken Meat in Fiji: Resistance Characteristics and Public Health Concerns.
  Deepika Darshani Lata; Rana Fahmi Sabala; Akira Fukuda; Chie Nakajima; Yasuhiko Suzuki; Masaru Usui; Muhammad Asif Zahoor
  International journal of food science, 2025, 1, 5487064, 5487064, Wiley, 2025年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, Antimicrobial resistance (AMR) is a growing concern in human and veterinary medicine. Misuse and overuse of antimicrobials in human medicine, veterinary medicine, agriculture, and aquaculture are major drivers of AMR development, with resistant bacteria also being selected in livestock and transmitted through meat. Research on AMR in livestock and animal‐derived foods is lacking in Fiji; thus, the associated risks remain unclear. Chicken is widely consumed in Fiji and is predominantly served frozen. This study is aimed at determining the prevalence and resistance profiles of Escherichia coli in frozen chicken meat from Fijian supermarkets. A total of 100 frozen chicken meat samples were purchased from supermarkets and retail outlets in Fiji for this study. E. coli was isolated from 72% of the samples. The E. coli isolates showed relatively high levels of resistance to ampicillin (36%), tetracycline (24%), and streptomycin (17%). Only one cefotaxime‐resistant isolate was obtained, which was identified as an extended‐spectrum β ‐lactamase (ESBL)–producing bacterium. This isolate harbored the ESBL‐producing gene bla _CTX-M-1 and was classified as ST2522. One colistin‐resistant isolate was obtained, and its resistance was attributed to a chromosomal mutation in the pmrB gene. The high level of intestinal bacterial contamination in frozen chicken meat suggests that improved hygiene management is necessary throughout the production and distribution chains. Furthermore, because resistance to antimicrobials is important in both human and veterinary medicine (cefotaxime‐ and colistin‐resistant E. coli ), careful monitoring of AMR trends in Fiji is essential. These results suggest that AMR surveillance in meat and livestock is necessary to prevent its spread in Fiji.
• In silico characterization of chromosomally integrated blaCTX-M genes among clinical Enterobacteriaceae in Africa: insights from whole-genome analysis.
  Misheck Shawa; Herman Chambaro; Harvey K Kamboyi; Clement Sulwe; Joseph Y Chizimu; Situmbeko J Nasilele; Shohei Ogata; Mulemba Samutela; Tuvshinzaya Zorigt; Steward Mudenda; Manyando Simbotwe; Mwamba Nsofwa; Jedidiah Chanda; Freeman Chabala; Mike Nundwe; Joseph Ndebe; Msangwa Sinjani; Kyoko Hayashida; Naganori Nao; Roma Chilengi; Hirofumi Sawa; Yasuhiko Suzuki; Bernard Hang'ombe; Masahiro Kajihara; Hideaki Higashi
  Frontiers in microbiology, 16, 1655907, 1655907, Frontiers Media SA, 2025年09月12日, ［国際誌］
  英語, 研究論文（学術雑誌）, Antimicrobial resistance (AMR) mediated by extended-spectrum β-lactamases (ESBLs) is a growing global concern, particularly among Enterobacteriaceae. The CTX-M-type ESBLs, encoded by the bla_CTX-M gene, are of significant public health importance due to their high prevalence and broad geographic distribution. Typically located on plasmids and often co-occurring with other AMR genes, bla_CTX-M contributes to multidrug resistance (MDR). However, increasing evidence suggests secondary chromosomal integration of bla_CTX-M, sometimes alongside other resistance determinants. The extent and implications of this mechanism remain poorly characterized, especially in Africa, where genomic surveillance is limited. In this study, we retrieved 295 chromosomal sequences of Enterobacteriaceae of African origin from the GenBank and performed in silico predictions of bla_CTX-M and other AMR genes. bla_CTX-M-carrying sequences were further characterized by in silico multilocus sequence typing and genome annotation. Chromosomal insertions were identified through alignment with reference genomes. Overall, 47 of 295 sequences (15.9%) harbored the bla_CTX-M gene, with the highest prevalence in Klebsiella pneumoniae (29/157, 18.5%), followed by Escherichia coli (13/72, 18.1%), Enterobacter spp. (4/38, 10.5%), and Shigella spp. (1/12, 8.3%). The most common allele was bla_CTX-M-15 (31/47, 66.0%), followed by bla_CTX-M-14 (12/47, 25.5%), bla_CTX-M-55 (3/47, 6.4%), and bla_CTX-M-27 (1/27, 3.7%). Co-occurrence of bla_CTX-M with additional AMR genes was frequently observed, with integration events often associated with mobile genetic elements such as ISEcp1 and IS26. Notably, strains from the same hospital setting were phylogenetically related and shared sequence types and AMR gene profiles, suggesting local clonal dissemination. These findings reveal a notable presence of chromosomally integrated bla_CTX-M among African Enterobacteriaceae, frequently in association with other resistance genes, thereby facilitating stable MDR propagation independent of plasmid maintenance. This evolutionary adaptation may have significant implications for the persistence and spread of MDR in clinical settings.
• Evaluating infection prevention and control programs in Zambian hospitals using the WHO infection prevention and control assessment framework tool.
  Steward Mudenda; Joseph Yamweka Chizimu; Linus Ndegwa; Maisa Kasanga; Ilunga Mutwale; Aubrey Chichonyi Kalungia; Evelyn Wesangula; Adriano Focus Lubanga; James C L Mwansa; Martha Mwaba; Amos Yared Massele; Nyambe Sinyange; Tapfumanei Mashe; Malambo Mutila; Paul Simujayang'ombe; David Lowrance; Kaunda Yamba; Misheck Shawa; Chie Nakajima; Yasuhiko Suzuki; John Bwalya Muma; Massimo Sartelli; Brian Godman; Roma Chilengi
  Frontiers in public health, 13, 1642119, 1642119, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Infection Prevention and Control (IPC) is key to preventing healthcare-associated infections (HAIs) and the spread of antimicrobial resistance (AMR). This study evaluated the implementation of IPC in Zambian hospitals. MATERIALS AND METHODS: We conducted a multicentric cross-sectional study in nine hospitals across Zambia using the WHO IPCAF tool. Data were collected from September 1 to 30, 2024 and analyzed using the self-scoring Excel and IBM SPSS version 25.0. RESULTS: Out of the nine hospitals assessed, four were tertiary-level hospitals while the rest were secondary-level hospitals. Overall, the implementation of IPC core components was intermediate (IPCAF Score of 594 out of 800). Four hospitals had IPCAF scores between 401 and 600, indicating an intermediate level of IPC implementation. Five hospitals scored between 601 and 800, indicating an advanced implementation of IPC in these hospitals. Three tertiary hospitals scored between 601 and 800, demonstrating their advanced implementation of IPC core components. CONCLUSION: This study found that the overall implementation of IPC in the surveyed hospitals was intermediate, indicating that further improvements were needed. There is a need to provide peer-learning support and strengthen IPC implementation to respond to new or re-emerging infections and AMR in the country and beyond.
• Development of caninized anti-CTLA-4 antibody as salvage combination therapy for anti-PD-L1 refractory tumors in dogs.
  Naoya Maekawa; Satoru Konnai; Kei Watari; Hiroto Takeuchi; Takeshi Nakanishi; Taro Tachibana; Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Ryo Owaki; Madoka Yokokawa; Yumiko Kagawa; Satoshi Takagi; Tatsuya Deguchi; Hiroshi Ohta; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
  Frontiers in immunology, 16, 1570717, 1570717, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy; however, the clinical efficacy of anti-PD-1/PD-L1 monotherapy is generally limited, highlighting the need to develop combination therapies. Dogs develop spontaneous tumors in immunocompetent settings, and anti-PD-1/PD-L1 antibodies exert similar clinical benefits. However, no clinically relevant anti-CTLA-4 antibody has been reported, limiting the value of canine tumors as comparative models for human ICI research. Here, canine CTLA-4 was molecularly characterized, and a caninized anti-CTLA-4 antibody (ca1C5) that blocks CTLA-4/ligand binding was developed. Treatment with ca1C5 increased cytokine production in canine immune cell cultures, and the immunostimulatory effect was enhanced when used in combination with the anti-PD-L1 antibody c4G12. As a proof-of-concept, a veterinary clinical study was conducted to demonstrate the safety and clinical efficacy of anti-CTLA-4 antibody as salvage combination therapy in dogs with advanced tumors refractory to prior c4G12 monotherapy. The combination treatment (c4G12 plus ca1C5) was well-tolerated, and evidence of antitumor activity was observed in one dog with oral malignant melanoma. Further studies are warranted to advance veterinary care for dogs and to better characterize canine ICI models for human onco-immunology research.
• Spreading Ability of Tet(X)-Harboring Plasmid and Effect of Tetracyclines as a Selective Pressure.
  Akira Fukuda; Yuta Kozaki; Cemil Kürekci; Yasuhiko Suzuki; Chie Nakajima; Masaru Usui
  Microbial drug resistance (Larchmont, N.Y.), 30, 12, 489, 501, 2024年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, Tigecycline is a last-resort antimicrobial in humans. Tetracyclines are the most widely used antimicrobials in livestock. Mobile tigecycline resistance genes [tet(X)] are disseminated worldwide, and tetracycline use may have promoted the selection of tet(X) genes. Thus, the selective pressure on tet(X) genes and their plasmids in livestock must be elucidated. We performed a retrospective study to clarify the prevalence of tigecycline-resistant Escherichia coli from pigs in Thailand. Screening for tigecycline resistance was performed on 107 E. coli strains from 25 samples, and tet(X)-carrying plasmids were characterized. tet(X) genes were cloned and expressed in E. coli. Bacterial growth rate in the presence of tetracycline as a result of the presence of tet(X) genes was also evaluated. Thirty-two tet(X4)-harboring tigecycline-resistant E. coli strains were detected in 10/25 samples (40%). The tet(X4) genes were carried on various Inc-type plasmids and flanked by ISCR2. The tet(X)-carrying plasmids were transferred to E. coli and Klebsiella pneumoniae. Acquisition of tet(X) genes and their plasmids improved bacterial growth in the presence of tetracycline. In summary, tetracycline use exerts selective pressure on tet(X) genes and their various backbone plasmids; therefore, a reduced amount of tetracycline use is important to limit the spreading of tet(X) genes.
• Vermicomposting reduces the antimicrobial resistance in livestock waste
  Masaru Usui; Akira Fukuda; Takashi Azuma; Yoshihiro Kobae; Yuichi Hori; Mitsutaka Kushima; Satoshi Katada; Chie Nakajima; Yasuhiko Suzuki
  Journal of Hazardous Materials Advances, 16, 2024年11月
  研究論文（学術雑誌）
• Antibiotic use and adherence to the WHO AWaRe guidelines across 16 hospitals in Zambia: a point prevalence survey.
  Joseph Yamweka Chizimu; Steward Mudenda; Kaunda Yamba; Chileshe Lukwesa; Raphael Chanda; Ruth Nakazwe; Misheck Shawa; Herman Chambaro; Harvey K Kamboyi; Aubrey Chichonyi Kalungia; Duncan Chanda; Sombo Fwoloshi; Elimas Jere; Tiza Mufune; Derick Munkombwe; Peter Lisulo; Tebuho Mateele; Jeewan Thapa; Kenneth Kapolowe; Nyambe Sinyange; Cephas Sialubanje; Nathan Kapata; Mirfin Mpundu; Freddie Masaninga; Khalid Azam; Chie Nakajima; Makomani Siyanga; Nathan Nsubuga Bakyaita; Evelyn Wesangula; Martin Matu; Yasuhiko Suzuki; Roma Chilengi
  JAC-antimicrobial resistance, 6, 5, dlae170, 2024年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The inappropriate use of antibiotics in hospitals contributes to the development and spread of antimicrobial resistance (AMR). This study evaluated the prevalence of antibiotic use and adherence to the World Health Organization (WHO) Access, Watch and Reserve (AWaRe) classification of antibiotics across 16 hospitals in Zambia. METHODS: A descriptive, cross-sectional study employing the WHO Point Prevalence Survey (PPS) methodology and WHO AWaRe classification of antibiotics was conducted among inpatients across 16 hospitals in December 2023, Zambia. Data analysis was performed using STATA version 17.0. RESULTS: Of the 1296 inpatients surveyed in the 16 hospitals, 56% were female, and 54% were aged between 16 and 50 years. The overall prevalence of antibiotic use was 70%. Additionally, 52% of the inpatients received Watch group antibiotics, with ceftriaxone being the most prescribed antibiotic. Slightly below half (48%) of the inpatients received Access group antibiotics. Compliance with the local treatment guidelines was 53%. CONCLUSIONS: This study found a high prevalence of prescribing and use of antibiotics in hospitalized patients across the surveyed hospitals in Zambia. The high use of Watch group antibiotics was above the recommended threshold indicating non-adherence to the WHO AWaRe guidelines for antibiotic use. Hence, there is a need to establish and strengthen antimicrobial stewardship programmes that promote the rational use of antibiotics in hospitals in Zambia.
• WQ-3810, a fluoroquinolone with difluoropyridine derivative as the R1 group exerts high potency against quinolone-resistant Campylobacter jejuni.
  Kentaro Koide; Hyun Kim; Matthew V X Whelan; Lawrence P Belotindos; Wimonrat Tanomsridachchai; Ruchirada Changkwanyeun; Masaru Usui; Tadhg Ó Cróinín; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, 12, 10, e0432223, 2024年08月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, UNLABELLED: Quinolone-resistant Campylobacter jejuni have been increasing worldwide. Quinolones exert their antibacterial activity by inhibiting DNA gyrase, but most of the isolates acquire quinolone resistance via an amino acid substitution in the A subunit of DNA gyrase. WQ-3810 is a quinolone antibiotic that has been reported to have high potency even to DNA gyrase with amino acid substitutions in several bacterial species; however, there was no information on C. jejuni. Hence, this study aimed to evaluate the activity of WQ-3810 to inhibit wild-type/mutant DNA gyrases of C. jejuni and the bacterial growth for accessing the potency for the treatment of quinolone-resistant C. jejuni infection. The inhibitory activity of WQ-3810 was assessed and compared with ciprofloxacin and nalidixic acid by calculating the half maximal inhibitory concentration (IC50) against wild-type/mutant DNA gyrases. Next, the minimum inhibitory concentration (MIC) of WQ-3810 and five other quinolones was determined for C. jejuni including quinolone-resistant strains with amino acid substitutions in GyrA. Furthermore, the interaction between WQ-3810 and wild-type/mutant DNA gyrase was speculated using docking simulations. The IC50 of WQ-3810 against wild-type DNA gyrase was 1.03 µg/mL and not different from that of ciprofloxacin. However, those of WQ-3810 against mutant DNA gyrases were much lower than ciprofloxacin. The MICs of WQ-3810 ranged <0.016-0.031 µg/mL and were the lowest against both quinolone-susceptible and quinolone-resistant strains among the examined quinolones. The results obtained by the docking simulation agreed well with this observation. WQ-3810 seems to be a promising antimicrobial agent for the infections caused by quinolone-resistant C. jejuni. IMPORTANCE: WQ-3810, a relatively new quinolone antibiotic, demonstrates exceptional antibacterial properties against certain pathogens in previous studies. However, its efficacy against quinolone-resistant Campylobacter jejuni was not previously reported. The prevalence of quinolone-resistant C. jejuni as a cause of foodborne illnesses is increasing, prompting this investigation into the effectiveness of WQ-3810 as a countermeasure. This study revealed high inhibitory activity of WQ-3810 against both wild-type and mutant DNA gyrases of C. jejuni. WQ-3810 was equally efficacious as ciprofloxacin against wild-type DNA gyrases but showed superior effectiveness against mutant DNA gyrases. WQ-3810 also demonstrated the lowest minimum inhibitory concentrations, highlighting its enhanced potency against both susceptible and resistant strains of C. jejuni. This observation was well supported by the results of the in silico analysis. Consequently, WQ-3810 exhibits a higher level of bactericidal activity compared to existing quinolones in combating both susceptible and resistant C. jejuni isolates.
• Interplay between Amino Acid Substitution in GyrA and QnrB19: Elevating Fluoroquinolone Resistance in Salmonella Typhimurium.
  Pondpan Suwanthada; Siriporn Kongsoi; Sasini Jayaweera; Mwangala Lonah Akapelwa; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  ACS infectious diseases, 10, 8, 2785, 2794, 2024年08月09日, ［国際誌］
  英語, 研究論文（学術雑誌）, Globally, there have been increasing reports of antimicrobial resistance in nontyphoidal Salmonella (NTS), which can develop into severe and potentially life-threatening diarrhea. This study focuses on the synergistic effects of DNA gyrase mutations and plasmid-mediated quinolone resistance (PMQR) genes, specifically qnrB19, on fluoroquinolone (FQ) resistance in Salmonella Typhimurium. By utilizing recombinant mutants, GyrAS83F and GyrAD87N, and QnrB19's, we discovered a significant increase in fluoroquinolones resistance when QnrB19 is present. Specifically, ciprofloxacin and moxifloxacin's inhibitory concentrations rose 10- and 8-fold, respectively. QnrB19 was found to enhance the resistance capacity of mutant DNA gyrases, leading to high-level FQ resistance. Additionally, we observed that the ratio of QnrB19 to DNA gyrase played a critical role in determining whether QnrB19 could protect DNA gyrase against FQ inhibition. Our findings underscore the critical need to understand these resistance mechanisms, as their coexistence enables bacteria to withstand therapeutic FQ levels, posing a significant challenge to treatment efficacy.
• The first insight into Mycobacterium tuberculosis complex isolates in the lower northern region in Thailand.
  Janisara Rudeeaneksin; Supranee Bunchoo; Benjawan Phetsuksiri; Sopa Srisungngam; Ratchaneeporn Khummin; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Transactions of the Royal Society of Tropical Medicine and Hygiene, 118, 8, 527, 536, 2024年08月05日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Tuberculosis (TB) remains an important infectious disease and different genotypes have been reported. This study aimed to investigate the genetic diversity and molecular epidemiology of TB in the lower northern region of Thailand, where genotyping data are limited. METHODS: A total of 159 Mycobacterium tuberculosis complex (MTBC) isolates from this region were genotyped by spoligotyping and the major spoligotypes were further subdivided by the mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) method. RESULTS: Spoligotyping identified 34 types and classified them into 14 clusters. East African-Indian (EAI) groups were the most frequent (44.7%), followed by Beijing (36.5%), with a higher prevalence of drug resistance. By 15-loci MIRU-VNTR typing, the major groups of the Beijing and EAI2_NTB were further differentiated into 44 and 21 subtypes forming 9 and 5 subclusters with cluster rates of 0.26 and 0.44, respectively. The Hunter-Gaston Discriminatory Index among the Beijing and EAI2_NTB groups were 0.987 and 0.931, respectively, indicating high diversity. CONCLUSIONS: This is the first look at the MTBC genotypes in the lower northern region of Thailand, which could aid in understanding the distribution and potential spread of MTBC and Mycobacterium bovis in the target region to support TB control in Thailand.
• 比較ゲノム解析による乳牛由来黄色ブドウ球菌の国際的な拡散状況の解明
  大川 佳穂; 福田 昭; 米山 裕; 戸部 隆太; 中島 千絵; 鈴木 定彦; 臼井 優
  北海道獣医師会雑誌, 68, 8, 329, 329, (公社)北海道獣医師会, 2024年08月
  日本語
• Hyperthermophilic composting of livestock waste drastically reduces antimicrobial resistance
  Usui M; Azuma T; Katada S; Fukuda A; Suzuki Y; Nakajima C; Tamura Y
  Waste Management Bulletin, 2, 3, 241, 248, 2024年08月, ［査読有り］, ［招待有り］
  英語
• Epidemiology and molecular characterization of Mycobacterium tuberculosis including a drug-resistant strain associated with mortality of Asian elephants in Nepal 2019-2022.
  Arjun Pandit; Jeewan Thapa; Amir Sadaula; Yasuhiko Suzuki; Chie Nakajima; Susan K Mikota; Naresh Subedi; Bijaya Kumar Shrestha; Michito Shimozuru; Bhawana Shrestha; Bijendra Raya; Sanjay Chaudhary; Sarad Paudel; Toshio Tsubota
  Tuberculosis (Edinburgh, Scotland), 148, 102550, 102550, 2024年07月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, Tuberculosis (TB) is an emerging threat to the survival of elephants in Nepal. We investigated the lung tissue samples from nine elephants that died from 2019 to 2022 in Nepal using culture, conventional PCR, and loop-mediated isothermal amplification (LAMP) and then performed genotyping of five PCR-positive isolates to understand the possible transmission dynamics of Mycobacterium tuberculosis (Mtb). Results showed that two-thirds (6/9) of elephants were confirmed to be infected from Mtb by LAMP, 5/9 by PCR, and 4/9 by culture. Genotyping of Mtb isolates showed that elephants were infected with the Indo-Oceanic and Beijing lineages including an isoniazid-resistant Beijing lineage. MIRU-VNTR-based phylogeny, gyrA, and katG sequencing showed the possibility of ongoing transmission of Indo-Oceanic lineages and likely transmission of the drug-resistant Beijing lineage from human to elephant. Implementation of comprehensive surveillance and preventive measures are urgently needed to address this zoonotic disease and protect elephants from TB in Nepal.
• Correction: Narongpun et al. Whole-Genome Investigation of Zoonotic Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolated from Pigs and Humans in Thailand. Antibiotics 2023, 12, 1745.
  Pawarut Narongpun; Pattrarat Chanchaithong; Junya Yamagishi; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 13, 8, 2024年07月23日, ［国際誌］
  英語, In the published publication [...].
• Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system.
  Jose Maria Urtasun-Elizari; Ruoyao Ma; Hayleah Pickford; Damien Farrell; Gabriel Gonzalez; Viktor Perets; Chie Nakajima; Yasuhiko Suzuki; David E MacHugh; Apoorva Bhatt; Stephen V Gordon
  Tuberculosis (Edinburgh, Scotland), 148, 102544, 102544, 2024年07月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional. We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.
• WQ-3810: A Novel Fluoroquinolone Exhibiting Potency Against Fluoroquinolone-Resistant M.avium(タイトル和訳中)
  Jayaweera Sasini; Thapa Jeewan; Nakajima Chie; Suzuki Yasuhiko
  日本細菌学雑誌, 79, 2, 268, 268, 日本細菌学会, 2024年07月
  英語
• Biphasic Medium Using Nicotinamide for Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis.
  Waraporn Thuansuwan; Charoen Chuchottaworn; Chie Nakajima; Yasuhiko Suzuki; Nuntaree Chaichanawongsaroj
  Antibiotics (Basel, Switzerland), 13, 6, 2024年06月16日, ［国際誌］
  英語, 研究論文（学術雑誌）, Reliable drug susceptibility testing of pyrazinamide (PZA) is technically difficult, since PZA activity is pH sensitive. The aim of this study was to evaluate a biphasic medium assay (BMA) for the reliable detection of PZA resistance in Mycobacterium tuberculosis (MTB) using nicotinamide (NIC) as a surrogate for PZA and identifying the appropriate cut-off value for the assay. The PZA susceptibility of 122 multidrug-resistant tuberculosis (MDR-TB) isolates and 39 drug-susceptible tuberculosis (DS-TB) isolates was examined using the BMA with NIC at four different concentrations (250, 500, 1000, and 2000 mg/L) and comparing the results with results from the BACTEC MGIT 960 reference method. Out of 122 MDR-TB isolates, 40 were identified as resistant by the BACTEC MGIT 960 system, of which 92.5% contained mutations within their pncA gene plus promoter region. A minimum inhibitory concentration of NIC ≥ 1000 mg/L was used as the cut-off concentration to define resistance in correlation with the MGIT 960 outcomes. NIC-BMA had a sensitivity of 90.91%, a specificity of 100%, and an accuracy of 97.52% compared with the MGIT 960 method. NIC-BMA is a promising assay to screen PZA resistance in microbiological laboratories without automation or advanced molecular instruments.
• Wide distribution of plasmid mediated quinolone resistance gene, qnrS, among Salmonella spp. isolated from canal water in Thailand.
  Jirachaya Toyting; Neunghatai Supha; Yuwanda Thongpanich; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki; Fuangfa Utrarachkij
  Journal of applied microbiology, 135, 6, 2024年06月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, AIMS: This research focused on assessing the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants and antimicrobial susceptibility in Salmonella strains isolated from Thai canal water. METHODS AND RESULTS: From 2016 to 2020, 333 water samples were collected from six canals across Bangkok, Thailand. Salmonella spp. was isolated, PMQR genes were detected through polymerase chain reactions, and the antimicrobial susceptibility was examined using the disk diffusion method. The results indicated a 92.2% prevalence of Salmonella spp. in canal water, being serogroups B and C the most frequently detected. Overall, 35.3% of isolates harbored PMQR genes, being qnrS the most prevalent gene (97.2%, n = 137/141). Other PMQR genes, including qnrB, qnrD, oqxAB, and aac(6')-Ib-cr, were detected. Notably, six isolates harbored multiple PMQR genes. Furthermore, 9.3% and 3.8% of the overall isolates were resistant to nalidixic acid (NAL) and ciprofloxacin (CIP), respectively. PMQR-positive isolates showed higher rates of non-susceptibility to both NAL (48.2%, n = 68/141) and CIP (92.2%, n = 130/141) compared to PMQR-negative isolates (NAL: 8.9%, n = 23/258; CIP: 11.2%, n = 30/258). CONCLUSIONS: The high prevalence of Salmonella spp., significant PMQR-positive, and reduced susceptibility isolates in canal water is of public health concern in Bangkok.
• 日本の農場における家畜堆肥由来腸球菌の可動性リネゾリド耐性遺伝子(Mobile linezolid resistance genes in enterococci derived from livestock compost at Japanese farms)
  福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本細菌学雑誌, 79, 2, 121, 121, 日本細菌学会, 2024年06月
  英語
• タイ、バンコクの運河の水から分離されたサルモネラ菌のゲノム解析(Genomic Analysis of Salmonella Isolated from Canal Water in Bangkok, Thailand)
  Toyting Jirachaya; Nuanmuang Narong; Utrarachkij Fuangfa; Leekitcharoenphon Pimlapas; Aarestrup Frank; 佐藤 豊孝; Thapa Jeewan; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 79, 2, 128, 128, 日本細菌学会, 2024年06月
  英語
• Mobile linezolid resistance genes in enterococci derived from livestock compost at Japanese farms(タイトル和訳中)
  福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本細菌学雑誌, 79, 2, 121, 121, 日本細菌学会, 2024年06月
  英語
• Genomic Analysis of Salmonella Isolated from Canal Water in Bangkok, Thailand(タイトル和訳中)
  Toyting Jirachaya; Nuanmuang Narong; Utrarachkij Fuangfa; Leekitcharoenphon Pimlapas; Aarestrup Frank; 佐藤 豊孝; Thapa Jeewan; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 79, 2, 128, 128, 日本細菌学会, 2024年06月
  英語
• Assessment of antimicrobial resistance laboratory-based surveillance capacity of hospitals in Zambia: findings and implications for system strengthening
  K. Yamba; J. Y. Chizimu; S. Mudenda; C. Lukwesa; R. Chanda; R. Nakazwe; B. Simunyola; M. Shawa; A. C. Kalungia; D. Chanda; T. Mateele; J. Thapa; K. Kapolowe; M. L. Mazaba; M. Mpundu; F. Masaninga; K. Azam; C. Nakajima; Y. Suzuki; N. N. Bakyaita; E. Wesangula; M. Matu; R. Chilengi
  Journal of Hospital Infection, 148, 129, 137, 2024年06月
  研究論文（学術雑誌）
• Carbapenem and colistin-resistant hypervirulent Klebsiella pneumoniae: An emerging threat transcending the egyptian food chain.
  Rana Fahmi Sabala; Akira Fukuda; Chie Nakajima; Yasuhiko Suzuki; Masaru Usui; Mohamed Elhadidy
  Journal of infection and public health, 17, 6, 1037, 1046, 2024年06月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great public health problem and is associated with many disease outbreaks and high mortality rates. Alarmingly, K. pneumoniae has been isolated from food in several recent studies. This study aimed to investigate the prevalence and characteristics of CRKP in food samples from Egypt. METHODS: A total of 311 food samples (including 116 minced meat, 92 chicken meat, 75 diced meat, and 28 mutton) were collected from local markets in Egypt and were screened for CRKP with the determination of their antimicrobial resistance profiles. The whole genome sequence was done for 23 CRKP isolates to clarify the relationship between CRKP from food and human cases in Egypt using the SNP core genome. The conjugation probability of the blaNDM-5 harboring plasmid was identified using oriTfinder RESULTS: CRKP was isolated from 11% (35/311) of the samples, with 45.71% (16/35) of them showing resistance to colistin, one of the last-resort options for treating CRKP-mediated infections. In addition to the carbapenem and colistin resistance, the CRKP isolates frequently exhibited resistance to multiple antimicrobials including β-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and chloramphenicol. In addition, most of the CRKP were potentially hypervirulent K. pneumoniae (HvKP) identified as phylogroup Kp1 and of high-risk groups as detected in STs reported in many human outbreaks globally, such as ST383 and ST147. The core-genome phylogeny showed similarities between the isolates from this study and those previously isolated from clinical human samples in Egypt. In addition, analysis of the plasmid on which blaNDM is encoded revealed that several antimicrobial resistance genes such as blaOXA-9, blaCTX-M-15, aac(6')-Ib, qnrS1, and several virulence genes are encoded on the same plasmid. CONCLUSIONS: This study is significant for food safety and public health and is important to further identify the change in the epidemiology of CRKP infections, especially the consumption of contaminated food products.
• Association of toxin-producing Clostridioides difficile with piglet diarrhea and potential transmission to humans.
  Kouki Takeichi; Akira Fukuda; Chika Shono; Noriyasu Ota; Chie Nakajima; Yasuhiko Suzuki; Masaru Usui
  The Journal of veterinary medical science, 2024年05月27日, ［国内誌］
  英語, 研究論文（学術雑誌）, The pathogenicity of Clostridioides difficile in piglets remains controversial. It is unknown whether C. difficile control helps protect piglet health. To clarify the association between C. difficile presence and piglet diarrhea, isolates were obtained from piglets with and without diarrhea. In addition, to determine the genetic relationship of C. difficile from pigs and humans, we performed whole-genome sequencing (WGS) of C. difficile isolates. Diarrheal and non-diarrheal stool samples were collected from neonatal piglets from five farms in Japan in 2021. To clarify the relationship between C. difficile derived from pigs and those from human clinical cases, WGS of C. difficile isolates was performed. Toxin-positive C. difficile were significantly more prevalent in piglets with diarrhea, although the overall frequency of C. difficile did not differ between piglets with and without diarrhea. This observation indicates an association between toxin-positive C. difficile and diarrhea in piglets. However, further studies are needed to establish a direct causal relationship and to explore other contributing factors to diarrhea in piglets. WGS results showed that C. difficile sequence type (ST)11 including the hypervirulent PCR ribotype 078 isolates derived from Japanese pigs were closely related to ST11 of overseas strains (human clinical and animal-derived) and a Japanese human clinical strain. Toxin-positive C. difficile may cause diarrhea in piglets and hypervirulent C. difficile are spreading among pigs and human populations worldwide.
• Antimicrobial Use Survey and Detection of ESBL-Escherichia coli in Commercial and Medium-/Small-Scale Poultry Farms in Selected Districts of Zambia
  Taona Sinyawa; Misheck Shawa; Geoffrey M. Muuka; Fusya Goma; Paul Fandamu; Joseph Yamweka Chizimu; Cynthia Sipho Khumalo; Malala Mulavu; Masuzyo Ngoma; Herman Moses Chambaro; Harvey Kakoma Kamboyi; Masahiro Kajihara; Hirofumi Sawa; Yasuhiko Suzuki; Hideaki Higashi; Geoffrey Mainda; Musso Munyeme; John Bwalya Muma; Christian Owusu Nyantakyi; Beverly Egyir; Bernard Mudenda Hang’ombe
  Antibiotics, 13, 5, 467, 467, MDPI AG, 2024年05月20日
  研究論文（学術雑誌）, Antimicrobial resistance (AMR) among Escherichia coli from food animals is a rising problem, and heavy antimicrobial use in poultry is a contributing factor. In Zambia, studies linking poultry-associated AMR and antibiotic use (AMU) are rare. This study aimed to investigate commercial and medium-/small-scale poultry farmers’ usage of antimicrobials based on a questionnaire survey in ten districts of Zambia. In addition, the study characterized extended-spectrum β-lactamase (ESBL)-producing E. coli isolates obtained from poultry in the same districts. Data regarding knowledge and usage of antimicrobials were collected from commercial and medium-/small-scale poultry farmers using a pre-tested structured questionnaire. At the same time, cloacal samples were collected and analyzed. One hundred and fifty E. coli isolates were tested for antimicrobial susceptibility using eight antibiotic classes. The isolates were further screened for ESBL production by streaking them on cefotaxime (CTX)-supplemented MacConkey agar, then subjecting them to sequencing on a NextSeq. The questionnaire survey showed that more medium-/small-scale than commercial poultry farmers used antimicrobials (OR = 7.70, 95% CI = 2.88–20.61) but less prescriptions (OR = 0.02, 95% CI = 0.00–0.08). Susceptibility testing revealed that resistance was highest to ampicillin (128/148, 86.5%) and tetracycline (101/136, 74.3%) and that the prevalence of multidrug resistance (MDR) (28/30, 93.3%) was high. Whole-genome sequencing (WGS) of eight (8/30, 26.7%) isolates with CTX Minimum Inhibitory Concentration (MIC) ≥ 4 µg/mL revealed the presence of ESBL-encoding genes blaCTX-M-14, blaCTX-M-55, and blaTEM. WGS also detected other AMR genes for quinolones, aminoglycosides, phenicols, tetracycline, macrolides, and folate-pathway antagonists. Altogether, the questionnaire survey results showed a higher proportion of AMU and lower prescription usage among medium-/small-scale farmers. In addition, our results emphasize the circulation of ESBL-producing E. coli strains with associated MDR. It is critical to educate farmers about AMR risks and to encourage responsible usage of antimicrobials. Furthermore, there is a need to strengthen regulations limiting access to antimicrobials. Finally, there is a need to establish a one health system to guide public health response.
• Genomic analysis of Salmonella isolated from canal water in Bangkok, Thailand.
  Jirachaya Toyting; Narong Nuanmuang; Fuangfa Utrarachkij; Neunghatai Supha; Yuwanda Thongpanich; Pimlapas Leekitcharoenphon; Frank M Aarestrup; Toyotaka Sato; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, 12, 5, e0421623, 2024年05月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, Antimicrobial resistance (AMR) poses an escalating global public health threat. Canals are essential in Thailand, including the capital city, Bangkok, as agricultural and daily water sources. However, the characteristic and antimicrobial-resistance properties of the bacteria in the urban canals have never been elucidated. This study employed whole genome sequencing to characterize 30 genomes of a causal pathogenic bacteria, Salmonella enterica, isolated from Bangkok canal water between 2016 and 2020. The dominant serotype was Salmonella Agona. In total, 35 AMR genes and 30 chromosomal-mediated gene mutations were identified, in which 21 strains carried both acquired genes and mutations associated with fluoroquinolone resistance. Virulence factors associated with invasion, adhesion, and survival during infection were detected in all study strains. 75.9% of the study stains were multidrug-resistant and all the strains harbored the necessary virulence factors associated with salmonellosis. One strain carried 20 resistance genes, including mcr-3.1, mutations in GyrA, ParC, and ParE, and typhoid toxin-associated genes. Fifteen plasmid replicon types were detected, with Col(pHAD28) being the most common type. Comparative analysis of nine S. Agona from Bangkok and 167 from public databases revealed that specific clonal lineages of S. Agona might have been circulating between canal water and food sources in Thailand and globally. These findings provide insight into potential pathogens in the aquatic ecosystem and support the inclusion of environmental samples into comprehensive AMR surveillance initiatives as part of a One Health approach. This approach aids in comprehending the rise and dissemination of AMR and devising sustainable intervention strategies.IMPORTANCEBangkok is the capital city of Thailand and home to a large canal network that serves the city in various ways. The presence of pathogenic and antimicrobial-resistant Salmonella is alarming and poses a significant public health risk. The present study is the first characterization of the genomic of Salmonella strains from Bangkok canal water. Twenty-two of 29 strains (75.9%) were multidrug-resistant Salmonella and all the strains carried essential virulence factors for pathogenesis. Various plasmid types were identified in these strains, potentially facilitating the horizontal transfer of AMR genes. Additional investigations indicated a potential circulation of S. Agona between canal water and food sources in Thailand. The current study underscores the role of environmental water in an urban city as a reservoir of pathogens and these data obtained can serve as a basis for public health risk assessment and help shape intervention strategies to combat AMR challenges in Thailand.
• Effect of WQ-3334 on Campylobacter jejuni carrying a DNA gyrase with dominant amino acid substitutions conferring quinolone resistance.
  Nami Miura-Ajima; Pondpan Suwanthada; Siriporn Kongsoi; Hyun Kim; Ruttana Pachanon; Kentaro Koide; Shigetarou Mori; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2024年04月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Campylobacteriosis stands as one of the most frequent bacterial gastroenteritis worldwide necessitating antibiotic treatment in severe cases and the rise of quinolones-resistant Campylobacter jejuni poses a significant challenge. The predominant mechanism of quinolones-resistance in this bacterium involves point mutations in the gyrA, resulting in amino acid substitution from threonine to isoleucine at 86th position, representing more than 90% of mutant DNA gyrase, and aspartic acid to asparagine at 90th position. WQ-3334, a novel quinolone, has demonstrated strong inhibitory activity against various bacteria. This study aims to investigate the effectiveness of WQ-3334, and its analogues, WQ-4064 and WQ-4065, with a unique modification in R1 against quinolones-resistant C. jejuni. METHODS: The structure-activity relationship of the examined drugs was investigated by measuring IC50 and their antimicrobial activities were accessed by MIC against C. jejuni strains. Additionally, in silico docking simulations were carried out using the crystal structure of the Escherichia coli DNA gyrase. RESULT: WQ-3334 exhibited the lowest IC50 against WT (0.188 ± 0.039 mg/L), T86I (11.0 ± 0.7 mg/L) and D90 N (1.60 ± 0.28 mg/L). Notably, DNA gyrases with T86I substitutions displayed the highest IC50 values among the examined WQ compounds. Moreover, WQ-3334 demonstrated the lowest MICs against wild-type and mutant strains. The docking simulations further confirmed the interactions between WQ-3334 and DNA gyrases. CONCLUSION: WQ-3334 with 6-amino-3,5-difluoropyridine-2-yl at R1 severed as a remarkable candidate for the treatment of foodborne diseases caused by quinolones-resistant C. jejuni as shown by the high inhibitory activity against both wild-type and the predominant quinolones-resistant strains.
• デラフロキサシンのらい菌DNAジャイレースに対する作用(第2報)
  Eomseob Jang; Pondpan Suwanthada; 中島 千絵; 阿戸 学; 向井 徹; 鈴木 定彦
  日本ハンセン病学会雑誌, 93, 1, 21, 21, 日本ハンセン病学会, 2024年04月
  日本語
• Detection of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteriaceae from Diseased Broiler Chickens in Lusaka District, Zambia.
  Chikwanda Chileshe; Misheck Shawa; Nelson Phiri; Joseph Ndebe; Cynthia Sipho Khumalo; Chie Nakajima; Masahiro Kajihara; Hideaki Higashi; Hirofumi Sawa; Yasuhiko Suzuki; Walter Muleya; Bernard Mudenda Hang'ombe
  Antibiotics (Basel, Switzerland), 13, 3, 2024年03月15日, ［国際誌］
  英語, 研究論文（学術雑誌）, Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimisation and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for Gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and Shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all tested antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for blaCTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for blaTEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying blaCTX-M-positive strains were also positive for blaTEM. Sanger sequencing of the PCR products revealed that five (5/6, 83.3%) of the abovementioned isolates possessed the blaCTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health.
• Heated scallop-shell powder and lime nitrogen effectively decrease the abundance of antimicrobial-resistant bacteria in aerobic compost
  Masatoshi Enami; Akira Fukuda; Michi Yamada; Yoshihiro Kobae; Chie Nakajima; Yasuhiko Suzuki; Masaru Usui
  Environmental Technology & Innovation, 103590, 103590, Elsevier BV, 2024年03月, ［査読有り］
  研究論文（学術雑誌）
• Increased expression of CD38 on endothelial cells in SARS-CoV-2 infection in cynomolgus macaque
  Cong Thanh Nguyen; Misako Nakayama; Hirohito Ishigaki; Yoshinori Kitagawa; Akemi Kakino; Marumi Ohno; Masashi Shingai; Yasuhiko Suzuki; Tatsuya Sawamura; Hiroshi Kida; Yasushi Itoh
  Virology, 110052, 110052, Elsevier BV, 2024年03月
  研究論文（学術雑誌）
• Transferable linezolid resistance genes (optrA and poxtA) in enterococci derived from livestock compost at Japanese farms.
  Akira Fukuda; Chie Nakajima; Yasuhiko Suzuki; Masaru Usui
  Journal of global antimicrobial resistance, 2024年02月07日, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Linezolid is a last-resort antimicrobial in human clinical settings to treat multidrug-resistant gram-positive bacterial infections. Mobile linezolid resistance genes (optrA, poxtA, and cfr) have been detected in various sources worldwide. However, the presence of linezolid-not-susceptible bacteria and mobile linezolid resistance genes in Japan remains uncertain. Therefore, we clarified the existence of linezolid-not-susceptible bacteria and mobile linezolid resistance genes in farm environments in Japan. METHODS: Enterococci isolates from feces compost collected from 10 pig and 11 cattle farms in Japan in 2021 were tested for antimicrobial susceptibility and possession of mobile linezolid resistance genes. Whole-genome sequencing of optrA and/or poxtA genes positive-enterococci was performed. RESULTS: Of 103 enterococci isolates, 12 from pig farm compost were not-susceptible (2 resistant and 10 intermediate) to linezolid. These 12 isolates carried mobile linezolid resistance genes on plasmids or chromosomes (5 optrA-positive Enterococcus faecalis, 6 poxtA-positive E. hirae or E. thailandicus, and 1 optrA- and poxtA-positive E. faecium). The genetic structures of optrA- and poxA-carrying plasmids were almost identical to those reported in other countries. These plasmids were capable of transferring among E. faecium and E. faecalis strains. The optrA- and poxtA-positive E. faecium belonged to ST324 (clade A2), a high-risk multidrug-resistant clone. The E. faecalis carrying optrA gene on its chromosome was identified as ST593. CONCLUSIONS: Although linezolid is not used in livestock, linezolid-not-susceptible enterococci could be indirectly selected by frequently used antimicrobials, such as phenicols. Moreover, various enterococci species derived from livestock compost may serve as reservoirs of linezolid resistance genes carried on globally disseminated plasmids and multidrug-resistant high-risk clones.
• Antimicrobial stewardship situation analysis in selected hospitals in Zambia: findings and implications from a national survey.
  Joseph Yamweka Chizimu; Steward Mudenda; Kaunda Yamba; Chileshe Lukwesa; Raphael Chanda; Ruth Nakazwe; Bwalya Simunyola; Misheck Shawa; Aubrey Chichonyi Kalungia; Duncan Chanda; Uchizi Chola; Tebuho Mateele; Jeewan Thapa; Kenneth Kapolowe; Mazyanga Lucy Mazaba; Mirfin Mpundu; Freddie Masaninga; Khalid Azam; Chie Nakajima; Yasuhiko Suzuki; Nathan Nsubuga Bakyaita; Evelyn Wesangula; Martin Matu; Roma Chilengi
  Frontiers in public health, 12, 1367703, 1367703, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Antimicrobial stewardship (AMS) programs are critical in combating antimicrobial resistance (AMR). In Zambia, there is little information regarding the capacity of hospitals to establish and implement AMS programs. The objective of this study was to conduct a baseline assessment of WHO core elements for an AMS program implementation in eight hospitals in Zambia. MATERIALS AND METHODS: We conducted an exploratory cross-sectional study from September 2023 to December 2023 using a self-scoring Periodic National and Healthcare Facility Assessment Tool from the World Health Organization (WHO) policy guidance on integrated AMS activities in human health. Eight public hospitals were surveyed across the five provinces of Zambia. Data was analyzed using the WHO self-scoring tool and thematic analysis. RESULTS: Overall, 62.5% (6/8) of the facilities scored low (below 60%) in implementing AMS programs. Most facilities had challenges with reporting AMS feedback within the hospital (average score = 46%), Drugs and Therapeutics Committee (DTC) functionality (average score = 49%), AMS actions (average score = 50%), education and training (average score = 54%), and leadership commitment to AMS activities (average score = 56%). The overall score for all AMS core elements was average (56%). All the hospitals (100%) did not have an allocated budget for AMS programs. Finally, there were neither antibiograms to guide antimicrobial utilization nor AMS-trained staff in more than 50% of the hospitals surveyed. CONCLUSION: This study found low AMS implementation in these public hospitals, especially where DTCs were non-functional. The identified challenges and gaps require urgent attention for sustainable multidisciplinary AMS programs.
• Phylogenetic diversity and virulence gene characteristics of Escherichia coli from pork and patients with urinary tract infections in Thailand.
  Pramualchai Ketkhao; Fuangfa Utrarachkij; Nattaya Parikumsil; Kritchai Poonchareon; Anusak Kerdsin; Peeraya Ekchariyawat; Pawarut Narongpun; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  PloS one, 19, 7, e0307544, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, Extraintestinal pathogenic Escherichia coli (ExPEC), especially uropathogenic E. coli (UPEC) are responsible for urinary tract infections (UTIs), while diarrheagenic E. coli (DEC) cause foodborne illnesses. These pathogenic E. coli are a serious threat to human health and a public concern worldwide. However, the evidence on pork E. coli (PEC) harboring UPEC virulence-associated genes is currently limited. Therefore, this study aimed to determine the phylogroups, virulence genes, and their association between PEC and UPEC from UTI patients. In this study, 330 E. coli were obtained from archived stock culture isolated from pork (PEC; n = 165) and urine of patients with UTIs (UPEC; n = 165) during 2014-2022. Phylogroups, UPEC- and diarrheagenic E. coli (DEC) associated virulence genes were assessed using PCR assays. The results showed that phylogroups A (50.3%), and B1 (32.1%) were commonly found among PEC whereas phylogroups B2 (41.8%), and C (25.5%) were commonly detected in the UPEC. PEC and UPEC carried similar virulence-associated genes with different percentages. The most frequent UPEC virulence-associated gene among UPEC, and PEC strains was fimH, (93.3%, and 92.1%), followed by iucC (55.2%, and 12.7%), papC (21.8%, and 4.2%), afaC (22.4%, and 0%), hlyCA (17%, and 0.6%), cnf (16.4%, and 0.6%), and sfa/focDE (8.5%, and 4.8%). Additionally, 6 of 27 UPEC virulence-associated gene patterns were found in both PEC and UPEC strains regardless of phylogroups. Furthermore, the DEC virulence-associated genes were found in only 3 strains, one from PEC harboring eae, and two from UPEC carried fimH-bfpA or afaC-CVD432 indicating hybrid strains. Cluster analysis showed a relationship between PEC and UPEC strains and demonstrated that PEC harboring UPEC virulence-associated genes in pork may be associated with UPEC in humans. Food safety and hygiene practices during pork production chain are important procedures for minimizing cross-contamination of these strains that could be transmitted to the consumers.
• Application of Genomic Epidemiology of Pathogens to Farmed Yellowtail Fish Mycobacteriosis in Kyushu, Japan
  Takayuki Wada; Shiomi Yoshida; Takeshi Yamamoto; Lisa Nonaka; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Masayuki Imajoh
  Microbes and Environments, 39, 2, n/a, n/a, Japanese Society of Microbial Ecology, 2024年
  研究論文（学術雑誌）
• Trends, patterns and relationship of antimicrobial use and resistance in bacterial isolates tested between 2015-2020 in a national referral hospital of Zambia.
  Misheck Shawa; Atmika Paudel; Herman Chambaro; Harvey Kamboyi; Ruth Nakazwe; Luke Alutuli; Tuvshinzaya Zorigt; Taona Sinyawa; Mulemba Samutela; Joseph Chizimu; Manyando Simbotwe; Kyoko Hayashida; Naganori Nao; Masahiro Kajihara; Yoshikazu Furuta; Yasuhiko Suzuki; Hirofumi Sawa; Bernard Hang'ombe; Hideaki Higashi
  PloS one, 19, 4, e0302053, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, Increased antimicrobial resistance (AMR) among bacteria underscores the need to strengthen AMR surveillance and promote data-based prescribing. To evaluate trends and associations between antimicrobial usage (AMU) and AMR, we explored a dataset of 34,672 bacterial isolates collected between 2015 and 2020 from clinical samples at the University Teaching Hospital (UTH) in Lusaka, Zambia. The most frequently isolated species were Escherichia coli (4,986/34,672; 14.4%), Staphylococcus aureus (3,941/34,672; 11.4%), and Klebsiella pneumoniae (3,796/34,672; 10.9%). Of the 16 drugs (eight classes) tested, only amikacin and imipenem showed good (> 50%) antimicrobial activity against both E. coli and K. pneumoniae, while nitrofurantoin was effective only in E. coli. Furthermore, 38.8% (1,934/4,980) of E. coli and 52.4% (2,079/3,791) of K. pneumoniae isolates displayed multidrug resistance (MDR) patterns on antimicrobial susceptibility tests. Among S. aureus isolates, 44.6% (973/2,181) were classified as methicillin-resistant (MRSA). Notably, all the MRSA exhibited MDR patterns. The annual hospital AMR rates varied over time, while there was a weak positive relationship (r = 0.38, 95% CI = 0.11-0.60) between the monthly use of third-generation cephalosporins (3GCs) and 3GC resistance among Enterobacterales. Overall, the results revealed high AMR rates that fluctuated over time, with a weak positive relationship between 3GC use and resistance. To our knowledge, this is the first report to evaluate the association between AMU and AMR in Zambia. Our results highlight the need to strengthen antimicrobial stewardship programs and optimize AMU in hospital settings.
• Whole-Genome Investigation of Zoonotic Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 398 Isolated from Pigs and Humans in Thailand.
  Pawarut Narongpun; Pattrarat Chanchaithong; Junya Yamagishi; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 12, 12, 2023年12月16日, ［国際誌］
  英語, 研究論文（学術雑誌）, Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been widespread globally in pigs and humans for decades. Nasal colonization of LA-MRSA is regarded as an occupational hazard to people who are regularly involved in livestock production. Our previous study suggested pig-to-human transmission caused by LA-MRSA clonal complex (CC) 398, using traditional molecular typing methods. Instead, this study aimed to investigate the zoonotic transmission of LA-MRSA CC398 using whole genome sequencing (WGS) technologies. A total of 63 LA-MRSA isolates were identified and characterized in Thailand. Further, the 16 representatives of LA-MRSA CC9 and CC398, including porcine and worker isolates, were subjected to WGS on the Illumina Miseq platform. Core-genome single nucleotide polymorphism (SNP)-based analyses verify the zoonotic transmission caused by LA-MRSA CC398 in two farms. WGS-based characterization suggests the emergence of a novel staphylococcal cassette chromosome (SCC) mec type, consisting of multiple cassette chromosome recombinase (ccr) gene complexes via genetic recombination. Additionally, the WGS analyses revealed putative multi-resistant plasmids and several cross-resistance genes, conferring resistance against drugs of last resort used in humans such as quinupristin/dalfopristin and linezolid. Significantly, LA-MRSA isolates, in this study, harbored multiple virulence genes that may become a serious threat to an immunosuppressive population, particularly for persons who are in close contact with LA-MRSA carriers.
• Insight into the genetic diversity of Mycobacterium bovis isolated from cattle in Malawi.
  Thoko Flav Kapalamula; Joseph Yamweka Chizimu; Mwangala Lonah Akapelwa; David Atomanyi Barnes; Jirachaya Toyting; Precious Bwalya; Linda Basikolo; David Squarre; Herman M Chambaro; Stephen V Gordon; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Research in veterinary science, 164, 105030, 105030, 2023年11月, ［国際誌］
  英語, 研究論文（学術雑誌）, We describe the genetic diversity and phylogenetic relationships of Mycobacterium bovis, isolated from cattle in Malawi. Deletion analysis, spoligotyping, and MIRU-VNTR typing were used to genotype the isolates. Combined with a larger dataset from neighboring countries, the overall M. bovis diversity in Southern Africa was contextualized. From the southern and northern regions of Malawi, 24 isolates were confirmed as M. bovis. We pooled data for the central region (60 isolates) from our recent publication to conceptualize the genetic and phylogenetic relationships of M. bovis in Malawi. European 1 was the dominant M. bovis clonal complex, with 10 unique spoligotype patterns, and SB0131 was ubiquitous. High genetic diversity, a low clustering rate, and many singletons, coupled with a low mutation transmission index, infer a low level of recent transmission, and suggest an endemic status of bovine tuberculosis (bTB) in Malawi. M. bovis isolates from Zambia, Mozambique, and South Africa were genetically related to Malawian isolates, whereas Tanzanian isolates were distantly related. The diversity and phylogenetic analysis suggest earlier introductions and maintenance of M. bovis by constant reinfection from reservoir animals. These findings are fundamental to understanding the source and route of infection in order to establish alternative management strategies for bTB.
• Unprecedented spike flexibility revealed by BSL3 Cryo-ET of active SARS-CoV-2 virions
  Hideo Fukuhara; Hisham M. Dokainish; Shunsuke Kita; Koshiro Tabata; Akira Takasu; Juha T. Huiskonen; Yuki Anraku; Toshiya Senda; David I. Stuart; Michihito Sasaki; Yasuko Orba; Yasuhiko Suzuki; Hirofumi Sawa; Katsumi Maenaka
  2023年10月11日
• Exploration of the novel fluoroquinolones with high inhibitory effect against quinolone-resistant DNA gyrase of Salmonella Typhimurium.
  Jirachaya Toyting; Nami Miura; Fuangfa Utrarachkij; Wimonrat Tanomsridachchai; Lawrence P Belotindos; Pondpan Suwanthada; Thoko Flav Kapalamula; Siriporn Kongsoi; Kentaro Koide; Hyun Kim; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, e0133023, 2023年10月05日, ［国際誌］
  英語, 研究論文（学術雑誌）, Quinolone-resistant nontyphoidal Salmonella, one of the prominent pathogens causing acute gastroenteritis, has become a public health concern globally. The World Health Organization has ranked fluoroquinolone-resistant Salmonella as a high-priority pathogen for researching and developing new antibiotics. WQ-3034 and WQ-3154 are relatively new synthetic fluoroquinolones with distinctive structures. WQ-3034 has 6-amino-3,5-difluoropyridine-2-yl at R1, 3-hydroxyazetidinyl at R7, and the addition of chlorine atom at R8. WQ-3154 has a similar basic pharmacophore to WQ-3034 except for the modification at R8 with a methyl group. In this study, the inhibitory effect and DNA cleavage effect against wild-type (WT) and mutant Salmonella Typhimurium DNA gyrases of WQ-3034 and WQ-3154 were examined along with WQ-3810 and ciprofloxacin by measuring the drug concentration that inhibits half of the enzyme activity (IC50) and the drug concentration that induces 25% of maximum DNA cleavage (CC25). The minimum inhibitory concentration (MIC) of the compounds was assessed against Salmonella Typhimurium and Salmonella Enteritidis. Among four compounds, WQ-3034 demonstrated the highest inhibitory effect against both WT and mutant Salmonella Typhimurium DNA gyrases with amino acid substitution at codon 83 and/or 87, while ciprofloxacin showed the lowest inhibitory effect. Remarkably, WQ-3034 and WQ-3154 exhibited a significantly higher inhibitory effect than ciprofloxacin against Salmonella Typhimurium DNA gyrase with double amino acid substitution, Ser83Phe-Asp87Asn. Similarly, CC25 of WQ-3034 against mutant Salmonella Typhimurium DNA gyrase was lower than ciprofloxacin. Notably, MICs of WQ-3034 and WQ-3154 were higher than ciprofloxacin. In conclusion, this study revealed that WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant nontyphoidal Salmonella. IMPORTANCE Quinolone-resistant nontyphoidal Salmonella is a pressing public health concern, demanding the exploration of novel treatments. In this study, we focused on two innovative synthetic fluoroquinolones, WQ-3034 and WQ-3154. Our findings revealed that these new compounds demonstrate potent inhibitory effects, even against mutant strains that cause resistance to existing quinolones. Hence, WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant Salmonella Typhimurium. Furthermore, the data obtained in this study will be baseline information for antimicrobial drug development.
• The Impact of Substitutions at Positions 1 and 8 of Fluoroquinolones on the Activity Against Mutant DNA Gyrases of Salmonella Typhimurium.
  Pondpan Suwanthada; Siriporn Kongsoi; Nami Miura; Lawrence P Belotindos; Chayada Piantham; Jirachaya Toyting; Mwangala L Akapelwa; Ruttana Pachanon; Kentaro Koide; Hyun Kim; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Microbial drug resistance (Larchmont, N.Y.), 2023年10月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, Although many drug-resistant nontyphoidal Salmonella (NTS) infections are reported globally, their treatment is challenging owing to the ineffectiveness of the currently available antimicrobial drugs against resistant bacteria. It is therefore essential to discover novel antimicrobial drugs for the management of these infections. In this study, we report high inhibitory activities of the novel fluoroquinolones (FQs; WQ-3810 and WQ-3334) with substitutions at positions R-1 by 6-amino-3,5-difluoropyridine-2-yl and R-8 by methyl group or bromine, respectively, against wild-type and mutant DNA gyrases of Salmonella Typhimurium. The inhibitory activities of these FQs were assessed against seven amino acid substitutions in DNA gyrases conferring FQ resistance to S. Typhimurium, including high-level resistant mutants, Ser83Ile and Ser83Phe-Asp87Asn by in vitro DNA supercoiling assay. Drug concentrations of WQ compounds with 6-amino-3,5-difluoropyridine-2-yl that suppressed DNA supercoiling by 50% (IC50) were found to be ∼150-fold lower than ciprofloxacin against DNA gyrase with double amino acid substitutions. Our findings highlight the importance of the chemical structure of an FQ drug on its antimicrobial activity. Particularly, the presence of 6-amino-3,5-difluoropyridine-2-yl at R-1 and either methyl group or bromine at R-8 of WQ-3810 and WQ-3334, respectively, was associated with improved antimicrobial activity. Therefore, WQ-3810 and WQ-3334 are promising candidates for use in the treatment of patients infected by FQ-resistant Salmonella spp.
• Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours.
  Naoya Maekawa; Satoru Konnai; Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Yumiko Kagawa; Satoshi Takagi; Hiroshi Ohta; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
  PloS one, 18, 10, e0291727, 2023年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, Immune checkpoint inhibitors (ICIs) have been developed for canine tumour treatment, and pilot clinical studies have demonstrated their antitumour efficacy in dogs with oral malignant melanoma (OMM). Although ICIs have been approved for various human malignancies, their clinical benefits in other tumour types remain to be elucidated in dogs. Here, we conducted a clinical study of c4G12, a canine chimeric anti-PD-L1 antibody, to assess its safety and efficacy in dogs with various advanced malignant tumours (n = 12) at the Veterinary Teaching Hospital of Hokkaido University from 2018 to 2023. Dogs with digit or foot pad malignant melanoma (n = 4), osteosarcoma (n = 2), hemangiosarcoma (n = 1), transitional cell carcinoma (n = 1), nasal adenocarcinoma (n = 1), B-cell lymphoma (n = 1), or undifferentiated sarcoma (n = 2) were treated with 2 or 5 mg/kg c4G12 every 2 weeks. Treatment-related adverse events of any grade were observed in eight dogs (66.7%), including elevated aspartate aminotransferase (grade 3) in one dog (8.3%) and thrombocytopenia (grade 4) in another dog (8.3%). Among dogs with target disease at baseline (n = 8), as defined by the response evaluation criteria for solid tumours in dogs (cRECIST), one dog with nasal adenocarcinoma and another with osteosarcoma experienced a partial response (PR), with an objective response rate of 25.0% (2 PR out of 8 dogs; 95% confidence interval: 3.2-65.1%). These results suggest that c4G12 is safe and tolerable and shows antitumor effects in dogs with malignant tumours other than OMM. Further clinical studies are warranted to identify the tumour types that are most likely to benefit from c4G12 treatment.
• Development of a piezo biosensor for pathogen-specific biopolymer detection using a self-assembly barium titanate/polyvinylidene fluoride composite material
  Mariko Takeda; Hayato Yoshino; Haruna Yamazaki; Takamichi Hirata; Takashi Kuroiwa; Chie Nakajima; Yasuhiko Suzuki; Fumio Munakata
  Sensors and Actuators A: Physical, 360, 114545, 114545, Elsevier BV, 2023年10月
  研究論文（学術雑誌）
• Development of a high-affinity anti-bovine PD-1 rabbit-bovine chimeric antibody using an efficient selection and large production system.
  Tomohiro Okagawa; Satoru Konnai; Shinya Goto; Yamato Sajiki; Otgontuya Ganbaatar; Kei Watari; Hayato Nakamura; Cai-Xia Wang; Taro Tachibana; Yukinari Kato; Yayoi Kameda; Junko Kohara; Nobuhiro Terasaki; Manabu Kubota; Akira Takeda; Hirofumi Takahashi; Yasuhiko Suzuki; Naoya Maekawa; Shiro Murata; Kazuhiko Ohashi
  Veterinary research, 54, 1, 82, 82, 2023年09月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, Immune checkpoint molecules PD-1/PD-L1 cause T-cell exhaustion and contribute to disease progression in chronic infections of cattle. We established monoclonal antibodies (mAbs) that specifically inhibit the binding of bovine PD-1/PD-L1; however, conventional anti-PD-1 mAbs are not suitable as therapeutic agents because of their low binding affinity to antigen. In addition, their sensitivity for the detection of bovine PD-1 is low and their use for immunostaining PD-1 is limited. To address these issues, we established two anti-bovine PD-1 rabbit mAbs (1F10F1 and 4F5F2) and its chimeric form using bovine IgG1 (Boch1D10F1), which exhibit high binding affinity. One of the rabbit mAb 1D10F1 binds more strongly to bovine PD-1 compared with a conventional anti-PD-1 mAb (5D2) and exhibits marked inhibitory activity on the PD-1/PD-L1 interaction. In addition, PD-1 expression in bovine T cells could be detected with higher sensitivity by flow cytometry using 1D10F1. Furthermore, we established higher-producing cells of Boch1D10F1 and succeeded in the mass production of Boch1D10F1. Boch1D10F1 exhibited a similar binding affinity to bovine PD-1 and the inhibitory activity on PD-1/PD-L1 binding compared with 1D10F1. The immune activation by Boch1D10F1 was also confirmed by the enhancement of IFN-γ production. Finally, Boch1D10F1 was administered to bovine leukemia virus-infected cows to determine its antiviral effect. In conclusion, the high-affinity anti-PD-1 antibody developed in this study represents a powerful tool for detecting and inhibiting bovine PD-1 and is a candidate for PD-1-targeted immunotherapy in cattle.
• Retrospective identification of pathogenic mycobacterial species in fish: Mycobacterium pseudoshottsii YM-3, isolated from a yellowtail fish in 1986 in Kochi, Japan
  Masayuki Imajoh; Shiomi Yoshida; Lisa Nonaka; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Takayuki Wada
  Microbiology Resource Announcements, American Society for Microbiology, 2023年09月15日
  研究論文（学術雑誌）, ABSTRACT
  
  The complete genome sequence of mycobacterial strain YM-3, isolated from cultured yellowtail in 1986, was determined. The strain was Mycobacterium pseudoshottsii , a closely related subspecies of Mycobacterium marinum , so the strain was isolated earlier than the first report of the subspecies in 2005.
• Ending tuberculosis by 2030: understanding the transmission.
  Basu Dev Pandey; Mya Myat Ngwe Tun; Yogendra Shah; Yasuhiko Suzuki; Kouichi Morita
  The Lancet regional health. Western Pacific, 38, 100851, 100851, 2023年09月, ［国際誌］
  英語, 研究論文（学術雑誌）
• Molecular Characterisation of Mycobacterium bovis Isolates from Cattle Slaughtered in Adamawa and Gombe States, North-Eastern Nigeria
  Sadiq Mohammed Damina; David Atomanyi Barnes; Bitrus Inuwa; Gulak Hussaini Ularamu; Mohammed Bello; Olu Solomon Okaiyeto; Ayuba Caleb Kudi; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Current Issues in Molecular Biology, 45, 7, 6055, 6066, MDPI AG, 2023年07月19日
  研究論文（学術雑誌）, Bovine tuberculosis is endemic in Nigeria with control measures as provided by the laws of the country being minimally enforced mostly at the abattoirs only. This study focused on bovine tuberculosis in Adamawa and Gombe States. Tuberculosis lesions were observed in 183 of 13,688 slaughtered cattle in the regions between June and December 2020. Analysis of tissue samples resulted in 17 Mycobacterium bovis isolates, predominantly from Gombe State. Spoligotyping identified four spoligotypes, including SB0944, SB1025, SB1104, and one novel pattern. MIRU-VNTR analysis further differentiated these spoligotypes into eight profiles. All isolates belonged to the Af1 clonal complex. The study emphasises the need for broader coverage and more isolates to comprehensively understand the molecular epidemiology of bovine tuberculosis in Nigeria. To enhance research and surveillance, a cost-effective approach is proposed, utilising a discriminatory VNTR panel comprising five or nine loci. The five-locus panel consists of ETR-C, QUB26, QUB11b, MIRU04, and QUB323. Alternatively, the nine-locus panel includes ETR-A, ETR-B, QUB11a, and MIRU26. Implementing this approach would provide valuable insights into the genetic diversity of M. bovis strains in Nigeria. These findings are crucial for developing effective control measures and minimising the impact of bovine tuberculosis on both animal and human health.
• High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens.
  Shota Fukuzawa; Toyotaka Sato; Kotaro Aoki; Soh Yamamoto; Noriko Ogasawara; Chie Nakajima; Yasuhiko Suzuki; Motohiro Horiuchi; Satoshi Takahashi; Shin-Ichi Yokota
  Annals of clinical microbiology and antimicrobials, 22, 1, 60, 60, 2023年07月15日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed. METHODS: Clinical isolates identified as "E. cloacae complex" by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR. RESULTS: Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-L-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates. CONCLUSIONS: Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.
• Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia
  Joseph Yamweka Chizimu; Eddie Samuneti Solo; Precious Bwalya; Thoko Flav Kapalamula; Kaemba Kunkuta Mwale; David Squarre; Misheck Shawa; Patrick Lungu; David Atomanyi Barnes; Kaunda Yamba; Tiza Mufune; Herman Chambaro; Harvey Kamboyi; Musso Munyeme; Bernard Mudenda Hang’ombe; Nathan Kapata; Victor Mukonka; Roma Chilengi; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics, 12, 7, 1126, 1126, MDPI AG, 2023年06月29日
  研究論文（学術雑誌）, The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes.
• Colistin-resistant bacteria poses few risks under physiological conditions
  Soh Yamamoto; Masaru Usui; Noriko Ogasawara; Wataru Hayashi; Masato Suzuki; Noriyuki Nagano; Chie Nakajima; Yasuhiko Suzuki; Motohiro Horiuchi; Satoshi Takahashi; Shin-ichi Yokota; Yutaka Tamura; Toyotaka Sato
  Research Square, Research Square Platform LLC, 2023年06月21日
  研究論文（学術雑誌）, Abstract
  
  Globally, 5.0 million people die annually from infections associated with antimicrobial-resistant bacteria, most commonly Escherichia coli¹. As colistin is a last-resort antibiotic for multidrug-resistant bacterial infections, the global spread of plasmid-mediated colistin resistance genes (mcr) gene is considered a major public health risk^2-4. However, the actual health risks of colistin resistance in hazardous bacteria have never been evaluated under physiological conditions. Here, we show that the fitness/virulence and colistin resistance of the pandemic multidrug-resistant E. coli clone ST131⁵ very depending on the acquired colistin resistance determinants and differ between physiological and in vitro conditions. The fitness/virulence of ST131 was unaffected by chromosomal-gene (pmrB) mutations or the acquisition of mcr-5-harbouring plasmids in mouse models. However, the acquisition of mcr-1- or mcr-3-harbouring plasmids attenuated fitness/virulence and promoted colistin susceptibility in human serum. We identified two virulence attenuation factors (vafA and vafB) on the pIncI2_mcr-1 plasmid that hijacked the ST131 transcriptome and inhibited nucleotide synthesis, attenuating colistin resistance. Our results demonstrate that colistin resistance poses much less of a threat than believed^6,7. We suggest that “nonresistance genes,” rather than resistance genes, are important antimicrobial resistance determinants for human health because they determine fitness/virulence and ultimately antimicrobial susceptibility under physiological conditions.
• Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma.
  Tatsuya Deguchi; Naoya Maekawa; Satoru Konnai; Ryo Owaki; Kenji Hosoya; Keitaro Morishita; Motoji Nakamura; Tomohiro Okagawa; Hiroto Takeuchi; Sangho Kim; Ryohei Kinoshita; Yurika Tachibana; Madoka Yokokawa; Satoshi Takagi; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Cancers, 15, 11, 2023年06月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity in patients with cancer. This study retrospectively examined the therapeutic efficacy of combination therapy (hypofractionated RT and anti-PD-L1 antibody [c4G12]) in dogs with pulmonary metastatic oral malignant melanoma. The intrathoracic clinical benefit rate (CBR)/median overall survival (OS) in the no RT (n = 20, free from the effect of RT), previous RT (n = 9, received RT ≤8 weeks prior to the first c4G12 dose), and concurrent RT (n = 10, c4G12 therapy within ±1 week of the first RT fraction) groups were 10%/185 days, 55.6%/283.5 days (p < 0.05 vs. no RT group), and 20%/129 days (p > 0.05 vs. no RT group), respectively. The adverse events were considered to be tolerable in the combination therapy. Thus, hypofractionated RT before the initiation of c4G12 therapy can be an effective approach for enhancing the therapeutic efficacy of immunotherapy, with acceptable safety profiles. Further prospective clinical studies are required to confirm the findings of this study.
• Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in sheep.
  Wisa Tiyamanee; Satoru Konnai; Tomohiro Okagawa; Yutaro Nojima; Otgontuya Ganbaatar; Naoya Maekawa; Rie Hasebe; Yumiko Kagawa; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Veterinary immunology and immunopathology, 261, 110609, 110609, 2023年05月11日, ［国際誌］
  英語, 研究論文（学術雑誌）, Sheep have been used as a large animal experimental model for studying infectious diseases. However, due to a lack of staining antibodies and reagents, immunological studies on sheep have not progressed. The immunoinhibitory receptor programmed death-1 (PD-1) is expressed on T lymphocytes. The interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. We previously reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections using anti-bovine PD-L1 monoclonal antibodies (mAbs). Furthermore, we found that blocking antibodies against PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy of cattle. However, the immunological role of the PD-1/PD-L1 pathway in chronic diseases of sheep remains unknown. In this study, we identified cDNA sequences of ovine PD-1 and PD-L1 and examined the cross-activity of anti-bovine PD-L1 mAbs against ovine PD-L1 as well as the expression of PD-L1 in ovine listeriosis. The amino acid sequences of ovine PD-1 and PD-L1 share a high degree of identity and similarity with homologs from ruminants and other mammalian species. Anti-bovine PD-L1 mAb recognized ovine PD-L1 on lymphocytes in the flow cytometric assay. Furthermore, an immunohistochemical staining confirmed the PD-L1 expression on macrophages in the brain lesions of ovine listeriosis. These findings indicated that our anti-PD-L1 mAb would be useful for analyzing the ovine PD-1/PD-L1 pathway. Further research is needed to determine the immunological role of PD-1/PD-L1 in chronic diseases such as BLV infection through experimental infection of sheep.
• Characterization of DNA Gyrase Activity and Elucidation of the Impact of Amino Acid Substitution in GyrA on Fluoroquinolone Resistance in Mycobacterium avium.
  Jeewan Thapa; Joseph Yamweka Chizimu; Soyoka Kitamura; Mwangala Lonah Akapelwa; Pondpan Suwanthada; Nami Miura; Jirachaya Toyting; Tomoyasu Nishimura; Naoki Hasegawa; Yukiko Nishiuchi; Stephen V Gordon; Chie Nakajima; Yasuhiko Suzuki
  Microbiology spectrum, e0508822, 2023年04月17日, ［国際誌］
  英語, 研究論文（学術雑誌）, Mycobacterium avium, a member of the M. avium complex (MAC), is the major pathogen contributing to nontuberculous mycobacteria (NTM) infections worldwide. Fluoroquinolones (FQs) are recommended for the treatment of macrolide-resistant MACs. The association of FQ resistance and mutations in the quinolone resistance-determining region (QRDR) of gyrA of M. avium is not yet clearly understood, as many FQ-resistant clinical M. avium isolates do not have such mutations. This study aimed to elucidate the role of amino acid substitution in the QRDR of M. avium GyrA in the development of FQ resistance. We found four clinical M. avium subsp. hominissuis isolates with Asp-to-Gly change at position 95 (Asp95Gly) and Asp95Tyr mutations in gyrA that were highly resistant to FQs and had 2- to 32-fold-higher MICs than the wild-type (WT) isolates. To clarify the contribution of amino acid substitutions to FQ resistance, we produced recombinant WT GyrA, GyrB, and four GyrA mutant proteins (Ala91Val, Asp95Ala, Asp95Gly, and Asp95Tyr) to elucidate their potential role in FQ resistance, using them to perform FQ-inhibited DNA supercoiling assays. While all the mutant GyrAs contributed to the higher (1.3- to 35.6-fold) FQ 50% inhibitory concentration (IC50) than the WT, Asp95Tyr was the most resistant mutant, with an IC50 15- to 35.6-higher than that of the WT, followed by the Asp95Gly mutant, with an IC50 12.5- to 17.6-fold higher than that of the WT, indicating that these amino acid substitutions significantly reduced the inhibitory activity of FQs. Our results showed that amino acid substitutions in the gyrA of M. avium contribute to FQ resistance. IMPORTANCE The emergence of fluoroquinolone (FQ) resistance has further compounded the control of emerging Mycobacterium avium-associated nontuberculous mycobacteria infections worldwide. For M. avium, the association of FQ resistance and mutations in the quinolone resistance-determining region (QRDR) of gyrA is not yet clearly understood. Here, we report that four clinical M. avium isolates with a mutation in the QRDR of gyrA were highly resistant to FQs. We further clarified the impact of mutations in the QRDR of GyrA proteins by performing in vitro FQ-inhibited DNA supercoiling assays. These results confirmed that, like in Mycobacterium tuberculosis, mutations in the QRDR of gyrA also strongly contribute to FQ resistance in M. avium. Since many FQ-resistant M. avium isolates do have these mutations, the detailed molecular mechanism of FQ resistance in M. avium needs further exploration.
• Direct detection of Mycobacterium bovis by a dry loop-mediated isothermal amplification assay in cattle samples collected during routine abattoir examination in Malawi.
  Thoko Flav Kapalamula; Jeewan Thapa; Kyoko Hayashida; Joseph Chizimu; Wimonrat Tanomsridachchai; Mirriam Ethel Nyenje; Rajab Mkakosya; Chie Nakajima; Yasuhiko Suzuki
  Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc, 10406387231164596, 10406387231164596, 2023年04月08日, ［国際誌］
  英語, 研究論文（学術雑誌）, The lack of quick, accurate, and low-cost detection methods has hindered the active control strategies for bovine tuberculosis (bTB) in resource-limited countries with a high burden of disease. We developed a dry loop-mediated isothermal amplification (LAMP) assay for rapid and specific detection of Mycobacterium bovis, the principal causative agent of bTB, and evaluated the efficacy of the assay using suspected bTB samples collected during routine meat inspection at major regional abattoirs in Malawi. Template genomic DNA was extracted directly from the granulomatous bTB-like lesion (crude extracted DNA), as well as growth from the incubated mycobacterial growth indicator tubes (MGIT). Field results were visualized by the naked eye within 40 min following a color change of the amplified products. The sensitivity and specificity of the dry LAMP assay while using 152 DNA samples extracted from MGIT with confirmed M. bovis results were 98% and 88%, respectively. When 43 randomly selected crude DNA samples from lesions were used, the sensitivity and specificity of the dry LAMP assay were 100% and 75%, respectively. Our LAMP assay offers the potential to meet the demands for a low-cost and rapid field detection tool for bTB in resource-limited countries in which bTB is endemic.
• デラフロキサシンのらい菌DNAジャイレースに対する作用
  鈴木 定彦; 朴 鐘勲; Pondpan Suwanthada; 中島 千絵
  日本ハンセン病学会雑誌, 92, 1, 23, 23, 日本ハンセン病学会, 2023年04月
  日本語
• Determination of the Prevalence and Antimicrobial Resistance of Enterococcus faecalis and Enterococcus faecium Associated with Poultry in Four Districts in Zambia.
  Grace Mwikuma; Henson Kainga; Simegnew Adugna Kallu; Chie Nakajima; Yasuhiko Suzuki; Bernard Mudenda Hang'ombe
  Antibiotics (Basel, Switzerland), 12, 4, 2023年03月28日, ［国際誌］
  英語, 研究論文（学術雑誌）, The presence of antimicrobial-resistant Enterococci in poultry is a growing public health concern worldwide due to its potential for transmission to humans. The aim of this study was to determine the prevalence and patterns of antimicrobial resistance and to detect drug-resistant genes in Enterococcus faecalis and E. faecium in poultry from four districts in Zambia. Identification of Enterococci was conducted using phenotypic methods. Antimicrobial resistance was determined using the disc diffusion method and antimicrobial resistance genes were detected using polymerase chain reaction and gene-specific primers. The overall prevalence of Enterococci was 31.1% (153/492, 95% CI: 27.1-35.4). Enterococcus faecalis had a significantly higher prevalence at 37.9% (58/153, 95% CI: 30.3-46.1) compared with E. faecium, which had a prevalence of 10.5% (16/153, 95% CI: 6.3-16.7). Most of the E. faecalis and E. faecium isolates were resistant to tetracycline (66/74, 89.2%) and ampicillin and erythromycin (51/74, 68.9%). The majority of isolates were susceptible to vancomycin (72/74, 97.3%). The results show that poultry are a potential source of multidrug-resistant E. faecalis and E. faecium strains, which can be transmitted to humans. Resistance genes in the Enterococcus species can also be transmitted to pathogenic bacteria if they colonize the same poultry, thus threatening the safety of poultry production, leading to significant public health concerns.
• Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.
  Shinsuke Muraoka; Takuya Oguri; Risa Kimura; Keita Sakurai; Yasuhiko Suzuki; Hiroyuki Shimizu; Satoshi Shinoda; Naoki Koketsu; Yoshio Araki; Ryuta Saito
  Acta neurochirurgica, 165, 3, 647, 650, 2023年03月, ［国際誌］
  英語, 研究論文（学術雑誌）, Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.
• Corrigendum to 'Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan' [Journal of Global Antimicrobial Resistance 27 (2021) 150-155].
  Yukari Fukushima; Toyotaka Sato; Naoyuki Tsukamoto; Chie Nakajima; Yasuhiko Suzuki; Satoshi Takahashi; Shin-Ichi Yokota
  Journal of global antimicrobial resistance, 32, 195, 195, 2023年03月, ［国際誌］
  英語
• Enhancement of Vaccine-Induced T-Cell Responses by PD-L1 Blockade in Calves.
  Tomohiro Okagawa; Satoru Konnai; Hayato Nakamura; Otgontuya Ganbaatar; Yamato Sajiki; Kei Watari; Haruka Noda; Mitsuru Honma; Yukinari Kato; Yasuhiko Suzuki; Naoya Maekawa; Shiro Murata; Kazuhiko Ohashi
  Vaccines, 11, 3, 2023年03月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Interactions between programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) cause functional exhaustion of T cells by inducing inhibitory signals, thereby attenuating effector functions of T cells. We have developed an anti-bovine PD-L1 blocking antibody (Ab) and have demonstrated that blockade of the interaction between PD-1 and PD-L1 reactivates T-cell responses in cattle. In the present study, we examined the potential utility of PD-1/PD-L1-targeted immunotherapy in enhancing T-cell responses to vaccination. Calves were inoculated with a hexavalent live-attenuated viral vaccine against bovine respiratory infections in combination with treatment with an anti-PD-L1 Ab. The expression kinetics of PD-1 in T cells and T-cell responses to viral antigens were measured before and after vaccination to evaluate the adjuvant effect of anti-PD-L1 Ab. PD-1 expression was upregulated in vaccinated calves after the administration of a booster vaccination. The activation status of CD4+, CD8+, and γδTCR+ T cells was enhanced by the combination of vaccination and PD-L1 blockade. In addition, IFN-γ responses to viral antigens were increased following combinatorial vaccination with PD-L1 blockade. In conclusion, the blockade of the PD-1/PD-L1 interaction enhances T-cell responses induced by vaccination in cattle, indicating the potential utility of anti-PD-L1 Ab in improving the efficacy of current vaccination programs.
• タイの運河由来Salmonella属におけるプラスミドを介したキノロン系薬耐性遺伝子の有病率(Prevalence of plasmid-mediated quinolone resistance genes in Salmonella spp. from canals of Thailand)
  Toyting Jirachaya; Utrarachkij Fuangfa; Supha Neunghatai; Thongpanich Yuwanda; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 78, 1, 70, 70, 日本細菌学会, 2023年02月
  英語
• SalmonellaTyphimuriumのフルオロキノロン耐性に及ぼすGyrAおよびQnrB19のアミノ酸置換の影響(Impact of mutations in GyrA and QnrB19 on resistance to fluoroquinolone in Salmonella Typhimurium)
  Suwanthada Pondpan; Thapa Jeewan; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 78, 1, 105, 105, 日本細菌学会, 2023年02月
  英語
• Mycobacterium avium gyrAにおけるフルオロキノロン耐性関連変異が耐性へ果たす役割(Role of fluoroquinolone resistance-associated mutations in Mycobacterium avium gyrA to resistance)
  Thapa Jeewan; Chizimu Joseph Yamweka; 北村 そよか; Akapelwa Mwangala Lonah; Suwanthada Pondpan; 三浦 菜実; Toyting Jirachaya; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 78, 1, 105, 105, 日本細菌学会, 2023年02月
  英語
• タイにおける豚からヒトへのLA-MRSAの人獣共通感染の全ゲノム解析(Whole Genome Analysis of Zoonotic Transmission of LA-MRSA from Pigs to Humans in Thailand)
  Narongpun Pawarut; チャンチャイトン・パッタラット; 山岸 潤也; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 78, 1, 109, 109, 日本細菌学会, 2023年02月
  英語
• 日本で分離されたM.avium臨床分離株におけるLevofloxacinのMICに対するmfpAをエンコードするPRPの影響(The effect of mfpA encoding PRP on the MICs of Levofloxacin in M.avium clinical isolates from Japan)
  Akapelwa Mwangala; 会津 勇樹[大内]; Chizimu Joseph Yamweka; Kapalamula Thoko Flav; Menda Conscilliah Rhombohl; 西内 由紀子; 鈴木 定彦; 中島 千絵
  日本細菌学雑誌, 78, 1, 151, 151, 日本細菌学会, 2023年02月
  英語
• Prevalence and risk factors of bovine tuberculosis in slaughtered cattle, Malawi.
  Thoko Flav Kapalamula; Francis Kawonga; Misheck Shawa; Joseph Chizimu; Jeewan Thapa; Mirriam Ethel Nyenje; Rajhab Sawasawa Mkakosya; Kyoko Hayashida; Stephen Gordon; Chie Nakajima; Musso Munyeme; Bernard M Hang'ombe; Yasuhiko Suzuki
  Heliyon, 9, 2, e13647, 2023年02月, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine tuberculosis (bTB) is an infectious disease with significant socioeconomic, animal, and public health impacts. However, the prevalence of bTB remains largely unclear in Malawi due to a paucity of information. Additionally, the existence of multiple risk factors is postulated to enhance bTB transmission in animals. A cross-sectional survey to estimate the prevalence of bTB, animal characteristics and identify associated risk factors was conducted from slaughtered cattle at three major regional abattoirs (southern, central and northern regions) in Malawi. Out of a total of 1547 cattle examined, 154 (9.95%) had bTB-like lesions in various visceral organs and lymph nodes; one sample per animal was collected, processed, and cultured in the in the BACTEC Mycobacterial growth indicator tube (MGIT) 960 system. From the 154 cattle that showed tuberculous like lesions, only 112 were positive on MGIT and 87 were confirmed to have M. bovis based on multiplex PCR. Cattle from the southern region (odds ratio (OR) = 1.96, 95% CI: 1.03-3.85) and central region (OR = 2.00, 95% CI: 1.16-3.56) were more likely presented with bTB-like lesions at slaughter than from the northern region. The risk of having bTB-like lesions was higher in females (OR = 1.51, CI: 1.00-2.29), older cattle (OR = 2.17, CI: 1.34-3.37), and crossbreeds (OR = 1.67, 95% CI: 1.12-2.47) than in males, younger animals, and Malawi Zebu breed, respectively. The high prevalence of bTB is of critical concern and necessitates active surveillance and strengthening of the current control strategies under a One Health (OH) approach at the animal-human interface.
• Combined Immune Checkpoint Blockade Enhances Antiviral Immunity against Bovine Leukemia Virus.
  Hayato Nakamura; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Yamato Sajiki; Kei Watari; Kana Kamitani; Maya Saito; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Journal of virology, 97, 1, e0143022, 2023年01月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leukosis (EBL) in cattle and is widespread in many countries, including Japan. Recent studies have revealed that the expression of immunoinhibitory molecules, such as programmed death-1 (PD-1) and PD-ligand 1, plays a critical role in immunosuppression and disease progression during BLV infection. In addition, a preliminary study has suggested that another immunoinhibitory molecule, T-cell immunoglobulin domain and mucin domain-3 (TIM-3), is involved in immunosuppression during BLV infection. Therefore, this study was designed to further elucidate the immunoinhibitory role of immune checkpoint molecules in BLV infection. TIM-3 expression was upregulated on peripheral CD4+ and CD8+ T cells in BLV-infected cattle. Interestingly, in EBL cattle, CD4+ and CD8+ T cells infiltrating lymphomas expressed TIM-3. TIM-3 and PD-1 were upregulated and coexpressed in peripheral CD4+ and CD8+ T cells from BLV-infected cattle. Blockade by anti-bovine TIM-3 monoclonal antibody increased CD69 expression on T cells and gamma interferon (IFN-γ) production from peripheral blood mononuclear cells from BLV-infected cattle. A syncytium formation assay also demonstrated the antiviral effects of TIM-3 blockade against BLV infection. The combined inhibition of TIM-3 and PD-1 pathways significantly enhanced IFN-γ production and antiviral efficacy compared to inhibition alone. In conclusion, the combined blockade of TIM-3 and PD-1 pathways shows strong immune activation and antiviral effects and has potential as a novel therapeutic method for BLV infection. IMPORTANCE Enzootic bovine leukosis caused by bovine leukemia virus (BLV) is an important viral disease in cattle, causing severe economic losses to the cattle industry worldwide. The molecular mechanisms of BLV-host interactions are complex. Previously, it was found that immune checkpoint molecules, such as PD-1, suppress BLV-specific Th1 responses as the disease progresses. To date, most studies have focused only on how PD-1 facilitates escape from host immunity in BLV-infected cattle and the antiviral effects of the PD-1 blockade. In contrast, how T-cell immunoglobulin domain and mucin domain-3 (TIM-3), another immune checkpoint molecule, regulates anti-BLV immune responses is rarely reported. It is also unclear why PD-1 inhibition alone was insufficient to exert anti-BLV effects in previous clinical studies. In this study, the expression profile of TIM-3 in T cells derived from BLV-infected cattle suggested that TIM-3 upregulation is a cause of immunosuppression in infected cattle. Based on these results, anti-TIM-3 antibody was used to experimentally evaluate its function in influencing immunity against BLV. Results indicated that TIM-3 upregulation induced by BLV infection suppressed T-cell activation and antiviral cytokine production. Some T cells coexpressed PD-1 and TIM-3, indicating that simultaneous inhibition of PD-1 and TIM-3 with their respective antibodies synergistically restored antiviral immunity. This study could open new avenues for treating bovine chronic infections.
• Sensitive detection of Mycobacterium bovis in spiked milk using a polymerase chain reaction assay
  Marvin A. Villanueva; Yasuhiko Suzuki; Chie Nakajima; Haruka Suzuki; Yukari Fukushima; Claro N. Mingala
  Archives of Veterinary Science, 28, 4, 1, 6, 2023年
  研究論文（学術雑誌）
• Field-deployable multiplex detection method of SARS-CoV-2 and influenza virus using loop-mediated isothermal amplification and DNA chromatography.
  Kyoko Hayashida; Alejandro Garcia; Lavel Chinyama Moonga; Tatsuki Sugi; Kodera Takuya; Mitsuo Kawase; Fumihiro Kodama; Atsushi Nagasaka; Nobuhisa Ishiguro; Ayato Takada; Masahiro Kajihara; Naganori Nao; Masashi Shingai; Hiroshi Kida; Yasuhiko Suzuki; William W Hall; Hirofumi Sawa; Junya Yamagishi
  PloS one, 18, 5, e0285861, 2023年, ［国際誌］
  英語, 研究論文（学術雑誌）, A novel multiplex loop-mediated isothermal amplification (LAMP) method combined with DNA chromatography was developed for the simultaneous detection of three important respiratory disease-causing viruses: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus. Amplification was performed at a constant temperature, and a positive result was confirmed by a visible colored band. An in-house drying protocol with trehalose was used to prepare the dried format multiplex LAMP test. Using this dried multiplex LAMP test, the analytical sensitivity was determined to be 100 copies for each viral target and 100-1000 copies for the simultaneous detection of mixed targets. The multiplex LAMP system was validated using clinical COVID-19 specimens and compared with the real-time qRT-PCR method as a reference test. The determined sensitivity of the multiplex LAMP system for SARS-CoV-2 was 71% (95% CI: 0.62-0.79) for cycle threshold (Ct) ≤ 35 samples and 61% (95% CI: 0.53-0.69) for Ct ≤40 samples. The specificity was 99% (95%CI: 0.92-1.00) for Ct ≤35 samples and 100% (95%CI: 0.92-1.00) for the Ct ≤40 samples. The developed simple, rapid, low-cost, and laboratory-free multiplex LAMP system for the two major important respiratory viral diseases, COVID-19 and influenza, is a promising field-deployable diagnosis tool for the possible future 'twindemic, ' especially in resource-limited settings.
• In vitro evaluation of Lactiplantibacillus plantarum HOKKAIDO strain, effective lactic acid bacteria for calf diarrhea.
  Mari Ikehata; Satoru Konnai; Tomohiro Okagawa; Kentaro Abe; Mitsuru Honma; Toru Kitamura; Naoya Maekawa; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Frontiers in veterinary science, 10, 1145445, 1145445, 2023年, ［国際誌］
  英語, 研究論文（学術雑誌）, Calf diarrhea adversely affects growth and sometimes results in mortality, leading to severe economic losses to the cattle industry. Antibiotics are useful in the treatment against bacterial diarrhea, but not against viral, protozoan, and antibiotic-resistant bacterial diarrhea. Therefore, there are growing requirements for a novel control method for calf diarrhea. Probiotics have been considered promising candidates for preventive and supportive therapy for calf diarrhea for many years. A recent study has revealed that Lactiplantibacillus plantarum HOKKAIDO strain (Lp-HKD) reduces intestinal pathology and the severity of diarrhea in bovine rotavirus (BRV)-infected calves. Lp-HKD is known to enhance the function of human immune cells and expected to be used as probiotics for humans. Therefore, it is hypothesized that Lp-HKD modulates antiviral immune response in cattle and provide the clinical benefits in BRV-infected calves. However, the detailed mechanism of Lp-HKD-induced immunomodulation remains unknown. Thus, this study aimed to elucidate the immunomodulatory and antiviral effects of Lp-HKD in cattle. Cultivation assay of bovine peripheral blood mononuclear cells (PBMCs) showed that live and heat-killed Lp-HKD stimulates the production of interleukin-1β (IL-1β), IL-6, IL-10, and interferon-γ (IFN-γ) from PBMCs. Stimulation by heat-killed Lp-HKD yielded stronger cytokine production than stimulation by the live Lp-HKD. Additionally, CD14+ monocytes were identified as major producers of IL-1β, IL-6, and IL-10 under Lp-HKD stimulation; however, IFN-γ was mainly produced from immune cells other than CD14+ monocytes. Depletion of CD14+ monocytes from the PBMCs cultivation strongly decreased cytokine production induced by heat-killed Lp-HKD. The inhibition of toll-like receptor (TLR) 2/4 signaling decreased IL-1β and IL-6 production induced by live Lp-HKD and IL-1β, IL-6, and IFN-γ production induced by heat-killed Lp-HKD. Furthermore, live or heat-killed Lp-HKD also activated T cells and their production of IFN-γ and tumor necrosis factor-α. Then, culture supernatants of bovine PBMCs treated with heat-killed Lp-HKD demonstrated antiviral effects against BRV in vitro. In conclusion, this study demonstrated that Lp-HKD activates the functions of bovine immune cells via TLR2/4 signaling and exerts an antiviral effect against BRV through the induction of antiviral cytokines. Lp-HKD could be useful for the prevention and treatment of calf diarrhea through its immune activating effect.
• Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors.
  Naoya Maekawa; Satoru Konnai; Yumie Asano; Takumi Otsuka; Eri Aoki; Hiroto Takeuchi; Yukinari Kato; Mika K Kaneko; Shinji Yamada; Yumiko Kagawa; Maki Nishimura; Satoshi Takagi; Tatsuya Deguchi; Hiroshi Ohta; Takayuki Nakagawa; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
  PloS one, 18, 1, e0281143, 2023年, ［国際誌］
  英語, 研究論文（学術雑誌）, Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-γ stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.
• Characterization of SpsQ from Staphylococcus pseudintermedius as an affinity chromatography ligand for canine therapeutic antibodies.
  Hiroto Takeuchi; Chie Nakajima; Satoru Konnai; Naoya Maekawa; Tomohiro Okagawa; Masaru Usui; Yutaka Tamura; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  PloS one, 18, 1, e0281171, 2023年, ［国際誌］
  英語, 研究論文（学術雑誌）, Coagulase-positive Staphylococci express protein A, which binds to host antibodies, to evade the immune system. Taking advantage of its specific binding to antibodies, protein A from Staphylococcus aureus, which is called SpA, is commonly used as an affinity chromatography ligand for human therapeutic antibodies. However, among four canine IgG subclasses (A, B, C, and D), only IgG-B binds to SpA strongly and establishing an efficient and robust purification scheme for canine therapeutic antibodies whose IgG subclass is A, C, or D remains difficult and depends on finding a suitable substitute to SpA. S. pseudintermedius, a major coagulase-positive Staphylococci found in dogs, expresses spsQ gene which is orthologous to S. aureus spa. We hypothesized that to serve S. pseudintermedius to better adapt to the dog immune system, SpsQ would bind to canine IgGs stronger than SpA, making it a better affinity chromatography ligand for canine therapeutic antibodies. To characterize SpsQ, we first determined the spsQ nucleotide sequence from S. pseudintermedius isolates. Based on the identified sequence, we prepared recombinant proteins containing the immunoglobulin-binding domains of SpA (r-SpA) and SpsQ (r-SpsQ) and determined their binding capacity for each canine IgG subclass. The binding capacity of r-SpsQ for IgG-B was almost as high as that of r-SpA. Interestingly, while both r-SpsQ and r-SpA showed no binding to IgG-C, the binding capacity of r-SpsQ for IgG-A and IgG-D was significantly higher than that of r-SpA. Finally, we performed affinity chromatography using r-SpsQ- or r-SpA-immobilized resin and revealed that the recovery rates of IgG-A and IgG-D using r-SpsQ were significantly higher than those using r-SpA. Our findings indicate that SpsQ has a strong potential to be used as an affinity chromatography ligand for canine therapeutic antibodies of subclass A, B, and D.
• Prostaglandin E2-Induced Immune Suppression via Cytotoxic T-Lymphocyte Antigen 4 in Paratuberculosis.
  Yamato Sajiki; Satoru Konnai; Kei Watari; Tomohiro Okagawa; Akina Tanaka; Satoko Kawaji; Reiko Nagata; Naoya Maekawa; Yasuhiko Suzuki; Yukinari Kato; Shiro Murata; Yasuyuki Mori; Kazuhiko Ohashi
  Infection and immunity, 90, 10, e0021022, 2022年09月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, Paratuberculosis is a chronic enteritis of ruminants caused by the facultative intracellular pathogen Mycobacterium avium subsp. paratuberculosis. The Th1 response inhibits the proliferation of M. avium subsp. paratuberculosis during the early subclinical stage. However, we have previously shown that immune inhibitory molecules, such as prostaglandin E2 (PGE2), suppress M. avium subsp. paratuberculosis-specific Th1 responses as the disease progresses. To date, the mechanism underlying immunosuppression during M. avium subsp. paratuberculosis infection has not been elucidated. Therefore, in the present study, we investigated the function of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed by peripheral blood mononuclear cells (PBMCs) from cattle with paratuberculosis because CTLA-4 expression is known to be elevated in T cells under an M. avium subsp. paratuberculosis experimental infection. M. avium subsp. paratuberculosis antigen induced CTLA-4 expression in T cells from cattle experimentally infected with M. avium subsp. paratuberculosis. Interestingly, both PGE2 and an E prostanoid 4 agonist also induced CTLA-4 expression in T cells. In addition, a functional assay with a bovine CTLA-4-immunogobulin fusion protein (CTLA-4-Ig) indicated that CTLA-4 inhibited gamma interferon (IFN-γ) production in M. avium subsp. paratuberculosis-stimulated PBMCs, while blockade by anti-bovine CTLA-4 monoclonal antibody increased the secretion of IFN-γ and tumor necrosis factor alpha production in these PBMCs. These preliminary findings show that PGE2 has immunosuppressive effects via CTLA-4 to M. avium subsp. paratuberculosis. Therefore, it is necessary to clarify in the future whether CTLA-4-mediated immunosuppression facilitates disease progression of paratuberculosis in cattle.
• In vitro antibacterial activity of OPS-2071 against Gram-positive and Gram-negative enteropathogenic bacteria.
  Daisuke Oka; Ruchirada Changkwanyeun; Tomoyuki Yamaguchi; Chie Nakajima; Yasuhiko Suzuki; Makoto Matsumoto
  The Journal of antimicrobial chemotherapy, 2022年09月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Enteric infections are a major public health issue in developing countries. Antimicrobial resistance is also a problem for enteric infection. OPS-2071 is a novel quinolone antibiotic with low oral absorption and potent antibacterial activity against Clostridioides difficile. OBJECTIVES: This study was conducted to confirm the antimicrobial activity of OPS-2071 against major enteropathogenic bacteria and to evaluate the risk of emergence of drug resistance. METHODS: The antibacterial activity was evaluated by the agar dilution method. The inhibitory activity against DNA gyrase and topoisomerase IV was determined by supercoiling assay and decatenation assay, respectively. The mutant prevention concentration and frequency of spontaneous resistance were determined by inoculation on drug-containing agar. RESULTS: Compared with the reference drugs, the antibacterial activity of OPS-2071 was more potent against Gram-positive bacteria and Campylobacter jejuni, including quinolone-resistant strains. Against other Gram-negative bacteria, OPS-2071 was comparable to existing quinolones. The inhibitory activities against DNA gyrase with quinolone-resistant mutations closely correlated with the antibacterial activity. Spontaneous resistance to OPS-2071 was not observed in Staphylococcus aureus and Escherichia coli and was lower than that of existing quinolones and higher than that of azithromycin in C. jejuni. The mutant prevention concentration of OPS-2071 was lower than that of tested compounds in S. aureus and C. jejuni and slightly higher than that of existing quinolones in E. coli. CONCLUSIONS: The broad and potent in vitro antibacterial activity and lower risk of drug resistance suggested that OPS-2071 may be useful for enteric infections caused by major pathogens including quinolone-resistant Campylobacter.
• Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance.
  Dipti Shrestha; Bhagwan Maharjan; Jeewan Thapa; Mwangala Lonah Akapelwa; Precious Bwalya; Joseph Yamweka Chizimu; Chie Nakajima; Yasuhiko Suzuki
  Current issues in molecular biology, 44, 9, 4132, 4141, 2022年09月08日, ［国際誌］
  英語, 研究論文（学術雑誌）, Without the proper information on pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis (MTB), PZA is inappropriately recommended for the treatment of both susceptible and multidrug-resistant tuberculosis (MDR-TB) in Nepal. This study aimed to collect information regarding PZA susceptibility in MTB isolates from Nepal by analyzing pncA and its upstream regulatory region (URR). A total of 211 MTB isolates were included in this study. Sequence analysis of pncA and its URR was performed to assess PZA resistance. First-line drug susceptibility testing, spoligotyping, and sequence analysis of rpoB, katG, the inhA regulatory region, gyrA, gyrB, and rrs were performed to assess their association with pncA mutation. Sequencing results reveal that 125 (59.2%) isolates harbored alterations in pncA and its URR. A total of 57 different mutation types (46 reported and 11 novel) were scattered throughout the whole length of the pncA gene. Eighty-seven isolates (41.2%) harbored mutations in pncA, causing PZA resistance in MTB. There was a more significant association of pncA alterations in MDR/pre-extensively drug-resistant (Pre-XDR) TB than in mono-resistant/pan-susceptible TB (p < 0.005). This first report on the increasing level of PZA resistance in DR-TB in Nepal highlights the importance of PZA susceptibility testing before DR-TB treatment.
• ネコ腫瘍組織におけるprogrammed death ligand 1(PD-L1)の発現解析
  青木 絵理; 今内 覚; 前川 直也; 岡川 朋弘; 竹内 寛人; 佐藤 純平; 浅野 裕美恵; 大塚 拓海; 賀川 由美子; 加藤 幸成; 高木 哲; 鈴木 定彦; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 165回, [DI1A, 04], (公社)日本獣医学会, 2022年09月
  日本語
• 消毒薬が抗菌薬耐性プラスミドの選択圧となる可能性の解明
  川端 結; 石川 北斗; 大枝 夏希; 浅井 鉄夫; 中島 千絵; 鈴木 定彦; 福田 昭; 臼井 優
  日本獣医学会学術集会講演要旨集, 165回, [F1P, 03], (公社)日本獣医学会, 2022年09月
  日本語
• ネコ腫瘍組織におけるprogrammed death ligand 1(PD-L1)の発現解析
  青木 絵理; 今内 覚; 前川 直也; 岡川 朋弘; 竹内 寛人; 佐藤 純平; 浅野 裕美恵; 大塚 拓海; 賀川 由美子; 加藤 幸成; 高木 哲; 鈴木 定彦; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 165回, [DI1A, 04], (公社)日本獣医学会, 2022年09月
  日本語
• Molecular characterization of mutations in isoniazid- and rifampicin- resistant Mycobacterium tuberculosis isolated in Thailand.
  Janisara Rudeeaneksin; Benjawan Phetsuksiri; Chie Nakajima; Yukari Fukushima; Worasak Suthachai; Nattakan Tipkrua; Krairerk Suthum; Nasron Jekloh; Supranee Bunchoo; Sopa Srisungngam; Wiphat Klayut; Shigeyuki Hamada; Yasuhiko Suzuki
  Japanese journal of infectious diseases, 2022年08月31日, ［国内誌］
  英語, 研究論文（学術雑誌）, Drug-resistant tuberculosis (TB) is a great challenge in TB control. The frequency and mutation characteristics can imply the efficiency of molecular tests for the rapid detection of TB drug resistance. This study examined the existence of mutations in katG and inhA for isoniazid (INH) resistance, and rpoB for rifampicin (RIF) resistance. A total of 178 drug-resistant Mycobacterium tuberculosis (MTB) isolates were analyzed. Mutations in katG encoding and inhA regulatory regions were detected in 136/168 (81.0%) and 29/168 (17.3%), respectively, with the most prominent mutation of Ser315Thr substitution in katG in 126/168 (75.0%), and -15 C > T substitution in the regulatory region of the inhA (26/168; 15.5%). Two distinct katG mutations (Tyr337Cys, 1003InsG) were identified. Of 125 RIF-resistant isolates, 118 (94.4%) carried mutations affecting the 81-bp RIF resistance-determining region (RRDR) with the most commonly affected codons 450, 445, and 435 identified in 74 (59.2%), 26 (20.8%) and 12 (9.6%) isolates, respectively. The genetic mutations were highly associated with phenotypic INH and RIF resistance, and the majority shared similarities with those in previous studies in Thailand and other Asian countries. The data is useful for guiding the use and the improvement of molecular tests for TB-drug resistance.
• A high-affinity aptamer with base-appended base-modified DNA bound to isolated authentic SARS-CoV-2 strains wild-type and B.1.617.2 (delta variant).
  Hirotaka Minagawa; Hirofumi Sawa; Tomoko Fujita; Shintaro Kato; Asumi Inaguma; Miwako Hirose; Yasuko Orba; Michihito Sasaki; Koshiro Tabata; Naoki Nomura; Masashi Shingai; Yasuhiko Suzuki; Katsunori Horii
  Biochemical and biophysical research communications, 614, 207, 212, 2022年07月23日, ［国際誌］
  英語, 研究論文（学術雑誌）, Simple, highly sensitive detection technologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial for the effective implementation of public health policies. We used the systematic evolution of ligands by exponential enrichment with a modified DNA library, including a base-appended base (uracil with a guanine base at its fifth position), to create an aptamer with a high affinity for the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. The aptamer had a dissociation constant of 1.2 and < 1 nM for the RBD and spike trimer, respectively. Furthermore, enzyme-linked aptamer assays confirmed that the aptamer binds to isolated authentic SARS-CoV-2 wild-type and B.1.617.2 (delta variant). The binding signal was larger that of commercially available anti-SARS-CoV-2 RBD antibody. Thus, this aptamer as a sensing element will enable the highly sensitive detection of SARS-CoV-2.
• Disseminated tuberculosis with paradoxical reactions caused by a Mycobacterium tuberculosis strain belonging to the Indo-Oceanic lineage: An imported case in Japan.
  Kengo Oshima; Chie Nakajima; Kazushige Hirata; Hironori Hayashi; Eiichi N Kodama; Yukari Fukushima; Yasuhiko Suzuki; Hajime Kanamori; Hiroaki Baba; Tetsuji Aoyagi; Koichi Tokuda; Mitsuo Kaku
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 28, 7, 965, 970, 2022年07月, ［国際誌］
  英語, 研究論文（学術雑誌）, Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages.
• Threat from Mycobacterium orygis-associated tuberculosis in south Asia.
  Jeewan Thapa; Stephen V Gordon; Chie Nakajima; Yasuhiko Suzuki
  The Lancet. Microbe, 3, 9, e641-e642, 2022年06月14日, ［国際誌］
  英語, 研究論文（学術雑誌）
• Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy.
  Naoya Maekawa; Satoru Konnai; Yumie Asano; Yamato Sajiki; Tatsuya Deguchi; Tomohiro Okagawa; Kei Watari; Hiroto Takeuchi; Satoshi Takagi; Kenji Hosoya; Sangho Kim; Hiroshi Ohta; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Scientific reports, 12, 1, 9265, 9265, 2022年06月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE2), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE2, interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE2, MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE2 confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE2 suppressed IL-2 and interferon (IFN)-γ production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE2 biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE2 may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy.
• ANTIBIOGRAMS AND VIRULENCE GENES OF ESCHERICHIA COLI AND SALMONELLA SP FROM FARM PIGS IN CENTRAL THAILAND
  Pornthip Chompook; Apiradee Intarapak; Kanjana Changkaew; Ruttana Pachanon; Apichart Suwannachairob; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul; Norikazu Isoda
  Southeast Asian Journal of Tropical Medicine and Public Health, 53, 3, 322, 344, 2022年05月19日
  研究論文（学術雑誌）
• 新たな置換基を1位に保有するキノロン系抗菌薬とらい菌DNAジャイレースの相互作用
  朴 鐘勲; 山口 智之; 会津 勇樹[大内]; 小出 健太郎; Pachanon Ruttana; Chizimu Joseph Yamweka; 森 茂太郎; 金 玄; 向井 徹; 中島 千絵; 鈴木 定彦
  日本ハンセン病学会雑誌, 91, 1, 27, 27, 日本ハンセン病学会, 2022年05月
  日本語
• Molecular Characterization of Mycobacterium ulcerans DNA Gyrase and Identification of Mutations Reducing Susceptibility to Quinolones In Vitro.
  Hyun Kim; Shigetarou Mori; Tsuyoshi Kenri; Yasuhiko Suzuki
  Antimicrobial agents and chemotherapy, 66, 4, e0190221, 2022年04月19日, ［国際誌］
  英語, 研究論文（学術雑誌）, Buruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused by Mycobacterium ulcerans. Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase. However, the detailed molecular basis of these characteristics and the FQ resistance mechanisms in M. ulcerans remains unknown. This study investigated the detailed molecular mechanism of M. ulcerans DNA gyrase and the contribution of FQ resistance in vitro using recombinant proteins from the M. ulcerans subsp. shinshuense and Agy99 strains with reduced sensitivity to FQs. The IC50 of FQs against Ala91Val and Asp95Gly mutants of M. ulcerans shinshuense and Agy99 GyrA subunits were 3.7- to 42.0-fold higher than those against wild-type (WT) enzyme. Similarly, the quinolone concentrations required to induce 25% of the maximum DNA cleavage (CC25) was 10- to 210-fold higher than those for the WT enzyme. Furthermore, the interaction between the amino acid residues of the WT/mutant M. ulcerans DNA gyrase and FQ side chains were assessed by molecular docking studies. This was the first elaborative study demonstrating the contribution of mutations in M. ulcerans DNA GyrA subunit to FQ resistance in vitro.
• Characterisation of plasmids harbouring qnrA1, qnrS1, and qnrB4 in E. coli isolated in the Philippines from food-producing animals and their products.
  Lawrence P Belotindos; Risa Tsunoda; Marvin A Villanueva; Chie Nakajima; Claro N Mingala; Yasuhiko Suzuki
  Journal of global antimicrobial resistance, 30, 38, 46, 2022年04月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Determinants showing plasmid-mediated quinolone resistance, which usually leads to antimicrobial ineffectiveness, have become an emerging clinical problem. In our previous study in the Philippines, a high prevalence of Qnr determinants was found in clinical samples and food-producing animals and their food products. However, no qnr-carrying plasmids have been investigated in animals or animal-derived foods. Hence, in the present, we aimed to characterise qnr-carrying plasmids in Escherichia coli isolated from the food supply chain. METHODS: Plasmids from 44 qnr-positive isolates were assigned to incompatibility groups by PCR-based replicon typing, and the presence of β-lactamase-encoding genes were investigated by PCR. Localisation of qnr in plasmids was determined by S1-PFGE and Southern blot hybridisation. The transferability of qnr-carrying plasmids was examined by conjugation analysis. RESULTS: Overall, 77.3% (95%CI = 62.2 - 88.5) of the isolates harbouring qnr determinants were positive for seven plasmid types, and 56.8% concurrently harboured blaTEM-1. Plasmid IncFrepB was prevalent (65.9%, 95%CI = 50.1 - 79.5) among qnr determinants. Localisation of qnr determinants in IncFrepB and transferability of plasmids was further confirmed. CONCLUSIONS: The current study proved that qnr in E. coli isolated from food-producing animals and their food products could spread via plasmid IncFrepB upon selective pressure with quinolones or other antimicrobials. Therefore, to curb the emergence and spread of qnr-harbouring bacteria in the Philippines, prudent use of antimicrobials in animal production and stricter hygiene and food handling are recommended.
• Campylobacter Express Resistance Array for detecting the presence of fluoroquinolone- and macrolide-resistant Campylobacter jejuni and Campylobacter coli in broiler farms
  Masaru Usui; Junya Tase; Masanobu Onozaki; Yasuhiko Suzuki; Yutaka Tamura; Chie Nakajima
  Journal of Applied Microbiology, 132, 4, 3249, 3255, 2022年04月
  研究論文（学術雑誌）
• Campylobacter Express Resistance Array for detecting the presence of fluoroquinolone- and macrolide-resistant Campylobacter jejuni and Campylobacter coli in broiler farms.
  Masaru Usui; Junya Tase; Masanobu Onozaki; Yasuhiko Suzuki; Yutaka Tamura; Chie Nakajima
  Journal of applied microbiology, 132, 4, 3249, 3255, 2022年04月, ［国際誌］
  英語, 研究論文（学術雑誌）, AIMS: The aim of the study was to develop a microarray-based method for the detection of antibiotic-resistant Campylobacter in broiler farms to decrease the risk of contamination of chicken meat. METHODS AND RESULTS: A combination of DNA microarray and primer extension for rapid and simultaneous detection of fluoroquinolone- and macrolide-resistant Campylobacter jejuni/Campylobacter coli, termed Campylobacter Express Resistance Array (CAMERA), was used to analyse chicken caecal droppings. CAMERA assays could detect at least 105 colony forming units of C. jejuni/C. coli g-1 of chicken caecal contents spiked with C. jejuni/C. coli. To compare the CAMERA method and direct culturing method for screening antibiotic-resistant C. jejuni/C. coli in poultry farms, chicken caecal droppings obtained from 42 poultry houses were analysed using both methods. In total, 95.2% of the results (40/42 poultry houses) obtained using the CAMERA and culturing method were identical. In the remaining two poultry houses, the CAMERA could detect the prevalent strain of C. jejuni/C. coli based on results of the culturing method. CONCLUSIONS: The culturing method required >3 days to isolate and identify antibiotic-resistant C. jejuni/C. coli. In contrast, the CAMERA required only 6 h. SIGNIFICANCE AND IMPACT OF THE STUDY: This method can facilitate quick screening and control of fluoroquinolone- and macrolide-resistant C. jejuni/C. coli in broiler farms.
• Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia
  Precious Bwalya; Eddie S. Solo; Joseph Y. Chizimu; Dipti Shrestha; Grace Mbulo; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Tuberculosis, 133, 2022年03月
  研究論文（学術雑誌）
• Broad-host-range IncW plasmid harbouring tet(X) in Escherichia coli isolated from pigs in Japan.
  Masaru Usui; Akira Fukuda; Yasuhiko Suzuki; Chie Nakajima; Yutaka Tamura
  Journal of global antimicrobial resistance, 28, 97, 101, 2022年03月, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Tetracyclines are used in veterinary medicine for livestock. Tigecycline, a semisynthetic tetracycline derivative, is a last-resort antimicrobial used to treat multidrug-resistant Gram-negative bacterial infections. The prevalence of variants of the mobile tigecycline resistance gene tet(X) in livestock is increasing worldwide. However, the prevalence of Tet(X) among livestock in Japan is unclear. This study was conducted to clarify the prevalence of Tet(X) in pigs in Japan, focusing on isolation and molecular characterisation of plasmid-mediated tet(X)-positive Escherichia coli through retrospective analysis. METHODS: We retrospectively screened for tigecycline-resistant E. coli strains isolated from pigs. The tigecycline-resistant strain and tet(X)-harbouring plasmid were characterised. RESULTS: The IncW plasmid harbouring the tet(X) variant [previously named as tet(X6)] was detected in one E. coli isolate from pigs (0.8%; 1/120) in 2012. The tet(X) plasmid was transferable by conjugation to the E. coli ML4909 recipient strain. Some mobile genetic elements (TnAs3 and ISVsa3) were observed in the region surrounding tet(X). The tet(X)-harbouring plasmid shared a conserved backbone with IncW plasmid R388, which is a broad-host-range plasmid. CONCLUSION: The emergence and spread of tet(X) variants in Enterobacterales poses a public-health concern. To the best of our knowledge, this is the first report of the emergence of an IncW plasmid harbouring tet(X). Using tetracyclines in livestock exerts selective pressure on the tet(X) plasmid; therefore, prudent use of tetracyclines is required.
• Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia.
  Precious Bwalya; Eddie S Solo; Joseph Y Chizimu; Dipti Shrestha; Grace Mbulo; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Tuberculosis (Edinburgh, Scotland), 133, 102184, 102184, 2022年03月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Ethambutol (EMB) is an important anti-tuberculosis drug used in the management of multi-drug resistant tuberculosis (MDR-TB). Mutations in embB are the major mechanism of resistance. This study investigated embB mutations among MDR-TB isolates and analyzed their correlations with phenotypic drug susceptibility testing (DST) in Zambia. METHOD: A total of 132 MDR-TB isolates were collected from January 2014 to April 2017 and characterized using MGIT 960 systems, embB sequencing, and spoligotyping. RESULTS: Out of 61 phenotypically EMB resistant isolates, 53 had mutations in embB. Among the 71 EMB susceptible isolates, 47 had embB mutations. Sensitivity of embB mutations was 86.9% while specificity was 33.8%. CAS1_Kili (SIT21) had high odds of having embB mutations, particularly, G918A (Met306eIl) (Odds ratio 16.7, p < 0.0001). CONCLUSION: Molecular EMB resistance testing by DNA sequencing can improve detection of EMB resistance among MDR-TB patients in Zambia. Additionally, CAS1_Kili was associated with embB amino acid substitution Met306Ile suggesting transmission. A detailed investigation to track and determine transmission hotspot area for MDR-TB could help optimize control strategies.
• Enhancement of interleukin-2 production by bovine peripheral blood mononuclear cells treated with the combination of anti-programmed death-ligand 1 and cytotoxic T lymphocyte antigen 4 chimeric monoclonal antibodies.
  Kei Watari; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Yamato Sajiki; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  The Journal of veterinary medical science, 84, 1, 6, 15, 2022年01月07日, ［国内誌］
  英語, 研究論文（学術雑誌）, Our previous studies demonstrate the therapeutic efficacy against bovine diseases of an anti-bovine programmed death-ligand 1 (PD-L1) chimeric antibody. In humans, PD-1 and PD-L1 antibodies are more effective when combined with an antibody targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and these combination therapies are therefore clinically used. Here we generated an anti-bovine CTLA-4 chimeric antibody (chAb) to enhance the therapeutic efficacy of the PD-L1 antibody. We further analyzed the effects of dual blockade of CTLA-4 and PD-1 pathways on T-cell responses. The established anti-bovine CTLA-4 chAb showed comparable blocking activity on the binding of bovine CTLA-4 to CD80 and CD86 as the anti-bovine CTLA-4 mouse monoclonal antibody. Anti-bovine CTLA-4 chAb also significantly increased IL-2 production from bovine peripheral blood mononuclear cells (PBMCs). Further, the combination of anti-CTLA-4 chAb with anti-PD-L1 chAb significantly upregulated IL-2 production by PBMCs. These results suggest that the combination of antibodies have higher potential to enhance immune responses against pathogens compared with single administration.
• Conjugative IncHI2/HI2A plasmids harbouring mcr-9 in colistin-susceptible Escherichia coli isolated from diseased pigs in Japan.
  Akira Fukuda; Hitomi Nakano; Yasuhiko Suzuki; Chie Nakajima; Masaru Usui
  Access microbiology, 4, 11, acmi000454, 2022年, ［国際誌］
  英語, 研究論文（学術雑誌）, Colistin is a last resort antimicrobial used for the treatment of gram-negative bacterial infections. Plasmid-mediated colistin resistance (mcr) genes are a cause of global concern, and, thus far, mcr-1-10 have been identified. In a previous study, we screened mcr-1-5 in Escherichia coli derived from diseased pigs in Japan and reported a high prevalence of mcr-1, -3 and -5. However, the previous report on the prevalence of mcr genes was inaccurate. In the present study, we aimed to clarify the prevalence of all reported variants of mcr in E. coli derived from the diseased pigs, which were previously screened for mcr-1-5. Additionally, we also characterized the mcr-9-positive E. coli , which was detected in this study. We screened mcr in 120 E. coli strains from diseased pigs and mcr-positive E. coli and an mcr-carrying plasmid were also characterized. One mcr-9-positive colistin-susceptible E. coli strain was detected (0.8 %). Plasmid-mediated mcr-9 was transferred to E. coli ML4909 as the recipient strain, and it was located on IncHI2/HI2A plasmid p387_L with other antimicrobial resistance genes (ARGs). The region harbouring ARGs including mcr-9, was similar to that on the Klebsiella pneumoniae chromosome harbouring mcr-9 isolated in Japan. mcr-3, -5 and -9 were detected (4.2 %) in colistin-susceptible strains. mcr-9 was found to be disseminated via the plasmid IncHI2/HI2A p387_L and transferred and inserted into chromosomes via a transposon. Our results suggest that mcr genes should be monitored regularly, regardless of their susceptibility to colistin.
• Corrigendum: The TbD1 Locus Mediates a Hypoxia-Induced Copper Response in Mycobacterium bovis.
  Ruoyao Ma; Damien Farrell; Gabriel Gonzalez; John A Browne; Chie Nakajima; Yasuhiko Suzuki; Stephen V Gordon
  Frontiers in microbiology, 13, 947450, 947450, 2022年, ［国際誌］
  英語, [This corrects the article DOI: 10.3389/fmicb.2022.817952.].
• The TbD1 Locus Mediates a Hypoxia-Induced Copper Response in Mycobacterium bovis.
  Ruoyao Ma; Damien Farrell; Gabriel Gonzalez; John A Browne; Chie Nakajima; Yasuhiko Suzuki; Stephen V Gordon
  Frontiers in microbiology, 13, 817952, 817952, 2022年, ［国際誌］
  英語, 研究論文（学術雑誌）, The Mycobacterium tuberculosis complex (MTBC) contains the causative agents of tuberculosis (TB) in mammals. The archetypal members of the MTBC, Mycobacterium tuberculosis and Mycobacterium bovis, cause human tuberculosis and bovine tuberculosis, respectively. Although M. tuberculosis and M. bovis share over 99.9% genome identity, they show distinct host adaptation for humans and animals; hence, while the molecular basis of host adaptation is encoded in their genomes, the mechanistic basis of host tropism is still unclear. Exploration of the in vitro phenotypic consequences of known genetic difference between M. bovis and M. tuberculosis offers one route to explore genotype-phenotype links that may play a role in host adaptation. The TbD1 ("Mycobacterium tuberculosis deletion 1 region") locus encompasses the mmpS6 and mmpL6 genes. TbD1 is absent in M. tuberculosis "modern" lineages (Lineages 2, 3, and 4) but present in "ancestral" M. tuberculosis (Lineages 1 and 7), Mycobacterium africanum lineages (Lineages 5 and 6), newly identified M. tuberculosis lineages (Lineages 8 and 9), and animal adapted strains, such as M. bovis. The function of TbD1 has previously been investigated in M. tuberculosis, where conflicting data has emerged on the role of TbD1 in sensitivity to oxidative stress, while the underlying mechanistic basis of such a phenotype is unclear. In this study, we aimed to shed further light on the role of the TbD1 locus by exploring its function in M. bovis. Toward this, we constructed an M. bovis TbD1 knockout (ΔTbD1) strain and conducted comparative transcriptomics to define global gene expression profiles of M. bovis wild-type (WT) and the ΔTbD1 strains under in vitro culture conditions (rolling and standing cultures). This analysis revealed differential induction of a hypoxia-driven copper response in WT and ΔTbD1 strains. In vitro phenotypic assays demonstrated that the deletion of TbD1 sensitized M. bovis to H2O2 and hypoxia-specific copper toxicity. Our study provides new information on the function of the TbD1 locus in M. bovis and its role in stress responses in the MTBC.
• Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia.
  Joseph Yamweka Chizimu; Eddie Samuneti Solo; Precious Bwalya; Thoko Flav Kapalamula; Mwangala Lonah Akapelwa; Patrick Lungu; Dipti Shrestha; Yukari Fukushima; Victor Mukonka; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 114, 142, 150, 2022年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Zambia is among the 30 high tuberculosis burden countries in the world. Despite increasing reports of multidrug-resistant tuberculosis (MDR-TB) in routine surveillance, information on the transmission of MDR Mycobacterium tuberculosis strains is largely unknown. This study elucidated the genetic diversity and transmission of MDR M. tuberculosis strains in Lusaka, Zambia. METHODS: Eighty-five MDR M. tuberculosis samples collected from 2013 to 2017 at the University Teaching Hospital were used. Drug-resistance associated gene sequencing, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), and multiplex PCR for RD-Rio sub-lineage identification were applied. RESULTS: The identified clades were LAM (48%), CAS (29%), T (14%), X (6%) and Harlem (2%). Strains belonging to SITs 21/CAS1-Kili and 20/LAM1 formed the largest clonal complexes. Combined spoligotyping and 24 loci-MIRU-VNTR revealed 47 genotypic patterns with a clustering rate of 63%. Ninety-five percent of LAM strains belonged to the RD-Rio sub-lineage. CONCLUSION: The high clustering rate suggested that a large proportion of MDR-TB was due to recent transmission rather than the independent acquisition of MDR. This spread was attributed to clonal expansion of SIT21/CAS1-Kili and SIT20/LAM1 strains. Therefore, TB control programs recommending genotyping coupled with conventional epidemiological methods can guide measures for stopping the spread of MDR-TB.
• Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia.
  Joseph Yamweka Chizimu; Eddie Samuneti Solo; Precious Bwalya; Wimonrat Tanomsridachchai; Herman Chambaro; Misheck Shawa; Thoko Flav Kapalamula; Patrick Lungu; Yukari Fukushima; Victor Mukonka; Jeewan Thapa; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 11, 1, 2021年12月28日, ［国際誌］
  英語, 研究論文（学術雑誌）, Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (-35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.
• Endobronchial Ultrasonography with a Guide Sheath Transbronchial Biopsy for Diagnosing Peripheral Pulmonary Lesions within or near Fibrotic Lesions in Patients with Interstitial Lung Disease.
  Takayasu Ito; Shotaro Okachi; Tomoki Kimura; Kensuke Kataoka; Yasuhiko Suzuki; Fumie Kinoshita; Keiko Wakahara; Naozumi Hashimoto; Yasuhiro Kondoh
  Cancers, 13, 22, 2021年11月17日, ［国際誌］
  英語, 研究論文（学術雑誌）, In patients with interstitial lung disease (ILD), the most frequent locations of lung cancer are within or near fibrotic lesions. However, the diagnostic yield for peripheral pulmonary lesions (PPLs) within or near fibrotic lesions using endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) may be unsatisfactory compared to that for PPLs distant from fibrotic lesions because of the difficulty in reaching the lesions. Our objectives were to evaluate the yield for PPLs using EBUS-GS TBB according to the proximity of PPLs to fibrotic lesions and to determine factors affecting the yield for PPLs. We retrospectively investigated 323 consecutive lesions using EBUS-GS TBB between 1 November 2014 and 31 December 2016. We identified PPLs with ILD in such lesions. PPLs with ILD were divided into PPLs within or near fibrotic lesions which met the criterion of PPLs, and of fibrotic lesions overlapping each other (PPLs-FL) and those distant from fibrotic lesions, which met the criterion of PPLs and the area of fibrotic lesion not overlapping each other (PPLs-NFL). Of the 323 lesions, 55 were included (31 PPLs-FL and 24 PPLs-NFL). The diagnostic yield for PPLs-FL was significantly lower than for PPLs-NFL (45.2% vs. 83.3%, p = 0.004). Multivariate analysis revealed that PPLs-NFL (odds ratio (OR) = 7.509) and a probe position within the lesion (OR = 4.172) were significant factors affecting diagnostic yield. Lesion's positional relation to fibrotic lesions and the probe position were important factors affecting the successful diagnosis via EBUS-GS TBB in these patients.
• Abnormal blood coagulation and kidney damage in aged hamsters infected with severe acute respiratory syndrome coronavirus 2
  Marumi Ohno; Michihito Sasaki; Yasuko Orba; Toshiki Sekiya; Md Abdul Masum; Osamu Ichii; Tatsuya Sawamura; Akemi Kakino; Yasuhiko Suzuki; Hiroshi Kida; Hirofumi Sawa; Masashi Shingai
  Viruses, 13, 11, 2021年11月, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia.
  Precious Bwalya; Tomoyuki Yamaguchi; Eddie Samuneti Solo; Joseph Yamweka Chizimu; Grace Mbulo; Chie Nakajima; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 10, 10, 2021年09月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.
• Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG.
  Yuki Arimura; Yusuke Minato; Takayuki Wada; Masaaki Nakayama; Ayako Ryumon; Nao Hirata; Chie Nakajima; Yasuhiko Suzuki; Manabu Ato; Kazuo Kobayashi; Naoko Ohara; Seiji Iida; Naoya Ohara
  Microbiology and immunology, 66, 1, 10, 14, 2021年09月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, Mycobacterium tuberculosis, the causative agent of tuberculosis, possess flavin-dependent thymidylate synthase, ThyX. Since thyX is absent in humans and was shown to be essential for M. tuberculosis normal growth, ThyX is thought to be an attractive novel TB drug target. In this study, we assessed thyX essentiality in Mycobacterium bovis BCG strains using CRISPR interference based gene silencing and found that thyX is not essential in an M. bovis BCG Tokyo derivative strain. We successfully constructed a thyX deletion mutant strain from that strain, which reinforces the non-essentiality of thyX under a certain genetic background. This article is protected by copyright. All rights reserved.
• Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan.
  Yukari Fukushima; Toyotaka Sato; Naoyuki Tsukamoto; Chie Nakajima; Yasuhiko Suzuki; Satoshi Takahashi; Shin-Ichi Yokota
  Journal of global antimicrobial resistance, 27, 150, 155, 2021年09月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Fluoroquinolone (FQ)- and third-generation cephalosporin-resistant Escherichia coli are increasing in Japan. In the early 2000s, the FQ-resistant E. coli clone ST131 increased in clinical settings worldwide. It frequently produces extended-spectrum β-lactamases (ESBLs) such as CTX-M. This study aimed to explore the characteristics of FQ-resistant E. coli isolated in Japan during 2008-2009 and 2020. METHODS: We compared FQ-resistant E. coli clinical isolates from urine samples collected in 2020 (151 isolates) with a FQ-resistant E. coli collection isolated in 2008-2009 (42 isolates). Identification of E. coli ST131 clades and blaCTX-M were determined by multiplex PCR. Sequence types of non-ST131 isolates were determined by whole-genome sequencing. RESULTS: Although the prevalence of ST131 was comparable in 2020 (74.2%) and 2008-2009 (78.6%), the subclades differed during the two time periods (C1-nM27: 40.2% in 2008-2009 vs. 78.8% in 2020; C1-M27: 32.1% in 2008-2009 vs. 9.1% in 2020). The incidence of blaCTX-M among ST131 isolates increased from 27.3% in 2008-2009 to 64.3% in 2020. blaCTX-M was found in 80.6% and 93.8% of C1-M27 and C2 in 2020, respectively, and blaCTX-M possession in C1-nM27 increased from 19.2% in 2008-2009 to 40% in 2020. FQ-resistant ST1193 was detected only in 2020 (17.9% of 151 isolates, of which 14.8% possessed blaCTX-M). CONCLUSION: Increased resistance of E. coli to FQs and third-generation cephalosporins in Japan can be attributed to the accumulation of blaCTX-M in C1-nM27 and the increase of C1-M27 and C2 clades with high blaCTX-M possession, alongside the spread of ST1193.
• Genome Sequences of Two Mycobacterium tuberculosis Isolates from Asian Elephants in Nepal.
  Sarad Paudel; Evan P Brenner; Syeda A Hadi; Yasuhiko Suzuki; Chie Nakajima; Toshio Tsubota; Kamal Prasad Gairhe; Bhagwan Maharjan; Srinand Sreevatsan
  Microbiology resource announcements, 10, 36, e0061421, 2021年09月09日, ［国際誌］
  英語, 研究論文（学術雑誌）, This report describes the genome sequences of two Mycobacterium tuberculosis isolates, S1 and S3, recovered from Asian elephants in Nepal. These genome sequences will enhance our understanding of the genomic epidemiology of Mycobacterium tuberculosis in Asian elephants.
• ウシCTLA-4ならびにPD-L1を標的とした抗体併用法による免疫増強効果の検討
  渡 慧; 今内 覚; 岡川 朋弘; 前川 直也; 村田 史郎; 鈴木 定彦; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 164回, [DIO, 4], (公社)日本獣医学会, 2021年09月
  日本語
• 抗菌薬の繰り返し曝露がClostridioides difficileの性状に与える影響の解明
  鈴木 和総; 福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本獣医学会学術集会講演要旨集, 164回, [FO, 37], (公社)日本獣医学会, 2021年09月
  日本語
• Expression and functional analysis of swine PD-1/PD-L1 pathway(和訳中)
  Otgontuya Ganbaatar; 今内 覚; 岡川 朋弘; 野島 裕太郎; 前川 直也; 市川 世識; 小林 篤史; 芝原 友幸; 柳川 洋二郎; 鈴木 定彦; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 164回, [DIO, 3], (公社)日本獣医学会, 2021年09月
  英語
• ウシCTLA-4ならびにPD-L1を標的とした抗体併用法による免疫増強効果の検討
  渡 慧; 今内 覚; 岡川 朋弘; 前川 直也; 村田 史郎; 鈴木 定彦; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 164回, [DIO, 4], (公社)日本獣医学会, 2021年09月
  日本語
• 焼成ホタテ貝殻粉末と石灰窒素による堆肥中の薬剤耐性菌制御の可能性
  江浪 誠俊; 福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本獣医学会学術集会講演要旨集, 164回, [FO, 15], (公社)日本獣医学会, 2021年09月
  日本語
• 市販堆肥における薬剤耐性菌/耐性遺伝子の分布状況の解明
  小南 風佳; 福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本獣医学会学術集会講演要旨集, 164回, [FO, 35], (公社)日本獣医学会, 2021年09月
  日本語
• 抗菌薬の繰り返し曝露がClostridioides difficileの性状に与える影響の解明
  鈴木 和総; 福田 昭; 中島 千絵; 鈴木 定彦; 臼井 優
  日本獣医学会学術集会講演要旨集, 164回, [FO, 37], (公社)日本獣医学会, 2021年09月
  日本語
• Insights into the ancestry evolution of the Mycobacterium tuberculosis complex from analysis of Mycobacterium riyadhense.
  Qingtian Guan; Musa Garbati; Sara Mfarrej; Talal AlMutairi; Thomas Laval; Albel Singh; Shamsudeen Fagbo; Alicia Smyth; John A Browne; Muhammad Amin urRahman; Alya Alruwaili; Anwar Hoosen; Conor J Meehan; Chie Nakajima; Yasuhiko Suzuki; Caroline Demangel; Apoorva Bhatt; Stephen V Gordon; Faisal AlAsmari; Arnab Pain
  NAR genomics and bioinformatics, 3, 3, lqab070, 2021年09月, ［国際誌］
  英語, 研究論文（学術雑誌）, Current evolutionary scenarios posit the emergence of Mycobacterium tuberculosis from an environmental saprophyte through a cumulative process of genome adaptation. Mycobacterium riyadhense, a related bacillus, is being increasingly isolated from human clinical cases with tuberculosis-like symptoms in various parts of the world. To elucidate the evolutionary relationship between M. riyadhense and other mycobacterial species, including members of the M. tuberculosis complex (MTBC), eight clinical isolates of M. riyadhense were sequenced and analyzed. We show, among other features, that M. riyadhense shares a large number of conserved orthologs with M. tuberculosis and shows the expansion of toxin/antitoxin pairs, PE/PPE family proteins compared with other non-tuberculous mycobacteria. We observed M. riyadhense lacks wecE gene which may result in the absence of lipooligosaccharides (LOS) IV. Comparative transcriptomic analysis of infected macrophages reveals genes encoding inducers of Type I IFN responses, such as cytosolic DNA sensors, were relatively less expressed by macrophages infected with M. riyadhense or M. kansasii, compared to BCG or M. tuberculosis. Overall, our work sheds new light on the evolution of M. riyadhense, its relationship to the MTBC, and its potential as a system for the study of mycobacterial virulence and pathogenesis.
• Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockade.
  Otgontuya Ganbaatar; Satoru Konnai; Tomohiro Okagawa; Yutaro Nojima; Naoya Maekawa; Yoshiki Ichikawa; Atsushi Kobayashi; Tomoyuki Shibahara; Yojiro Yanagawa; Hidetoshi Higuchi; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Immunity, inflammation and disease, 9, 4, 1573, 1583, 2021年08月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Chronic infections lead to the functional exhaustion of T cells. Exhausted T cells are phenotypically differentiated by the surface expression of the immunoinhibitory receptor, such as programmed death-1 (PD-1). The inhibitory signal is produced by the interaction between PD-1 and its PD-ligand 1 (PD-L1) and impairs the effector functions of T cells. However, the expression dynamics of PD-L1 and the immunological functions of the PD-1/PD-L1 pathway in chronic diseases of pigs are still poorly understood. In this study, we first analyzed the expression of PD-L1 in various chronic infections in pigs, and then evaluated the immune activation by the blocking assay targeting the swine PD-1/PD-L1 pathway. METHODS: In the initial experiments, anti-bovine PD-L1 monoclonal antibodies (mAbs) were tested for cross-reactivity with swine PD-L1. Subsequently, immunohistochemical analysis was conducted using the anti-PD-L1 mAb. Finally, we assessed the immune activation of swine peripheral blood mononuclear cells (PBMCs) by the blockade with anti-PD-L1 mAb. RESULTS: Several anti-PD-L1 mAbs tested recognized swine PD-L1-expressing cells. The binding of swine PD-L1 protein to swine PD-1 was inhibited by some of these cross-reactive mAbs. In addition, immunohistochemical analysis revealed that PD-L1 was expressed at the site of infection in chronic infections of pigs. The PD-L1 blockade increased the production of interleukin-2 from swine PBMCs. CONCLUSIONS: These findings suggest that the PD-1/PD-L1 pathway could be also involved in immunosuppression in chronic infections in pigs. This study provides a new perspective on therapeutic strategies for chronic diseases in pigs by targeting immunosuppressive pathways.
• Prevalence and Multidrug-Resistance Salmonella in Swine Production Chain in a Central Province, Thailand.
  Kaknokrat Chonsin; Ruchirada Changkwanyeun; Achiraya Siriphap; Apiradee Intarapuk; Watsawan Prapasawat; Kanjana Changkaew; Chaiwat Pulsrikan; Norikazu Isoda; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  Journal of food protection, 84, 12, 2174, 2184, 2021年08月19日, ［国際誌］
  英語, 研究論文（学術雑誌）, Salmonella causes foodborne disease outbreaks worldwide and raises considerable concerns about public health and economic losses. To determine prevalence, serovar, antimicrobial resistance (AMR) patterns, and extended-spectrum beta-lactamase (ESBL) genes, the present cross-sectional study collected a total of 418 fecal, carcass (three slaughterhouses), pork and cutting board (four markets) samples from a province in central Thailand in 2017 and 2018. Results showed that 65.1% (272/418) of samples were positive for Salmonella. The percentage of Salmonella positive samples from markets (88.8%; 158/178) was significantly higher than those from slaughterhouses (47.5%; 114/240) ( P<0.05 ). In total, 1,030 isolates were identified; of these, 409 were assigned to 45 serovars with S. Rissen (20%; 82/409) being the most common. New serovars of Thai isolates, S. Cannstatt and S. Braubach, were identified in market and slaughterhouse samples, respectively. AMR of Salmonella isolates showed that 73.9% (133/180) of 19 different serovars exhibited multidrug resistance (MDR). Screening for ESBL production showed that 10.3% (41/399) of isolates were ESBL positive. ESBL-producing Salmonella isolates in market samples (75.6%; 31/41) were significantly higher than those in slaughterhouse samples (24.4%; 10/41) ( P<0.05 ). In market samples, 77.4% (24/31) were isolated from pork and 22.6% (7/31) from cutting boards. Nine ESBL-producing isolates carried single type ESBL genes bla TEM (9.8%; 4/41) or bla CTX-M (12.2%; 5/41), while 11 (26.8%) carried both bla TEM and bla CTX-M . No ESBL-producing Salmonella isolate carried the gene bla SHV . Results suggest that pigs, their flesh, and cutting boards could be reservoirs for widespread MDR, ESBL-producing Salmonella outbreak across the food chain.
• Tuberculosis seroprevalence and comparison of hematology and biochemistry parameters between seropositive and seronegative captive Asian elephants of Nepal.
  Jeewan Thapa; Susan K Mikota; Kamal Prasad Gairhe; Sarad Paudel; Dinesh Kumar Singh; Ishwari Prasad Dhakal; Chie Nakajima; Yasuhiko Suzuki
  The Journal of veterinary medical science, 83, 8, 1278, 1283, 2021年08月12日, ［国内誌］
  英語, 研究論文（学術雑誌）, We conducted a tuberculosis (TB) serosurveillance program of captive elephants in Nepal and compared hematology and biochemistry parameters between seropositive and seronegative elephants. A total of 153 elephants (male=20, female=133) from four national parks were tested for TB using the ElephantTB STAT-PAK® Assay (ChemBio Diagnostic Systems, Inc., Medford, NY, USA). The mean reported age for 138 elephants was 38.5 years (range 2-71 years). Seroprevalence for TB was 21.56% (33/153). The majority of seropositive elephants were female (n=30) and from Chitwan National Park (n=29). The occurrence of TB seropositive cases in other more remote national parks suggests TB may be widespread among the captive elephant population of Nepal. Hematology and biochemistry analyses were performed on 13 and 22 seropositive elephants, respectively and, nine elephants from a seronegative TB herd for comparison. Hematology parameters (hemoglobin, packed cell volume, platelet, white blood cells, and erythrocyte sedimentation rate) were comparable between the two groups. Total protein, globulin, and lactate dehydrogenase were significantly higher in seronegative elephants, and bilirubin was significantly higher in seropositive elephants whereas blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase/aspartate aminotransferase (GOT/AST), glutamic pyruvic transaminase/alanine aminotransferase (GPT/ALT), gamma glutamyl transferase (GT), and albumin were not significantly different. The range of biochemical parameters that were significantly different between seropositive and seronegative elephants had narrow ranges. Thus, the potential of these parameters as a direct biomarker for TB diagnosis is limited based on the findings in this study. We recommend including blood parameters in future TB surveillance studies.
• Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand.
  Janisara Rudeeaneksin; Benjawan Phetsuksiri; Chie Nakajima; Supranee Bunchoo; Krairerk Suthum; Nattakan Tipkrua; Yukari Fukushima; Yasuhiko Suzuki
  Transactions of the Royal Society of Tropical Medicine and Hygiene, 115, 8, 886, 895, 2021年08月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. METHODS: Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. RESULTS: The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. CONCLUSIONS: Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.
• Complete Genome Sequence of an mcr-10-Possessing Enterobacter roggenkampii Strain Isolated from a Dog in Japan.
  Toyotaka Sato; Masaru Usui; Kazuki Harada; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota
  Microbiology resource announcements, 10, 30, e0042621, 2021年07月29日, ［国際誌］
  英語, 研究論文（学術雑誌）, The complete genome sequence of mcr-10-possessing Enterobacter roggenkampii En37, isolated from a dog in Japan, was determined. mcr-10 was located on a 70,277-bp IncFIB plasmid without any additional antimicrobial resistance genes.
• Evaluation of IS1245 LAMP in Mycobacterium avium and the influence of host-related genetic diversity on its application.
  Mwangala Lonah Akapelwa; Thoko Flav Kapalamula; Yuki Ouchi-Aizu; Bernard Mudenda Hang'ombe; Yukiko Nishiuchi; Stephen V Gordon; Eddie Samuneti Solo; Aki Tamaru; Tomoyasu Nishimura; Naoki Hasegawa; Kozo Morimoto; Yukari Fukushima; Yasuhiko Suzuki; Chie Nakajima
  Diagnostic microbiology and infectious disease, 101, 4, 115494, 115494, 2021年07月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, Early detection and treatment are paramount for the timely control of Mycobacterium avium infections. Herein, we designed a LAMP assay targeting a widely used species-specific marker IS1245 for the rapid detection of M. avium and evaluated its applicability using human (n = 137) and pig (n = 91) M. avium isolates from Japan. The developed assay could detect as low as 1 genome copy of M. avium DNA within 30 minutes. All 91 (100%) M. avium isolates from pigs were detected positive while all other tested bacterial species were negative. Interestingly, among the 137 clinical M. avium isolates, 41 (30%) were undetectable with this LAMP assay as they lacked IS1245, the absence of which was revealed by PCR and whole-genome sequencing. These findings highlighted genotypic differences in M. avium strains from humans and pigs in Japan and how this diversity can influence the applicability of a detection tool across different geographic areas and hosts.
• Complete Genome Sequence of an mcr-9-Possessing Enterobacter asburiae Strain Isolated from a Cat in Japan.
  Toyotaka Sato; Masaru Usui; Kazuki Harada; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota
  Microbiology resource announcements, 10, 26, e0028121, 2021年07月, ［国際誌］
  英語, 研究論文（学術雑誌）, We report the complete genome sequence of the mcr-9-possessing strain Enterobacter asburiae En30, isolated from a cat in Japan. The genome sequence was obtained by using long- and short-read sequencing.
• Interaction of Quinolones Carrying New R1 Group with Mycobacterium leprae DNA Gyrase.
  Jong-Hoon Park; Tomoyuki Yamaguchi; Yuki Ouchi; Kentaro Koide; Ruttana Pachanon; Joseph Yamweka Chizimu; Shigetarou Mori; Hyun Kim; Tetsu Mukai; Chie Nakajima; Yasuhiko Suzuki
  Microbial drug resistance (Larchmont, N.Y.), 27, 12, 1616, 1623, 2021年06月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae and the treatment of choice is ofloxacin (OFX). Specific amino acid substitutions in DNA gyrase of M. leprae have been reported leading to resistance against the drug. In our previous study, WQ-3810, a fluoroquinolone with a new R1 group (6-amino-3,5-difluoropyridin-2-yl) was shown to have a strong inhibitory activity on OFX-resistant DNA gyrases of M. leprae, and the structural characteristics of its R1 group was predicted to enhance the inhibitory activity. Methodology/Principal Finding: To further understand the contribution of the R1 group, WQ-3334 with the same R1 group as WQ-3810, WQ-4064, and WQ-4065, but with slightly modified R1 group, were assessed on their activities against recombinant DNA gyrase of M. leprae. An in silico study was conducted to understand the molecular interactions between DNA gyrase and WQ compounds. WQ-3334 and WQ-3810 were shown to have greater inhibitory activity against M. leprae DNA gyrase than others. Furthermore, analysis using quinolone-resistant M. leprae DNA gyrases showed that WQ-3334 had greater inhibitory activity than WQ-3810. The R8 group was shown to be a factor for the linkage of the R1 groups with GyrB by an in silico study. Conclusions/Significance: The inhibitory effect of WQ compounds that have a new R1 group against M. leprae DNA gyrase can be enhanced by improving the binding affinity with different R8 group molecules. The information obtained by this work could be applied to design new fluoroquinolones effective for quinolone-resistant M. leprae and other bacterial pathogens.
• Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance.
  Aleksandr Ilinov; Akihito Nishiyama; Hiroki Namba; Yukari Fukushima; Hayato Takihara; Chie Nakajima; Anna Savitskaya; Gebremichal Gebretsadik; Mariko Hakamata; Yuriko Ozeki; Yoshitaka Tateishi; Shujiro Okuda; Yasuhiko Suzuki; Yuri S Vinnik; Sohkichi Matsumoto
  Scientific reports, 11, 1, 10953, 10953, 2021年05月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles outside the cells as extracellular DNA (eDNA), which is an essential component of biofilm formation and hence antibiotic tolerance. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria's eDNA. Here we found that eDNA is present in slow-growing mycobacterial pathogens, such as Mycobacterium tuberculosis, M. intracellulare, and M. avium at exponential growth phase. In contrast, eDNA is little in all tested rapid-growing mycobacteria. The physiological impact of disrupted eDNA on slow-growing mycobacteria include reduced pellicle formation, floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA necessary for biofilm formation and drug tolerance in slow-growing mycobacteria.
• Rapid and Simple Detection of Isoniazid-Resistant Mycobacterium tuberculosis Utilizing a DNA Chromatography-Based Technique.
  Takuya Kodera; Tomoyuki Yamaguchi; Yukari Fukushima; Kumi Kobayashi; Yutaka Takarada; Joseph Yamweka Chizimu; Chie Nakajima; Eddie Samuneti Solo; Patrick Saili Lungu; Mitsuo Kawase; Yasuhiko Suzuki
  Japanese journal of infectious diseases, 74, 3, 214, 219, 2021年05月24日, ［国内誌］
  英語, 研究論文（学術雑誌）, Despite the availability of anti-tuberculosis drugs, the treatment of tuberculosis has been complicated by drug-resistant tuberculosis. The early detection of drug resistance makes early treatment possible. However, the available tools are mainly for rifampicin resistance detection, and the existing isoniazid resistance detection method is expensive, highly technical, and complicated, making it unsustainable for use in developing nations. This study aimed to develop a simple, rapid, and low-cost diagnostic kit for isoniazid-resistant tuberculosis using the single-stranded tag hybridization method to target an isoniazid resistance-conferring mutation. Specificity and sensitivity were assessed using DNA extracted from 49 isoniazid-resistant and 41 isoniazid-susceptible Mycobacterium tuberculosis clinical isolates cultured in mycobacterial growth indicator tubes. Positive signals were observed on mutant and wild-type lines with 100% sensitivity and specificity compared with Sanger sequencing results. In contrast, no positive signal was observed for non-tuberculosis mycobacteria. The detection limit of this method was 103 CFU or less. The STH-PAS system for isoniazid-resistant M. tuberculosis detection developed in this study offers a better alternative to conventional phenotypic isoniazid resistance determination, which will be of both clinical and epidemiological significance in resource-limited nations.
• Rapid and simultaneous detection of fluoroquinolone- and macrolide-resistant Campylobacter jejuni/coli in retail chicken meat using CAMpylobacter Express Resistance Array (CAMERA)
  Masaru Usui; Sho Tateno; Masanobu Onozaki; Naoaki Misawa; Yasuhiko Suzuki; Yutaka Tamura; Chie Nakajima
  Food Control, 123, 107815, 107815, Elsevier BV, 2021年05月
  研究論文（学術雑誌）
• Genetic characterization of coliform bacterial isolates from environmental water in Thailand.
  Risa Tsunoda; Masaru Usui; Chie Tagaki; Akira Fukuda; Chanchai Boonla; Wilai Anomasiri; Nop Sukpanyatham; Mwangala Lonah Akapelwa; Chie Nakajima; Yutaka Tamura; Yasuhiko Suzuki
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 27, 5, 722, 728, 2021年05月, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: In contrast to the study in other part of the world, information about characteristics of plasmids carrying antimicrobial resistance genes (ARGs) in Enterobacteriaceae derived from environmental water in tropical Asian countries including Thailand is limited. This study, therefore, aimed to gain insight into genetic information of antimicrobial resistance in environmental water in Thailand. METHODS: Coliform bacteria were isolated from environmental water collected at 20 locations in Thailand and identified. Then, susceptibility profiles to ampicillin, cefazoline, cefotaxime, kanamycin, ciprofloxacin, sulfamethoxazole, tetracycline, and nalidixic acid were assessed. In addition, antimicrobial resistant genes integrons, and replicon types were analyzed. And furthermore, plasmids carrying blaTEM and tetM were identified by S1-PFGE analysis and confirmed transmissibility by transconjugation experiments. RESULTS: In 130 coliform bacteria isolated, 89 were resistant to cefazoline while 41 isolates were susceptible. Cefazoline-resistant coliform bacteria were found to be significantly resistant to cefotaxime and tetracycline as compared to susceptible isolates. Hence, blaTEM and tetM correlating with β-lactam antibiotics and tetracycline, respectively, were analyzed found to co-localize on the IncFrepB plasmids in isolates from pig farms' wastewater by S1-PFGE analysis. And furthermore, transmissibility of the plasmids was confirmed. CONCLUSIONS: Results obtained in this study suggested that ARGs in coliform bacteria may have been spreading on the farm via IncFrepB plasmids. Hence, appropriate use of antimicrobials and good hygiene management on the farm are required to prevent the emergence and spread of resistant bacteria.
• First report of Mycobacterium bovis in wild chacma baboons (Papio ursinus) at the human-wildlife interface area in Zambia.
  David Squarre; Joseph Chizimu; Chie Nakajima; John B Muma; Bernard M Hang'ombe; Edgar Simulundu; Wizaso Mwasinga; Jackson Katampi; Paul Fandamu; Victor Mukonka; Yasuhiko Suzuki; Hirofumi Sawa; Hetron M Munang'andu; Griffin Shanungu; Herman M Chambaro; Musso Munyeme
  Transboundary and emerging diseases, 69, 3, 1659, 1662, 2021年04月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, Mycobacterium bovis (M. bovis) causes tuberculosis in mammals and is a major public health threat worldwide. While M. bovis has been reported in humans, domestic and wild ruminants at the human-wildlife-livestock interface area in Zambia, there is paucity of information on the role of primates as reservoir hosts. We screened seven wild chacma baboons (Papio ursinus) for tuberculosis at the human-wildlife interface area in Lochinvar National Park in the Kafue Flats, Zambia. Following necropsy, lung tissue and associated lymph nodes with tuberculous-like lesions collected from four adult male baboons were prepared for Mycobacterium culture. The isolates were initially typed using the Mycobacterium tuberculosis complex-discrimination multiplex PCR assay and further characterized by spoligotyping and 26-loci MIRU-VNTR. Mycobacteria were isolated from all four animals and identified as M. bovis by PCR. On Spoligotyping, all isolates belonged to SB 0120 spoligotype, which is similar to what was previously reported in humans, cattle and Kafue lechwe antelopes in Kafue Flats ecosystem. Furthermore, on MIRU-VNTR typing, the baboon isolates clustered with cattle and Kafue lechwe isolates from the same catchment area. This finding intimates probable cross-species transmission of M. bovis in the Kafue Flats ecosystem. Due to the close interaction of baboons and humans at interface areas in Zambia, our results have potential implications for public health. Equally, this finding raises concerns for conservation.
• Molecular epidemiology of Mycobacterium bovis in central parts of Malawi.
  Thoko Flav Kapalamula; Joseph Chizimu; Lawrence Belotindos; Mwangala Akapelwa; Dipti Shrestha; Mirriam Ethel Nyenje; Musso Munyeme; Bernard Mudenda Hang'ombe; Rajhab Sawasawa Mkakosya; Stephen V Gordon; Chie Nakajima; Yasuhiko Suzuki
  Transboundary and emerging diseases, 69, 3, 1577, 1588, 2021年04月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine tuberculosis (bTB) is a neglected disease that affects cattle and humans. The burden of bTB is higher in developing countries as compared to industrialized countries. The reasons behind this discrepancy include the fact that bTB control measures, such as testing and slaughter of infected cattle and pasteurization of milk, are not usually practised in developing countries largely because of their high cost. To improve our understanding of bTB in developing countries, molecular typing studies are essential, in particular in terms of transmission dynamics, infection sources and knowledge of circulating strains of the principal causative agent, Mycobacterium bovis. In this study, we applied a suite of molecular typing techniques encompassing deletion analysis, spoligotyping and MIRU-VNTR to isolates recovered from samples collected during the routine post-mortem of cattle at the cold storage abattoir in Lilongwe, Malawi. Out of 63 isolates, 51 (81%) belonged to the European 1. M. bovis clonal complex. Spoligotyping identified 8 profiles, with SB0131 being the predominant type (56% of isolates). Spoligotypes SB0273 and SB0425 were identified in 14% and 13%, respectively, of the isolates. MIRU-VNTR showed a high discriminatory power of 0.959 and differentiated the 8 spoligotypes to 31 genotypes. The high diversity of M. bovis within the study area suggests the infection has been circulating in the area for a considerable period of time, likely facilitated by the lack of effective control measures. We also observed genetic similarities between isolates from Malawi (this study) to isolates described in previous studies in Zambia and Mozambique, suggesting transmission links in this region. The information provided by this study provides much needed evidence for the formulation of improved bTB control strategies.
• Amino Acid Substitution Ser83Ile in GyrA of DNA Gyrases Confers High-Level Quinolone Resistance to Nontyphoidal Salmonella Without Loss of Supercoiling Activity.
  Kentaro Koide; Lai Lai San; Ruttana Pachanon; Jong-Hoon Park; Yuki Ouchi; Siriporn Kongsoi; Fuangfa Utrarachkij; Chie Nakajima; Yasuhiko Suzuki
  Microbial drug resistance (Larchmont, N.Y.), 27, 10, 1397, 1404, 2021年04月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, Aims: Quinolone-resistant nontyphoidal Salmonella having serine replaced by isoleucine at the 83rd amino acid in GyrA (GyrA-Ser83Ile) has recently been found in Asian countries. In this study, we aimed to examine the direct effect of substitution Ser83Ile on DNA gyrase activity and/or resistance to quinolones. Materials and Methods: Using 50% of the maximal inhibitory concentrations (IC50s) of quinolones, recombinant wild type (WT) and seven mutant DNA gyrases having amino acid substitutions, including Ser83Ile, were screened for enzymatic activity that causes supercoils in relaxed plasmid DNA and resistance to quinolones. Results: Little differences in supercoiling activity were observed between WT and mutant DNA gyrases. By contrast, the IC50s of ciprofloxacin and norfloxacin against GyrA-Ser83Ile/GyrB-WT were 11.6 and 73.3 μg/mL, respectively, which were the highest used against the DNA gyrases examined in this study. Conclusion: Ser83Ile in GyrA was shown to confer high-level quinolone resistance to DNA gyrases of nontyphoidal Salmonella, with no loss of supercoiling activity. Salmonella strain carrying GyrA with Ser83Ile may emerge under a high-concentration pressure of quinolones and easily spread even with no selection bias by quinolones. Hence, avoiding the overuse of quinolones is needed to prevent the spread of Salmonella with Ser83Ile in GyrA.
• Effectiveness of Fluoroquinolones with Difluoropyridine Derivatives as R1 Groups on the Salmonella DNA Gyrase in the Presence and Absence of Plasmid-Encoded Quinolone Resistance Protein QnrB19.
  Ruttana Pachanon; Kentaro Koide; Siriporn Kongsoi; Nami Ajima; Thoko Flav Kapalamula; Chie Nakajima; Orasa Suthienkul; Yasuhiko Suzuki
  Microbial drug resistance (Larchmont, N.Y.), 27, 10, 1412, 1419, 2021年04月09日, ［国際誌］
  英語, 研究論文（学術雑誌）, Aims: WQ-3810 has strong inhibitory activity against Salmonella and other fluoroquinolone-resistant pathogens. The unique potentiality of this is attributed to 6-amino-3,5-difluoropyridine-2-yl at R1 group. The aim of this study was to examine WQ-3810 and its derivatives WQ-3334 and WQ-4065 as the new drug candidate for wild-type Salmonella and that carrying QnrB19. Materials and Methods: The half maximal inhibitory concentrations (IC50s) of WQ-3810, WQ-3334 (Br atom in place of methyl group at R8), and WQ-4065 (6-ethylamino-3,5-difluoropyridine-2-yl in place of 6-amino-3,5-difluoropyridine-2-yl group at R1) in the presence or absence of QnrB19 were assessed by in vitro DNA supercoiling assay utilizing recombinant DNA gyrase and QnrB19. Results: IC50s of WQ-3810, WQ-3334, and WQ-4065 against Salmonella DNA gyrase were 0.031 ± 0.003, 0.068 ± 0.016, and 0.72 ± 0.39 μg/mL, respectively, while QnrB19 increased IC50s of WQ-3810, WQ-3334, and WQ-4065 to 0.44 ± 0.05, 0.92 ± 0.34, and 9.16 ± 2.21 μg/mL, respectively. Conclusion: WQ-3810 and WQ-3334 showed stronger inhibitory activity against Salmonella Typhimurium DNA gyrases than WQ-4065 even in the presence of QnrB19. The results suggest that 6-amino-3,5-difluoropyridine-2-yl group at R1 is playing an important role and WQ-3810 and WQ-3334 to be good candidates for Salmonella carrying QnrB19.
• Prevalence and Characterization of Quinolone-Resistance Determinants in Escherichia coli Isolated from Food-Producing Animals and Animal-Derived Food in the Philippines.
  Lawrence Belotindos; Marvin Villanueva; Joel Miguel Jr; Precious Bwalya; Tetsuya Harada; Ryuji Kawahara; Chie Nakajima; Claro Mingala; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 10, 4, 2021年04月09日, ［国際誌］
  英語, 研究論文（学術雑誌）, Antimicrobial resistance to quinolones, which constitutes a threat to public health, has been increasing worldwide. In this study, we investigated the prevalence of quinolone-resistant determinants in Escherichia coli not susceptible to quinolones and isolated from food-producing animals and food derived from them, in the Philippines. A total of 791 E. coli strains were isolated in 56.4% of 601 beef, chicken, pork, egg, and milk samples, as well as environmental, cloacal, and rectal swab-collected samples from supermarkets, open markets, abattoirs, and poultry, swine, and buffalo farms. Using the disc diffusion method, it was determined that 78.6% and 55.4% of the isolates were resistant to at least one antimicrobial and multiple drugs, respectively. In 141 isolates not susceptible to quinolones, 115 (81.6%) harbored quinolone-resistant determinants and had mutations predominantly in the quinolone-resistance determining regions (QRDRs) of gyrA and parC. Plasmid-mediated, quinolone resistance (PMQR) and Qnr family (qnrA1, qnrB4, and qnrS1) genes were detected in all isolates. Forty-eight sequence types were identified in isolates harboring mutations in QRDR and/or PMQR genes by multilocus sequence typing analysis. Moreover, 26 isolates harboring mutations in QRDR and/or PMQR genes belonged mostly to phylogroup B1 and Enteroaggregative E. coli. In conclusion, a high prevalence of E. coli was found in food-producing animals and products derived from them, which could potentially spread high-risk clones harboring quinolone-resistance determinants.
• Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease.
  Yoshitaka Tateishi; Yuriko Ozeki; Akihito Nishiyama; Mari Miki; Ryoji Maekura; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Sohkichi Matsumoto
  BMC microbiology, 21, 1, 103, 103, 2021年04月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Mycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated. RESULTS: In this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies. CONCLUSIONS: Our data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.
• Evaluation of Xpert MTB/RIF with microscopy and culture for the diagnosis of tuberculosis in a referral laboratory in Nepal.
  Bhagwan Maharjan; Jeewan Thapa; Dhirendra Kumar Shah; Bhabana Shrestha; Korkut Avsar; Yasuhiko Suzuki; Chie Nakajima
  Japanese journal of infectious diseases, 74, 6, 517, 521, 2021年03月31日, ［国内誌］
  英語, 研究論文（学術雑誌）, Sputum microscopy and Xpert MTB/RIF are the primary rapid diagnostic methods for tuberculosis (TB) in Nepal. Disagreements among Xpert, microscopy, and culture, for example, cases with Xpert positive and microscopy negative, were frequently observed in Nepal including in our reference laboratory. The objective of this study was to compare the effectiveness of Xpert with culture and microscopy for TB diagnosis in Nepal. A total of 125 TB suspected sputum samples were processed for Xpert, microscopy, and culture. The Xpert results when compared with culture showed 100% sensitivity and 97.4% specificity with an excellent agreement (kappa = 0.96), whereas microscopy showed the sensitivity and specificity of 43.2% and 98.7%, respectively, with a moderate agreement (kappa = 0.4). The sensitivity and specificity of microscopy, when compared with Xpert, were 43.5% and 100%, respectively. The majority of Xpert positive samples of a medium MTB detection and all samples of low and very low MTB detection were missed by microscopy. Our study showed that Xpert MTB/RIF is a reliable tool for the diagnosis and management of TB in Nepal. Because of its high cost and sustainability, alternative simple and rapid diagnostic methods with a similar efficiency would be helpful for TB control in Nepal.
• The enhancement of Th1 immune response by anti-PD-L1 antibody in cattle infected with Mycobacterium avium subsp. paratuberculosis.
  Yamato Sajiki; Satoru Konnai; Reiko Nagata; Satoko Kawaji; Hayato Nakamura; Sotaro Fujisawa; Tomohiro Okagawa; Naoya Maekawa; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Yasuyuki Mori; Kazuhiko Ohashi
  The Journal of veterinary medical science, 83, 2, 162, 166, 2021年02月25日, ［国内誌］
  英語, 研究論文（学術雑誌）, Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic enteritis of ruminants. Previous studies have shown that programmed death-ligand 1 (PD-L1) is associated with the disease progression, and PD-L1 blockade activates MAP-specific Th1 responses in vitro. Here, we performed anti-PD-L1 antibody administration using 2 MAP-infected cattle at the late subclinical stage of infection. After administration, bacterial shedding was reduced or maintained at a low level. Additionally, MAP-specific Th1 cytokine production was upregulated, and CD69 expression was increased in T cells. Collectively, the treatment has a potential as a novel control method against Johne's disease.
• Antimicrobial Resistance and Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolated from Slaughtered Pigs and Pork in the Central Region of Thailand.
  Wimonrat Tanomsridachchai; Kanjana Changkaew; Ruchirada Changkwanyeun; Watsawan Prapasawat; Apiradee Intarapuk; Yukari Fukushima; Nattapong Yamasamit; Thoko Flav Kapalamula; Chie Nakajima; Orasa Suthienkul; Yasuhiko Suzuki
  Antibiotics (Basel, Switzerland), 10, 2, 2021年02月19日, ［国際誌］
  英語, 研究論文（学術雑誌）, Methicillin-resistant Staphylococcus aureus (MRSA) have been a major public health concern in humans. Among MRSA, livestock-associated (LA)-MRSA strains have always been associated with exposure to livestock or their products and have emerged in different countries globally. Although studies have identified LA-MRSA from healthy pigs and pork in Thailand, prevalence in slaughtered pigs is still unknown. In addition, there are few reports on the epidemiology and molecular characteristics of LA-MRSA in Thailand. Hence, this is the first report investigating the epidemiology and molecular characteristics of MRSA in individual slaughtered pigs and pork in Thailand. A total of 204 nasal swab and 116 retailed pork samples were collected from three slaughterhouses and four fresh markets, respectively. Individual samples were used for screening for MRSA and obtained isolates were examined for drug- resistance profiling for 12 antimicrobial agents of 10 drug classes. In addition, SCCmec typing and multi-locus sequence typing were conducted to obtain genotype profiles. MRSA were isolated from 11 and 52 nasal swab and pork samples, respectively. The prevalence was significantly higher in the pork than in the nasal swab samples (p-value < 0.05). A high prevalence of ST9-SCCmecIX and ST398-SCCmecV with high-level antimicrobial resistance from markets and slaughterhouses indicated the spreading of MRSA with these genotypes in the Thai swine processing chains and suggested the need for further investigation to determine a control.
• PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma.
  Naoya Maekawa; Satoru Konnai; Maki Nishimura; Yumiko Kagawa; Satoshi Takagi; Kenji Hosoya; Hiroshi Ohta; Sangho Kim; Tomohiro Okagawa; Yusuke Izumi; Tatsuya Deguchi; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Mikihiro Toda; Chie Nakajima; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  NPJ precision oncology, 5, 1, 10, 10, 2021年02月12日, ［国際誌］
  英語, 研究論文（学術雑誌）, Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.
• Characterization of Vibrio parahaemolyticus strains isolated from clinically asymptomatic seafood workers.
  Kaknokrat Chonsin; Neunghatai Supha; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  FEMS microbiology letters, 368, 1, 2021年01月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, Vibrio parahaemolyticus (VP) is a major cause of gastroenteritis outbreaks in Thailand and other countries due to the consumption of contaminated and undercooked seafood. However, there have been few reports of the molecular epidemiology of VP isolates from asymptomatic seafood handlers. Here, we report the phenotypic and genetic characterization of 61 VP isolates obtained from asymptomatic workers in two seafood-processing plants. We found 24 O:K serotypes, of which O11:KUT, O1:KUT and O3:KUT were the dominant serotypes. Analysis by PCR showed that 12 isolates harbored either tdh or trh genes with the potential to be pathogenic VP strains. The presence of T3SS2α and T3SS2β genes was correlated with the presence of tdh and trh, respectively. Four tdh+ isolates were positive for pandemic marker. In this study, VP isolates were commonly resistant to ampicillin, cephazolin, fosfomycin and novobiocin. Phylogenetic analysis of VP1680 loci in 35 isolates from 17 asymptomatic workers, 6 gastroenteritis patients, 7 environmental samples and 5 genomes from a database showed 22 different alleles. Gene VP1680 was conserved in tdh+ isolates and pandemic strains, while that of trh + isolates was diverse. Asymptomatic workers carrying VP were the most likely source of contamination, which raises concerns over food safety in seafood-processing plants.
• Aerobic Composting and Anaerobic Digestion Decrease the Copy Numbers of Antibiotic-Resistant Genes and the Levels of Lactose-Degrading Enterobacteriaceae in Dairy Farms in Hokkaido, Japan.
  Satoshi Katada; Akira Fukuda; Chie Nakajima; Yasuhiko Suzuki; Takashi Azuma; Ayaka Takei; Hideshige Takada; Eiryu Okamoto; Toshihide Kato; Yutaka Tamura; Masaru Usui
  Frontiers in microbiology, 12, 737420, 737420, 2021年, ［国際誌］
  英語, 研究論文（学術雑誌）, Efficient methods for decreasing the spread of antimicrobial resistance genes (ARGs) and transfer of antimicrobial-resistant bacteria (ARB) from livestock manure to humans are urgently needed. Aerobic composting (AC) or anaerobic digestion (AD) are widely used for manure treatment in Japanese dairy farms. To clarify the effects of AC and AD on antimicrobial resistance, the abundances of antimicrobial (tetracycline and cefazolin)-resistant lactose-degrading Enterobacteriaceae as indicator bacteria, copy numbers of ARGs (tetracycline resistance genes and β-lactamase coding genes), and concentrations of residual antimicrobials in dairy cow manure were determined before and after treatment. The concentration of tetracycline/cefazolin-resistant lactose-degrading Enterobacteriaceae was decreased over 1,000-fold by both AC and AD. ARGs such as tetA, tetB, and bla TEM were frequently detected and their copy numbers were significantly reduced by ∼1,000-fold by AD but not by AC. However, several ARG copies remained even after AD treatment. Although concentrations of the majority of residual antimicrobials were decreased by both AC and AD, oxytetracycline level was not decreased after treatment in most cases. In addition, 16S rRNA gene amplicon-based metagenomic analysis revealed that both treatments changed the bacterial community structure. These results suggest that both AC and AD could suppress the transmission of ARB, and AD could reduce ARG copy numbers in dairy cow manure.
• 環境からヒトの生活に侵入する病原微生物 人獣共通感染症としての結核と非定型抗酸菌症
  中島 千絵; 鈴木 定彦
  日本化学療法学会雑誌, 69, 1, 50, 50, (公社)日本化学療法学会, 2021年01月
  日本語
• A TLR7 agonist activates bovine Th1 response and exerts antiviral activity against bovine leukemia virus.
  Yamato Sajiki; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Hayato Nakamura; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Developmental and comparative immunology, 114, 103847, 103847, 2021年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine leukemia virus (BLV) infection is a bovine chronic infection caused by BLV, a member of the genus Deltaretrovirus. In this study, we examined the immunomodulatory effects of GS-9620, a toll-like receptor (TLR) 7 agonist, in cattle (Bos taurus) and its therapeutic potential for treating BLV infection. GS-9620 induced cytokine production in peripheral blood mononuclear cells (PBMCs) as well as CD80 expression in CD11c+ cells and increased CD69 and interferon (IFN)-γ expressions in T cells. Removing CD11c+ cells from PBMCs decreased CD69 expression in T cells in the presence of GS-9620. These results suggest that TLR7 agonism promotes T-cell activation via CD11c+ cells. Analyses using PBMCs from BLV-infected cattle revealed that TLR7 expression in CD11c+ cells was upregulated during late-stage BLV infection. Furthermore, GS-9620 increased IFN-γ and TNF-α production and inhibited syncytium formation in vitro, suggesting that GS-9620 may be used to treat BLV infection.
• Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia.
  Eddie Samuneti Solo; Yasuhiko Suzuki; Trevor Kaile; Precious Bwalya; Patrick Lungu; Joseph Yamweka Chizimu; Yogendra Shah; Chie Nakajima
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 102, 489, 496, 2021年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: The burden of multidrug-resistant tuberculosis (MDR-TB) has been reported to be increasing in Zambia. The reasons for the increase are still unclear. This study determined the diversity of Mycobacterium tuberculosis genotypes among isolates in Lusaka, the capital city, and investigated their association with MDR-TB. METHODS: Spoligotyping, large sequence polymorphism (LSP) analysis, and sequencing of MDR associated genes were performed on a total of 274 M. tuberculosis clinical isolates stored at the University Teaching Hospital from 2013 to 2017. Of these, 134 were MDR-TB while 126 were pan-susceptible. RESULTS: Spoligotyping showed the LAM family as the most predominant genotype (149/274, 54.4%) followed by the CAS family (44/274, 16.1%), T family (39/274, 14.2%), and minor proportions of X, S, Harleem, EAI and Beijing spoligofamilies were identified. Three M. bovis isolates were also observed. Among those, CAS1-Kili (SIT 21) and LAM1 (SIT 20) subfamilies showed a propensity for MDR-TB with p = 0.0001 and p = 0.001, respectively. CONCLUSIONS: This phenomenon might explain the future increase in the MDR-TB burden caused by specific lineages in Zambia. Therefore, it is recommended that the National TB control program in the country complements conventional control strategies with molecular analysis for monitoring and surveillance of MDR-TB epidemiology.
• Development of a loop-mediated isothermal amplification (LAMP) method for specific detection of Mycobacterium bovis.
  Thoko Flav Kapalamula; Jeewan Thapa; Mwangala Lonah Akapelwa; Kyoko Hayashida; Stephen V Gordon; Bernard Mudenda Hang' Ombe; Musso Munyeme; Eddie Samuneti Solo; Precious Bwalya; Mirriam Ethel Nyenje; Aki Tamaru; Yasuhiko Suzuki; Chie Nakajima
  PLoS neglected tropical diseases, 15, 1, e0008996, 2021年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine tuberculosis (TB) caused by Mycobacterium bovis is a significant health threat to cattle and a zoonotic threat for humans in many developing countries. Rapid and accurate detection of M. bovis is fundamental for controlling the disease in animals and humans, and for the proper treatment of patients as one of the first-line anti-TB drug, pyrazinamide, is ineffective against M. bovis. Currently, there are no rapid, simplified and low-cost diagnostic methods that can be easily integrated for use in many developing countries. Here, we report the development of a loop-mediated isothermal amplification (LAMP) assay for specific identification of M. bovis by targeting the region of difference 4 (RD4), a 12.7 kb genomic region that is deleted solely in M. bovis. The assay's specificity was evaluated using 139 isolates comprising 65 M. bovis isolates, 40 M. tuberculosis isolates, seven M. tuberculosis complex reference strains, 22 non-tuberculous mycobacteria and five other bacteria. The established LAMP detected only M. bovis isolates as positive and no false positives were observed using the other mycobacteria and non-mycobacteria tested. Our LAMP assay detected as low as 10 copies of M. bovis genomic DNA within 40 minutes. The procedure of LAMP is simple with an incubation at a constant temperature. Results are observed with the naked eye by a color change, and there is no need for expensive equipment. The established LAMP can be used for the detection of M. bovis infections in cattle and humans in resource-limited areas.
• Canine Transforming Growth Factor-β Receptor 2-Ig: A Potential Candidate Biologic for Melanoma Treatment That Reverses Transforming Growth Factor-β1 Immunosuppression.
  Hiroto Takeuchi; Satoru Konnai; Naoya Maekawa; Satoshi Takagi; Hiroshi Ohta; Noboru Sasaki; Sangho Kim; Tomohiro Okagawa; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Frontiers in veterinary science, 8, 656715, 656715, 2021年, ［国際誌］
  英語, 研究論文（学術雑誌）, Cancer cells can evade host immune systems via multiple mechanisms. Transforming growth factor beta 1 (TGF-β1) is an immunosuppressive cytokine that induces regulatory T cell (Tregs) differentiation and is involved in immune evasion mechanisms in cancer. The inhibition of the TGF-β1 signaling pathway can suppress cancer progression and metastasis through the modulation of anticancer immune responses. However, to best of our knowledge, no implementation of treatments targeting TGF-β1 has been reported in dog cancers. This study aimed to examine whether TGF-β1 is upregulated in canine cancers. We measured TGF-β1 concentrations in culture supernatants of canine melanoma cell lines and in serum samples from dogs with oral malignant melanoma. TGF-β1 production was observed in several cell lines, and serum TGF-β1 levels were elevated in dogs with oral malignant melanoma. Interestingly, the addition of recombinant TGF-β1 to canine peripheral blood mononuclear cell cultures decreased Th1 cytokine production and increased differentiation of CD4+CD25+Foxp3+ lymphocytes, suggesting that TGF-β1 is immunosuppressive in canine immune systems. We developed a decoy receptor for TGF-β, namely TGF-βRII-Ig, by identifying an open reading frame of the canine TGFBR2 gene. TGF-βRII-Ig was prepared as a recombinant fusion protein of the extracellular region of canine TGF-βRII and the Fc region of canine IgG-B. As expected, TGF-βRII-Ig bound to TGF-β1. In the presence of TGF-β1, the treatment with TGF-βRII-Ig increased Th1 cytokine production and decreased the differentiation of CD4+CD25+Foxp3+ lymphocytes. Our results suggest that TGF-βRII-Ig competitively inhibits the immunosuppressive effects of TGF-β1 and thereby activates immune responses. This study demonstrated the potential of TGF-βRII-Ig as a novel biologic for canine melanoma.
• ERRATUM: Rapid and Simple Detection of Isoniazid-Resistant Mycobacterium tuberculosis Utilizing a DNA Chromatography-Based Technique.
  Takuya Kodera; Tomoyuki Yamaguchi; Yukari Fukushima; Kumi Kobayashi; Yutaka Takarada; Joseph Yamweka Chizimu; Chie Nakajima; Eddie Samuneti Solo; Patrick Saili Lungu; Mitsuo Kawase; Yasuhiko Suzuki
  Japanese journal of infectious diseases, 74, 4, 385, 385, 2021年, ［国内誌］
  英語, 研究論文（学術雑誌）, Volume 74, no.3, p.214-219, 2021. Page 214, affiliation "1TBA Co., LTD, Sendai; 2Hokkaido University Research Center for Zoonosis Control, Sapporo; 3Hokkaido University, GI-CoRE Global Station for Zoonosis Control, Sapporo; 4Zambia National Public Health Institute, Ministry of Health, Lusaka, Zambia; 5Department of Pathology and Microbiology, University Teaching Hospital Ministry of Health, Lusaka, Zambia; and 6Ministry of Health, Ndeke House, Lusaka, Zambia." should read "1TBA Co., LTD, Sendai, Japan; 2Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan; 3Hokkaido University, GI-CoRE Global Station for Zoonosis Control, Sapporo, Japan; 4Zambia National Public Health Institute, Ministry of Health, Lusaka, Zambia; 5Department of Pathology and Microbiology, University Teaching Hospital Ministry of Health, Lusaka, Zambia; and 6Ministry of Health, Ndeke House, Lusaka, Zambia".
• Emergence of the Novel Aminoglycoside Acetyltransferase Variant aac(6')-Ib-D179Y and Acquisition of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Due to a Disrupting Mutation in the DNA Repair Enzyme MutS.
  Toyotaka Sato; Takayuki Wada; Suguru Nishijima; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Satoshi Takahashi; Shin-Ichi Yokota
  mBio, 11, 6, 2020年12月22日, ［国際誌］
  英語, 研究論文（学術雑誌）, Amikacin and colistin are effective against carbapenem-resistant Klebsiella pneumoniae In 2017, we successively isolated three carbapenem-resistant K. pneumoniae isolates (ST967) from a patient with chronic renal failure in Japan. The first (SMKP01, sputum, day 0) and second (SMKP02, blood, day 14) strains were resistant to most antimicrobials tested but still susceptible to amikacin (MICs of 4 and 0.5 mg/liter, respectively) and colistin (MIC of 0.5 mg/liter for both). The third strain (SMKP03, blood, day 51) was not susceptible to amikacin (MIC, 32 mg/liter), and its MIC for colistin varied (0.5 to 8 mg/liter). Whole-genome sequencing of SMKP01 revealed that 17 of 20 antimicrobial resistance genes, including qnrB91 (a novel qnrB2 variant) and aac(6')-Ib-cr, were located on an 86.9-kb IncFII-IncQ plasmid. The qnrB91 conferred greater fluoroquinolone resistance than qnrB2 SMKP03 aac(6')-Ib-cr that possessed a gene mutation that resulted in an R102W substitution, namely, aac(6')-Ib-D179Y, made a greater contribution to amikacin resistance than did aac(6')-Ib-cr SMKP03 harbored a nonsense mutation in mutS, which encodes a DNA repair enzyme. Introduction of this mutation into SMKP01 (SMKP01mutS A307T) resulted in a dramatic increase (>58-fold) in the frequency of spontaneous amikacin-resistant mutants relative to SMKP01, and the substantial mutants possessed aac(6')-Ib-D179Y SMKP01mutS A307T exhibited an unstable MIC for colistin (0.5 to 8 mg/liter). The results demonstrate that a disruptive mutation in MutS, arising during the clinical course of an infection, created a platform for the acquisition of amikacin nonsusceptibility and colistin heteroresistance in multidrug-resistant K. pneumoniae, mediated by the elevated frequency of spontaneous mutations.IMPORTANCE The emergence of multidrug resistance in pathogens such as Klebsiella pneumoniae is of great clinical concern. Antimicrobial resistance sometimes arises during the course of an infection. Although many studies have reported the emergence of antimicrobial resistance and novel antimicrobial resistance genes in the clinical isolates, the identity of the bacterial factor(s) that generate this emergence is still unclear. We report that a disruptive mutation in MutS, arising during the clinical course of an infection, created a context for the acquisition of colistin resistance and the emergence of a novel variant of the amikacin resistance gene in multidrug-resistant K. pneumoniae via an increase in the frequency of spontaneous mutation. This observation is important for understanding how K. pneumoniae develops multidrug resistance during infection and could potentially lead to new antimicrobial treatments for high-risk pathological microbes.
• Enhanced Immunotherapeutic Efficacy of Anti-PD-L1 Antibody in Combination with an EP4 Antagonist.
  Yamato Sajiki; Satoru Konnai; Zimeng Cai; Kensuke Takada; Tomohiro Okagawa; Naoya Maekawa; Sotaro Fujisawa; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  ImmunoHorizons, 4, 12, 837, 850, 2020年12月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, Combination treatment approaches are increasingly considered to overcome resistance to immunotherapy targeting immunoinhibitory molecules such as programmed death (PD)-1 and PD-ligand 1 (PD-L1). Previous studies have demonstrated that the therapeutic efficacy of anti-PD-L1 Abs is enhanced by combination treatment with cyclooxygenase-2 inhibitors, through downregulation of the immunosuppressive eicosanoid PGE2, although the underlying mechanism remains unclear. In this study, we show that serum PGE2 levels are upregulated after anti-PD-L1 Ab administration in a bovine model of immunotherapy and that PGE2 directly inhibits T cell activation via its receptor E prostanoid (EP) 4. Additionally, anti-PD-L1 Ab induces TNF-α production and TNF-α blockade reduces PGE2 production in the presence of anti-PD-L1 Ab, suggesting that anti-PD-L1 Ab-induced TNF-α impairs T cell activation by PGE2 upregulation. Our studies examining the therapeutic potential of the dual blockade of PD-L1 and EP4 in bovine and murine immune cells reveal that the dual blockade of PD-L1 and EP4 significantly enhances Th1 cytokine production in vitro. Finally, we show that the dual blockade decreases tumor volume and prolongs survival in mice inoculated with the murine lymphoma cell line EG7. Altogether, these results suggest that TNF-α induced by anti-PD-L1 Ab treatment is associated with T cell dysfunction via PGE2/EP4 pathway and that the dual blockade of PD-L1 and EP4 should be considered as a novel immunotherapy for cancer.
• Sitafloxacin has a potent activity for eradication of extended spectrum β-lactamase-producing fluoroquinolone-resistant Escherichia coli forming intracellular bacterial communities in uroepithelial cells.
  Yoshiki Hiyama; Toyotaka Sato; Satoshi Takahashi; Soh Yamamoto; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota; Naoya Masumori
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26, 12, 1272, 1277, 2020年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum β-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated. METHODS: To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined. RESULTS: FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections. CONCLUSIONS: The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures.
• Molecular analysis of streptomycin-resistance associating genes in Mycobacterium tuberculosis isolates from Nepal.
  Dipti Shrestha; Bhagwan Maharjan; Nan Aye Thida Oo; Norikazu Isoda; Chie Nakajima; Yasuhiko Suzuki
  Tuberculosis (Edinburgh, Scotland), 125, 101985, 101985, 2020年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, Mutation in rpsL (encoding ribosomal protein S12), rrs (encoding 16S ribosomal RNA) and gidB (encoding 7-methylguanosine methyltransferase) are associated with resistance to streptomycin (STR), which is used for the treatment of multi-drug resistant tuberculosis (MDR-TB) in Nepal. The aim of our study is to analyze the correlation between mutations in the target genes and STR-resistance in 197 Mycobacterium tuberculosis (MTB) isolates from Nepal. Mutations in rpsL was harbored by 65.9% of isolates, in which the most common mutation in rpsL is caused by K43R (58.8%) and were significantly associated with Beijing genotype (P < 0.001). About 13.2% of isolates harbored mutations in two highly mutable regions of rrs, the 530 loop and the 912 region. About 13.2% of gidB mutants do not show any mutation in rpsL and rrs, which might suggest the role of gidB mutations in STR-resistance in MTB. In addition, 5.6% of isolates do not show any mutations in three genes examined, suggesting the involvement of other mechanism in STR-resistance in MTB. Our findings can be implemented for the establishment of molecular STR-susceptibility testing, in which tuberculosis can be treated with appropriate drugs and can improve control strategies for DR-TB.
• Interaction of the plasmid-encoded quinolone resistance protein QnrB19 with Salmonella Typhimurium DNA gyrase.
  Ruttana Pachanon; Kentaro Koide; Siriporn Kongsoi; Chie Nakajima; Thoko Flav Kapalamula; Orasa Suthienkul; Yasuhiko Suzuki
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26, 11, 1139, 1145, 2020年11月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Plasmid-encoded quinolone resistance protein Qnr is an important factor in bacterial resistance to quinolones. Qnr interacts with DNA gyrase and reduces susceptibility to quinolones. The gene qnr likely spreads rapidly among Enterobacteriaceae via horizontal gene transfer. Though the vast amounts of epidemiological data are available, molecular details of the contribution of QnrB19, the predominant Qnr in Salmonella spp., to the acquisition of quinolone resistance has not yet been understood well. OBJECTIVE: We aimed to examine the role of QnrB19 in quinolone resistance acquisition using recombinant Salmonella Typhimurium DNA gyrases and QnrB19. MATERIALS AND METHODS: Recombinant QnrB19 was expressed in E. coli and purified by Ni-NTA agarose column chromatography. DNA supercoiling activities of recombinant Salmonella Typhimurium DNA gyrase were assessed with or without QnrB19 under the existence of three quinolones to measure IC50s, the concentration of each quinolone required for 50% inhibition in vitro. RESULTS: The IC50s of norfloxacin, ciprofloxacin and nalidixic acid against DNA gyrases were measured to be 0.30, 0.16 and 17.7 μg/mL, respectively. The addition of QnrB19 increased the IC50s of norfloxacin and ciprofloxacin to be 0.81 and 0.48 μg/mL, respectively, where no effect of QnrB19 was observed on the IC50 of nalidixic acid. CONCLUSION: QnrB19 was shown for the first time in vitro to have ability to grant non-classical quinolone resistance to S. Typhimurium DNA gyrase. Structural insight on quinolones in this study may contribute to investigate drugs useful for preventing the spread of plasmid carrying PMQR along with other factors associating with antimicrobial resistance in S. Typhimurium and other bacteria.
• Rapid detection of rifampicin-resistant Mycobacterium tuberculosis, based on isothermal DNA amplification and DNA chromatography.
  Yutaka Takarada; Takuya Kodera; Kumi Kobayashi; Chie Nakajima; Mitsuo Kawase; Yasuhiko Suzuki
  Journal of microbiological methods, 177, 106062, 106062, 2020年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, Rapid and easy detection of nucleotide point mutations in bacterial pathogens associated with drug resistance is essential for the proper use of antimicrobials. Here, we developed a rapid and simple method for the detection of mutations using Loop-mediated isothermal amplification (LAMP) combined with the single-tag hybridization (STH) chromatographic printed array strips (PAS) method. This procedure is able to detect four mutations (C1349 T, A1295C, G1303 T, A1304 T) in Rifampicin Resistance Determining Region (RRDR) of rifampicin-resistant Mycobacterium tuberculosis (RR-TB), simultaneously. LAMP reactions contained a LAMP primer and eight allele-specific primers for each mutation. The allele-specific primers products were detected by nucleic acid chromatography using PAS. Four detection lines were detected there, one of which was detected at different positions depend on the wild type and the mutant type. We carried out the four mutations detection using 31 genomic DNA (2 A1295T, 1 G1303 T, 6 A1304 T, 22 C1349 T) from clinical isolate. The mutations have been confirmed by sequence analysis. The detection results were completely consistent with the sequence analysis. In the present study, four mutations could be detected, but only 60% of RR-TB could be detected with these four. It is expected that the detection rate will increase by adding more mutant primers. The combined LAMP and STH chromatographic PAS method is a simple and rapid method for detecting point mutations in clinical isolates as a point-of-care testing (POCT) technique. In addition, it does not require special equipment and can meet the demand in areas where drug-resistant bacteria are endemic, such as developing countries.
• Elucidating the Structural Requirement of Uridylpeptide Antibiotics for Antibacterial Activity.
  Yuma Terasawa; Chisato Sataka; Toyotaka Sato; Kazuki Yamamoto; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Akira Katsuyama; Takanori Matsumaru; Fumika Yakushiji; Shin-Ichi Yokota; Satoshi Ichikawa
  Journal of medicinal chemistry, 63, 17, 9803, 9827, 2020年09月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, The synthesis and biological evaluation of analogues of uridylpeptide antibiotics were described, and the molecular interaction between the 3'-hydroxy analogue of mureidomycin A (3'-hydroxymureidomycin A) and its target enzyme, phospho-MurNAc-pentapeptide transferase (MraY), was analyzed in detail. The structure-activity relationship (SAR) involving MraY inhibition suggests that the side chain at the urea-dipeptide moiety does not affect the MraY inhibition. However, the anti-Pseudomonas aeruginosa activity is in great contrast and the urea-dipeptide motif is a key contributor. It is also suggested that the nucleoside peptide permease NppA1A2BCD is responsible for the transport of 3'-hydroxymureidomycin A into the cytoplasm. A systematic SAR analysis of the urea-dipeptide moiety of 3'-hydroxymureidomycin A was further conducted and the antibacterial activity was determined. This study provides a guide for the rational design of analogues based on uridylpeptide antibiotics.
• Emergence of vancomycin- and teicoplanin-resistant Enterococcus faecium via vanD5-harbouring large genomic island.
  Toyotaka Sato; Takayuki Wada; Masaaki Shinagawa; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Satoshi Takahashi; Shin-Ichi Yokota
  The Journal of antimicrobial chemotherapy, 75, 9, 2411, 2415, 2020年06月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Treatment of VRE is of clinical concern. While certain numbers of vanD-type VRE have been isolated, only two vanD5-harbouring Enterococcus faecium isolates have been reported in Canada and Japan. METHODS: We report the isolation of vanD5-type E. faecium and the first ever determination of the whole-genome sequence to investigate the possible mechanisms of the acquisition of the vanD5 gene cluster in E. faecium. RESULTS: Two vanD5-harbouring vancomycin-resistant E. faecium were isolated from the skin (SMVRE19) and faeces (SMVRE20) of a patient with a skin ulcer in Japan. The isolates exhibited vancomycin and teicoplanin MIC values of 128 mg/L, whilst the previous isolates of vanD5-harbouring E. faecium were only resistant to vancomycin. SMVRE19 and SMVRE20 were clones related to ST18, which is also seen in vanA- and vanB-type VRE. These isolates harboured an insertion element, ISEfm1, in the ddl gene, similar to a previously described teicoplanin-resistant vanD3-type E. faecium. The vanD5 gene cluster was integrated into the SMVRE20 chromosome as a part of a large genomic island (approximately 127 kb), similar to other recently spreading vanD variants in the Netherlands. The genomic island shared the greatest similarity with a part of the Blautia coccoides genome sequence, except for the region surrounding the vanD gene cluster. CONCLUSIONS: This study reports that emergence of vancomycin- and teicoplanin-resistant vanD5-type E. faecium occurred via acquisition of the vanD5 cluster and ISEfm1 insertion into ddl. Considering the genetic similarity between the various VRE strains, the current study should serve as a warning against the spread of vanD5-type VRE.
• WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae.
  Jong-Hoon Park; Tomoyuki Yamaguchi; Yuki Ouchi; Kentaro Koide; Shigetarou Mori; Hyun Kim; Tetsu Mukai; Chie Nakajima; Yasuhiko Suzuki
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26, 4, 335, 342, 2020年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Mycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico. Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. CONCLUSIONS/SIGNIFICANCE: The inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens.
• Campylobacter upsaliensis isolated from a giant hepatic cyst.
  Yasuo Ohkoshi; Toyotaka Sato; Hiromi Murabayashi; Kohei Sakai; Yasunari Takakuwa; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26, 7, 752, 755, 2020年03月18日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Campylobacter upsaliensis is an enteropathogenic bacterium in animals, and is also rarely isolated from humans, where it can cause enteritis and bacteremia. This report describes the first case of isolation of C. upsaliensis from an infected giant hepatic cyst. This bacterium could not be cultured from abscess punctuate in a usual Campylobacter-selection medium (charcoal cefoperazone deoxycholate agar medium), because of high concentration of cefoperazone as a selection agent. It could not identified by matrix-assisted laser desorption ionization-time of flight mass spectrum. Rather, it was identified as C. upsaliensis by whole genome sequencing, including by multilocus sequence typing.
• Mutations of rpoB, katG and inhA genes in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia.
  Eddie S Solo; Chie Nakajima; Trevor Kaile; Precious Bwalya; Grace Mbulo; Yukari Fukushima; Sylvia Chila; Nanthan Kapata; Yogendra Shah; Yasuhiko Suzuki
  Journal of global antimicrobial resistance, 22, 302, 307, 2020年03月10日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: It is established that resistance to rifampicin (RIF) in 90% of the RIF resistantM. tuberculosis strains is attributable to point mutations in the rpoB gene while 50-95% of M. tuberculosis resistance to isoniazid (INH) is caused by mutations in katG gene. However, the patterns and frequencies of mutations vary with geographical differences. In Zambia, the genetic resistance of M. tuberculosis to RIF and INH were unreported before this study. METHODS: Using sequencing, we analyzed rpoB, katG and inhA genes for 99 multidrug-resistant (MDR) and 49 pan-susceptible M. tuberculosis isolates stored at a tuberculosis reference laboratory from 2013 to 2016 and compared with published profiles from other African countries. RESULTS: Ninety six percent (95/99) of the MDR-TB isolates carried mutations in bothrpoB and katG genes. No mutations were detected among the pan-susceptible isolates. rpoB gene codon 531 and katG gene codon 315 at 55.6 % (55/99) and 94.9 % (94/99) were the most altered among the RIF and INH resistant isolates, respectively. Distinctly, katG mutations were predominantly high among Zambian isolates (96%) compared to other countries in the region. CONCLUSION: The drug resistant associated mutations to RIF and INH circulating in Zambia are similar to what have been reported globally, therefore our data validates the applicability of molecular diagnostic tools in Zambia. However,katG mutations were predominantly high among M. tuberculosis isolates in this study compared to other regional countries and might disassociate cross-boundary transmission of MDR-TB from other African nations.
• Comparison of Loop-Mediated Isothermal Amplification, Microscopy, Culture, and PCR for Diagnosis of Pulmonary Tuberculosis.
  Benjawan Phetsuksiri; Janisara Rudeeaneksin; Sopa Srisungngam; Supranee Bunchoo; Wiphat Klayut; Chie Nakajima; Shigeyuki Hamada; Yasuhiko Suzuki
  Japanese journal of infectious diseases, 73, 4, 272, 277, 2020年02月28日, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Diagnosis tuberculosis (TB) in endemic countries is challenging due to high caseloads and limited resources. A simple, cost-effective diagnostic test for rapid detection of Mycobacterium tuberculosis in clinical specimens is in need. In Thailand, we evaluated the performance of in-house loop-mediated isothermal amplification (LAMP) targeting M. tuberculosis 16s rRNA gene for TB diagnosis. A total of 252 sputum samples from pulmonary TB suspects were analyzed. The sensitivity of LAMP was 99.04% (103/104; 95% confidential interval [CI]: 94.76-99.98%) and 72.73% (16/22; 95% CI: 49.78-89.27) for smear-positive and smear-negative samples with TB-culture positivity, respectively. LAMP detected 20.69% (24/116) of TB-culture negative samples but those all were positive by conventional PCR. The sensitivity of LAMP was higher than that of sputum microscopy while the performance of LAMP was similar to PCR. None of the samples positive for non-tuberculous mycobacteria by culture and PCR was positive by LAMP. Compared with TB culture, the positive predictive value (PPV), negative predictive value (NPV) and kappa coefficient of LAMP were 83.22%, 88.33% and 0.75 respectively. Based on the diagnostic performance, we proposed that this LAMP would be suitable as a potential diagnostic test for rapid TB diagnosis in resource-limited laboratory settings.
• Contribution of β-lactamase and efflux pump overproduction to tazobactam-piperacillin resistance in clinical isolates of Escherichia coli.
  Yuuki Suzuki; Toyotaka Sato; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Satoshi Takahashi; Shin-Ichi Yokota
  International journal of antimicrobial agents, 55, 4, 105919, 105919, 2020年02月13日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Tazobactam-piperacillin (TZP) is a mixture of a broad-spectrum penicillin and an irreversible β-lactamase inhibitor. TZP is effective against Gram-negative bacteria that produce extended-spectrum β-lactamases, and it is used as a first-line or second-line drug to treat serious infections. METHODS: This study identified three TZP-resistant and two TZP-intermediate strains among 514 clinical isolates of Escherichia coli. RESULTS: These five isolates possessed one or more β-lactamase genes, blaTEM-1, blaCTX-M-2, blaCTX-M-14, and/or blaCMY-8. The expression levels of β-lactamase genes and acrAB genes in the strains were examined by using real-time reverse transcription PCR. The total enzymatic piperacillin-degrading activity in cells was determined. Two TZP-resistance mechanisms were identified: hyperproduction of TEM-1 in the two resistant strains; and simultaneous high production of β-lactamase and efflux pump AcrAB in the two TZP-intermediate isolates. The latter are an international high-risk clone O25b:H4-ST131-H30R. CONCLUSION: TZP resistance is still rare in clinical isolates of E. coli. However, resistance can develop on high production and/or combinations of known antimicrobial resistance mechanisms in different ways.
• In Vitro Derivation of Fluoroquinolone-Resistant Mutants from Multiple Lineages of Haemophilus influenzae and Identification of Mutations Associated with Fluoroquinolone Resistance.
  Hiroyuki Honda; Toyotaka Sato; Masaaki Shinagawa; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Koji Kuronuma; Satoshi Takahashi; Hiroki Takahashi; Shin-Ichi Yokota
  Antimicrobial agents and chemotherapy, 64, 2, 2020年01月27日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Haemophilus influenzae is a pathogenic bacterium that causes respiratory and otolaryngological infections. The increasing prevalence of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) is a clinical concern. Fluoroquinolones are alternative agents to β-lactams. However, the emergence and increasing prevalence of fluoroquinolone-resistant H. influenzae have been reported. The current risk of fluoroquinolone resistance in H. influenzae (especially in high-BLNAR) has not yet been evaluated. Here, we examined the development of fluoroquinolone resistance in fluoroquinolone-susceptible clinical H. influenzae isolates in vitro during passaging in the presence of moxifloxacin (from 0.03 to 128 mg/liter). Twenty-nine isolates were examined. Seventeen isolates (58.6%) showed reduced moxifloxacin susceptibility, and 10 of these 17 isolates (34.5% of all isolates) exceeded the Clinical and Laboratory Standards Institute breakpoint for moxifloxacin (MIC of >1 mg/liter) after repeat cultivation on moxifloxacin-containing agar. Seven of these ten isolates were high-BLNAR and represented multiple lineages. We identified 56 novel mutations in 45 genes induced during the development of fluoroquinolone resistance, except the defined quinolone resistance-determining regions (Ser84Leu and Asp88Tyr/Gly/Asn in GyrA and Gly82Asp, Ser84Arg, and Glu88Lys in ParC). Glu153Leu and ΔGlu606 in GyrA, Ser467Tyr and Glu469Asp in GyrB, and ompP2 mutations were novel mutations contributing to fluoroquinolone resistance in H. influenzae In conclusion, H. influenzae clinical isolates from multiple lineages can acquire fluoroquinolone resistance by multiple novel mutations. The higher rate of derivation of fluoroquinolone-resistant H. influenzae from high-BLNAR than β-lactamase-negative ampicillin-susceptible isolates (P = 0.01) raises the possibility of the emergence and spread of fluoroquinolone-resistant high-BLNAR in the clinical setting.
• タイ国のブタとブタ肉から分離されたMRSAの分子的特性と抗菌薬耐性(Molecular characterization and antimicrobial resistance of MRSA from pigs and pork in Thailand)
  Tanomsridachchai Wimonrat; 中島 千絵; Changkaew Kanjana; Changkwanyeun Ruchirada; Prapasawat Watsawan; Intarapuk Apiradee; Yamasamit Nattapong; Suthienkul Orasa; 鈴木 定彦
  日本細菌学雑誌, 75, 1, 60, 60, 日本細菌学会, 2020年01月
  英語
• フィリピンの食用動物から分離されたE.coliのキノロン耐性決定因子の検出(Detection of quinolone resistance determinants in E. coli from food animals in the Philippines)
  Belotindos Lawrence; Mingala Claro; Villanueva Marvin; 中島 千絵; 鈴木 定彦
  日本細菌学雑誌, 75, 1, 64, 64, 日本細菌学会, 2020年01月
  英語
• 病原性抗酸菌における細胞外DNAの存在と抗酸菌の生理におけるその役割(Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology)
  イリノフ・アレクサンドル; シャバン・アミナ; 袴田 真理子; 西山 晃史; 尾関 百合子; 福島 由華里; 中島 千絵; 立石 善隆; 鈴木 定彦; 松本 壮吉
  日本細菌学雑誌, 75, 1, 74, 74, 日本細菌学会, 2020年01月
  英語
• 水平ゲノム転移を介したvanD5バンコマイシン耐性遺伝子を保有するEnterococcus faeciumの出現(Emergence of vanD5-type vancomycin-resistant Enterococcus faecium via horizontal genomic transfer)
  佐藤 豊孝; 和田 崇之; 福島 由華里; 中島 千絵; 鈴木 定彦; 高橋 聡; 横田 伸一
  日本細菌学雑誌, 75, 1, 100, 100, 日本細菌学会, 2020年01月
  英語
• The performance of an in-house loop-mediated isothermal amplification for the rapid detection of Mycobacterium tuberculosis in sputum samples in comparison with Xpert MTB/RIF, microscopy and culture.
  Benjawan Phetsuksiri; Wiphat Klayut; Janisara Rudeeaneksin; Sopa Srisungngam; Supranee Bunchoo; Sarawut Toonkomdang; Thanee Wongchai; Chie Nakajima; Yasuhiko Suzuki
  Revista do Instituto de Medicina Tropical de Sao Paulo, 62, e36, 2020年, ［国際誌］
  英語, 研究論文（学術雑誌）, Simple, low-cost and effective diagnostic tests for tuberculosis (TB) are needed especially in TB-high burden settings. The present study evaluated the performance of an in-house loop-mediated isothermal amplification (LAMP) for diagnosing TB by comparing it to Xpert MTB/RIF, microscopy and culture. In Thailand, a total of 204 excess sputum samples volume after the processing of cultures were used for Mycobacterium tuberculosis (MTB) detection by Xpert MTB/RIF and LAMP. Based on culture results as the gold standard, the overall sensitivity of LAMP and Xpert MTB/RIF were 82.1% (126/153; 95% confidential interval [CI]: 75.4-88.98%) and 86.9 % (133/153; 95% CI: 80.5-90.8%) respectively, and the specificity of both tests was 100% (51/51; 95% CI: 93.0-100.0%). In comparison with Xpert MTB/RIF, the sensitivity and specificity of LAMP were 94.7% (126/133; 95% CI: 89.5-97.9%), and 100.0% (73/73; 95% CI: 94.9-100.0%), respectively. The average threshold cycle (Ct) of Xpert MTB/RIF detection for positive and negative LAMP results was statistically different, of 18.4 and 27.0, respectively (p < 0.05). In comparison with the acid-fast staining technique, and analyzing LAMP and Xpert MTB/RIF in smear-negative/culture-positive specimens, there was an increase of the detection rate by 47.7% (21/44) and 54.6% (24/44). The diagnostic sensitivity and specificity of LAMP appeared to be comparable to those of Xpert MTB/RIF. We claim that this LAMP has potential to provide a sensitive diagnostic test for the rapid TB diagnosis. It allowed a fast detection of MTB before the cultures and it could be used in resource-limited laboratory settings.
• Mesalazine-induced lung injury with severe respiratory failure successfully treated with steroids and non-invasive positive pressure ventilation.
  Hajime Oi; Atsushi Suzuki; Yasuhiko Yamano; Toshiki Yokoyama; Toshiaki Matsuda; Kensuke Kataoka; Yasuhiko Suzuki; Tomoki Kimura; Yasuhiro Kondoh
  Respiratory medicine case reports, 31, 101157, 101157, 2020年, ［国際誌］
  英語, Drug-induced lung injury (DLI) has become more common because of the increasing number of therapeutic agents in use. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is one of the key drugs for the treatment of ulcerative colitis (UC). Although mesalazine-induced lung injury has been previously reported, few cases have included severe respiratory failure. In this report, we present a case of mesalazine-induced lung injury with severe respiratory failure, which was improved by discontinuation of mesalazine and introduction of corticosteroid therapy and ventilation support with non-invasive positive pressure ventilation (NPPV). We also review the previous literature on mesalazine-induced lung injury.
• PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade.
  Otgontuya Ganbaatar; Satoru Konnai; Tomohiro Okagawa; Yutaro Nojima; Naoya Maekawa; Erina Minato; Atsushi Kobayashi; Ryo Ando; Nobuya Sasaki; Daisuke Miyakoshi; Osamu Ichii; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  PloS one, 15, 11, e0234218, 2020年, ［国際誌］
  英語, 研究論文（学術雑誌）, Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy in cattle and dogs. However, the immunological role of the PD-1/PD-L1 pathway for chronic equine diseases, including tumors, remains unclear. In this study, we identified cDNA sequences of equine PD-1 (EqPD-1) and PD-L1 (EqPD-L1) and investigated the role of anti-bovine PD-L1 mAbs against EqPD-L1 using in vitro assays. In addition, we evaluated the expression of PD-L1 in tumor tissues of equine malignant melanoma (EMM). The amino acid sequences of EqPD-1 and EqPD-L1 share a considerable identity and similarity with homologs from non-primate species. Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1 in flow cytometry, and one of these cross-reactive mAbs blocked the binding of equine PD-1/PD-L1. Of note, immunohistochemistry confirmed the PD-L1 expression in EMM tumor tissues. A cultivation assay revealed that PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells. These findings showed that our anti-PD-L1 mAbs would be useful for analyzing the equine PD-1/PD-L1 pathway. Further research is warranted to discover the immunological role of PD-1/PD-L1 in chronic equine diseases and elucidate a future application in immunotherapy for horses.
• Properties of biopolymers detection with piezoelectric polymer biosensor in relaxation behavior process
  Mariko Takeda; Kouki Yahagi; Takamichi Hirata; Takashi Kuroiwa; Chie Nakajima; Yasuhiko Suzuki; Fumio Munakata
  IEEJ Transactions on Sensors and Micromachines, 140, 2, 43, 49, 2020年, ［査読有り］
  研究論文（学術雑誌）
• WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis.
  Yuki Ouchi; Tetsu Mukai; Kentaro Koide; Tomoyuki Yamaguchi; Jong-Hoon Park; Hyun Kim; Kazumasa Yokoyama; Aki Tamaru; Stephen V Gordon; Chie Nakajima; Yasuhiko Suzuki
  Tuberculosis (Edinburgh, Scotland), 120, 101891, 101891, 2020年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro antimycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette-Guérin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains.
• Upregulation of PD-L1 expression by prostaglandin E2 and the enhancement of IFN-γ by anti-PD-L1 antibody combined with a COX-2 inhibitor in Mycoplasma bovis infection
  Goto S; Konnai S; Hirano Y; Kohara J; Okagawa T; Maekawa N; Sajiki Y; Watari K; Minato E; Kobayashi A; Gondaira S; Higuchi H; Koiwa M; Tajima M; Taguchi E; Uemura R; Yamada S; Kaneko M; Kato Y; Yamamoto K; Toda M; Suzuki Y; Murata S; Ohashi K
  Front Vet Sci, 7, 12, 12, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine mycoplasmosis caused by Mycoplasma bovis results in pneumonia and mastitis in cattle. We previously demonstrated that the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E2 (PGE2) suppressed immune responses and upregulated PD-L1 expression in Johne's disease, a bacterial infection in cattle. In this study, we investigated the role of PGE2 in immune dysfunction and the relationship between PGE2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE2 and PD-L1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE2 levels were positively correlated with the proportions of PD-L1+ monocytes in M. bovis-infected cattle. Additionally, plasma PGE2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE2 could be one of the inducers of PD-L1 expression and could be involved in immunosuppression during M. bovis infection. In vitro blockade assays using anti-bovine PD-L1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE2 and the PD-1/PD-L1 pathway.
• Clinical efficacy of the combined treatment of anti-PD-L1 rat-bovine chimeric antibody with a COX-2 inhibitor in calves infected with Mycoplasma bovis
  Goto S; Konnai S; Hirano Y; Kohara J; Okagawa T; Maekawa N; Sajiki Y; Watari K; Minato E; Kobayashi A; Gondaira S; Higuchi H; Koiwa M; Tajima M; Taguchi E; Ishida M; Uemura R; Yamada S; Kaneko M; Kato Y; Yamamoto K; Toda M; Suzuki Y; Murata S; Ohashi K
  Jpn J Vet Res, 68, 2, 77, 90, 2020年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Acquisition of fluoroquinolone resistance leads to increased biofilm formation and pathogenicity in Campylobacter jejuni.
  Matthew V X Whelan; Laura Ardill; Kentaro Koide; Chie Nakajima; Yasuhiko Suzuki; Jeremy C Simpson; Tadhg Ó Cróinín
  Scientific reports, 9, 1, 18216, 18216, 2019年12月03日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The World Health Organization has listed C. jejuni as one of 12 microorganisms on a global priority list for antibiotic resistance due to a rapid increase in strains resistant to fluoroquinolone antibiotics. This fluoroquinolone resistance is conferred through a single point mutation in the QRDR region within the gyrA gene known to be involved in DNA supercoiling. We have previously revealed that changes in DNA supercoilikng play a major role in the regulation of virulence in C. jejuni with relaxation of DNA supercoiling associated with increased attachment to and invasion of human epithelial cells. The aim of this study was to investigate whether fluoroquinolone resistant strains of C. jejuni displayed altered supercoiling associated phenotypes. A panel of fluoroquinolone resistant mutants were derived and shown to have a greater ability to form viable biofilms under aerobic conditions, invade epithelial cells and promote virulence in the Galleria mellonella model of infection. We thus report for the first time that fluoroquinolone resistance in C. jejuni is associated with an increase in virulence and the ability to form viable biofilms in oxygen rich environments. These altered phenotypes likely play a critical role in the continued increase in fluoroquinolone resistance observed for this important pathogen.
• WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium.
  Koide K; Kongsoi S; Nakajima C; Suzuki Y
  Bioscience, biotechnology, and biochemistry, 83, 12, 2249, 2256, 2019年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The inhibitory effect of WQ-3810 on DNA gyrase was assayed to evaluate the potential of WQ-3810 as a candidate drug for the treatment of quinolone resistant Salmonella Typhymurium infection. The inhibitory effect of WQ-3810, ciprofloxacin and nalidixic acid was compared by accessing the drug concentration that halves the enzyme activity (IC50) of purified S. Typhimurium wildtype and mutant DNA gyrase with amino acid substitution at position 83 or/and 87 in subunit A (GyrA) causing quinolone resistance. As a result, WQ-3810 reduced the enzyme activity of both wildtype and mutant DNA gyrase at a lower concentration than ciprofloxacin and nalidixic acid. Remarkably, WQ-3810 showed a higher inhibitory effect on DNA gyrase with amino acid substitutions at position 87 than with that at position 83 in GyrA. This study revealed that WQ-3810 could be an effective therapeutic agent, especially against quinolone resistant Salmonella enterica having amino acid substitution at position 87.
• Pyrimidine Analogues as a New Class of Gram-Positive Antibiotics, Mainly Targeting Thymineless-Death Related Proteins.
  Oe C; Hayashi H; Hirata K; Kawaji K; Hashima F; Sasano M; Furuichi M; Usui E; Katsumi M; Suzuki Y; Nakajima C; Kaku M; Kodama EN
  ACS infectious diseases, 6, 6, 1490, 1500, 2019年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Multidrug-resistant (MDR) bacteria are widespread throughout the world and pose an increasingly serious threat to human and animal health. Besides implementing strict measures to prevent improper antibiotic use, it remains essential that novel antibiotics must be developed. These antibiotics need to exert their activity via mechanisms different from those employed by currently approved antibiotics. In this study, we used several 5-fluorouracil (5-FU) analogues as chemical probes and investigated the potential of these pyrimidine analogues as antibacterial agents. Several 5-FU derivatives exerted potent activity against strains of Gram-positive cocci (GPC) that are susceptible or resistant toward approved antibiotics, without showing cross-resistance. Furthermore, we have provided evidence that the pyrimidine analogues exerted anti-GPC activity via thymineless death by inhibition of thymidylate synthetase (ThyA) and/or inhibition of RNA synthesis. Interestingly, whole genome resequencing of in vitro-selected, pyrimidine analogue-resistant Staphylococcus aureus mutants indicated that S. aureus strains with pyrimidine-analogue resistance induced an amino acid (AA) substitution, deletion, and/or insertion into thymineless-death related proteins except for ThyA, or enhanced the ThyA transcription level. Thus, S. aureus may avoid altering the ThyA function by introducing an AA substitution, suggesting that the pyrimidine analogues, which directly bind to ThyA without phosphorylation, may be more effective and show a higher genetic barrier than the pyrimidines that depend on phosphorylation for activity. The findings of this study may assist in the future development of a novel class of antibiotics for combating MDR GPC, including methicillin-resistant S. aureus and vancomycin-resistant Enterococci.
• Insight into genetic diversity of Mycobacterium tuberculosis in Kandy, Sri Lanka reveals predominance of the Euro-American lineage.
  Mendis C; Thevanesam V; Kumara A; Wickramasinghe S; Madegedara D; Gamage C; Gordon SV; Suzuki Y; Ratnatunga C; Nakajima C
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 87, 84, 91, 2019年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Sri Lanka is a country where the molecular epidemiology of Mycobacterium tuberculosis (MTB) is poorly explored. Therefore, this study was performed to identify circulating lineages/sub-lineages of MTB and their transmission patterns. METHODS: DNA was extracted from 89 isolates of MTB collected during 2012 and 2013 from new pulmonary tuberculosis patients in Kandy, Sri Lanka and analyzed by spoligotyping, large sequence polymorphism (LSP), mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing, and drug resistance-associated gene sequencing. RESULTS: The predominant lineage was lineage 4 (Euro-American, 45.9%), followed by lineage 1 (Indo-Oceanic, 29.4%), lineage 2 (East-Asian, 23.5%), and lineage 3 (Central-Asian, 1.2%). Among 26 spoligotype patterns, eight were undesignated or new types and seven of these belonged to lineage 4. Undesignated lineage 4/SIT124 (n=2/8) and SIT3234 (n=8/8) clustered together based on 24-locus MIRU-VNTR typing. The dominant sub-lineage was Beijing/SIT1 (n=19), with the isoniazid resistance katG G944C mutation (Ser315Thr) detected in two of them. CONCLUSIONS: The population structure of MTB in Kandy, Sri Lanka was different from that in the South Asian region. The clonal expansion of locally evolved lineage 4/SIT3234 and detection of the pre-multidrug resistant Beijing isolates from new tuberculosis patients is alarming and will require continuous monitoring.
• Immune inhibitory function of bovine CTLA-4 and the effects of its blockade in IFN-γ production
  Watari K; Konnai S; Maekawa N; Okagawa T; Suzuki Y; Murata S; Ohashi K
  BMC Vet Res, 15, 1, 380, 380, 2019年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is known as an immune inhibitory receptor that is expressed on activated effector T cells and regulatory T cells. When CTLA-4 binds to CD80 or CD86, immunoinhibitory signals are transmitted to retain a homeostasis of the immune response. Recent studies have reported that CTLA-4 is upregulated in chronic infections and malignant neoplasms, contributing to host immune dysfunction. On the other hand, the blockade of CTLA-4 and CD80 or CD86 binding by antibody restores the immune response against these diseases. In a previous report, we indicated that the expression of CTLA-4 was closely associated with disease progression in cattle infected with the bovine leukemia virus (BLV). In this study, we established an anti-bovine CTLA-4 antibody to confirm its immune enhancing effect. RESULTS: Bovine CTLA-4-Ig binds to bovine CD80 and CD86 expressing cells. Additionally, CD80 and CD86 bind to CTLA-4 expressing cells in an expression-dependent manner. Bovine CTLA-4-Ig significantly inhibited interferon-gamma (IFN-γ) production from bovine peripheral blood mononuclear cells (PBMCs) activated by Staphylococcus enterotoxin B (SEB). An established specific monoclonal antibody (mAb) for bovine CTLA-4 specifically recognized only with bovine CTLA-4, not CD28, and the antibody blocked the binding of CTLA-4-Ig to both CD80 and CD86 in a dose-dependent manner. The bovine CTLA-4 mAb significantly restored the inhibited IFN-γ production from the CTLA-4-Ig treated PBMCs. In addition, the CTLA-4 mAb significantly enhanced IFN-γ production from CTLA-4 expressing PBMCs activated by SEB. Finally, we examined whether a CTLA-4 blockade by CTLA-4 mAb could restore the immune reaction during chronic infection; the blockade assay was performed using PBMCs from BLV-infected cattle. The CTLA-4 blockade enhanced IFN-γ production from the PBMCs in response to BLV-antigens. CONCLUSIONS: Collectively, these results suggest that anti-bovine CTLA-4 antibody can reactivate lymphocyte functions and could be applied for a new therapy against refractory chronic diseases. Further investigation is required for future clinical applications.
• Prostaglandin E2 induced immune exhaustion and enhancement of anti-viral effects by anti-PD-L1 antibody combined with COX-2 inhibitor in bovine leukemia virus infection
  Sajiki Y; Konnai S; Okagawa T; Nishimori A; Maekawa N; Goto S; Watari K; Minato E; Kobayashi A; Kohara J; Yamada S; Kato Y; Takahashi H; Terasaki N; Takeda A; Yamamoto K; Toda M; Suzuki Y; Murata S; Ohashi K
  J Immunol, 203, 5, 1313, 1324, 2019年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE2 production by PBMCs. Transcription of BLV genes was activated via PGE2 receptors EP2 and EP4, further suggesting that PGE2 contributes to disease progression. In contrast, inhibition of PGE2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.
• イヌ腫瘍組織およびイヌ腫瘍由来細胞株におけるイヌHER2の発現解析
  吉武 志江奈; 今内 覚; 前川 直也; 賀川 由美子; 西村 麻紀; 岡川 朋弘; 鈴木 定彦; 高木 哲; 中川 貴之; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 162回, 380, 380, (公社)日本獣医学会, 2019年08月
  日本語
• BLV感染症に対するCOX-2阻害剤と抗PD-L1抗体併用法の抗ウイルス効果の検討
  佐治木 大和; 今内 覚; 岡川 朋弘; 前川 直也; 後藤 伸也; 小原 潤子; 山田 慎二; 加藤 幸成; 鈴木 定彦; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 162回, 381, 381, (公社)日本獣医学会, 2019年08月
  日本語
• Mycoplasma bovis感染症に対する抗PD-L1キメラ抗体を用いた臨床試験
  後藤 伸也; 今内 覚; 平野 佑気; 小原 潤子; 岡川 朋弘; 前川 直也; 鈴木 定彦; 加藤 幸成; 村田 史郎; 大橋 和彦
  日本獣医学会学術集会講演要旨集, 162回, 381, 381, (公社)日本獣医学会, 2019年08月
  日本語
• Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations.
  Minami Ohara; Yasuhiko Suzuki; Saki Shinohara; Inna Y Gong; Crystal L Schmerk; Rommel G Tirona; Ute I Schwarz; Ming-Shien Wen; Ming Ta Michael Lee; Kiyoshi Mihara; Edith A Nutescu; Minoli A Perera; Larisa H Cavallari; Richard B Kim; Harumi Takahashi
  Clinical pharmacokinetics, 58, 8, 1077, 1089, 2019年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. METHODS: Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC50) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. RESULTS: Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p < 0.01). EC50 showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 μg/mL for Asian, White and African American patients, respectively, p < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic (CYP2C9*3,*8 and VKORC1 -1639G>A) factors, as well as African American ethnicity. In all three racial groups, genetic predictors of INR appeared to have greater influence than demographic/clinical predictors. Both CL(S) and EC50 contributed to the over-anticoagulation response to warfarin. Patients having VKORC1 -1639 G>A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4. CONCLUSIONS: Although there were contrasting racial differences in CL(S) and EC50 that impacted on the INR, the racial difference in EC50 was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.
• Erratum to "Insight into multidrug-resistant Beijing genotype Mycobacterium tuberculosis isolates in Myanmar" [Int. J. Infect. Dis. 76 (November) (2018) 109-119].
  San LL; Aye KS; Nan Aye TO; Shwe MM; Fukushima Y; Gordon SV; Suzuki Y; Nakajima C
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 85, 214, 214, 2019年08月, ［査読有り］, ［国際誌］
  英語
• DNA gyrase could be a crucial regulatory factor for growth and survival of Mycobacterium leprae.
  Hyun Kim; Yasuo Fukutomi; Chie Nakajima; Youn Uck Kim; Shigetarou Mori; Keigo Shibayama; Noboru Nakata; Yasuhiko Suzuki
  Scientific reports, 9, 1, 10815, 10815, 2019年07月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Leprosy, an important infectious disease in humans caused by Mycobacterium leprae (Mle), remains endemic in many countries. Notably, the pathogen cannot be cultured in vitro, except in mouse footpads in vivo. The molecular basis of these characteristics and the mechanisms remain unknown. Consequently, analysis of Mle growth and survival is urgently needed to develop novel therapies against leprosy, including rapid, simple, and specific methods to detect infection. Here, we demonstrated the functional role and contribution of Mle-DNA gyrase, which regulates DNA topology, DNA replication, and chromosome segregation to promote bacterial growth and survival, in Mle growth and survival in vitro and in vivo. The optimum temperature for Mle-DNA gyrase activity was 30 °C. When the DNA gyrB-gyrA genes in Mycobacterium smegmatis were replaced with the Mle gyrase genes by allelic exchange, the recombinants could not grow at 37 °C. Moreover, using radiorespirometry analysis for viability of Mle bacilli, we found that Mle growth was more vigorous at 25-30 °C than at 37 °C, but was inhibited above 40 °C. These results propose that DNA gyrase is a crucial factor for Mle growth and survival and its sensitivity to temperature may be exploited in heat-based treatment of leprosy.
• Field diagnosis and genotyping of chikungunya virus using a dried reverse transcription loop-mediated isothermal amplification (LAMP) assay and MinION sequencing.
  Hayashida K; Orba Y; Sequeira PC; Sugimoto C; Hall WW; Eshita Y; Suzuki Y; Runtuwene L; Brasil P; Calvet G; Rodrigues CDS; Santos CCD; Mares-Guia MAM; Yamagishi J; Filippis AMB; Sawa H
  PLoS neglected tropical diseases, 13, 6, e0007480, 2019年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Detection and sequencing of chikungunya virus (CHIKV) genome was performed using a combination of a modified reverse transcription loop-mediated isothermal amplification (RT-LAMP) method and a MinION sequencer. We developed the protocol for drying all the reagents for the RT-LAMP in a single reaction tube. Using this system, the CHIKV genome was effectively amplified under isothermal conditions, and used as a template for MinION sequencing with a laptop computer. Our in-house RT-LAMP method and MinION sequencing system were also validated with RNAs and serum samples from recent outbreaks of CHIKV patients in Brazil. The obtained sequence data confirmed the CHIKV outbreaks and identified the genotype. In summary, our established inexpensive on-site genome detection and sequencing system is applicable for both diagnosis of CHIKV infected patients and genotyping of the CHIKV virus in future outbreak in remote areas.
• Mixed Mycobacterium tuberculosis Lineage Infection in 2 Elephants, Nepal.
  Paudel S; Nakajima C; Mikota SK; Gairhe KP; Maharjan B; Subedi S; Poudel A; Sashika M; Shimozuru M; Suzuki Y; Tsubota T
  Emerging infectious diseases, 25, 5, 1031, 1032, 2019年05月, ［査読有り］, ［国際誌］
  英語, Tuberculosis in elephants is primarily caused by Mycobacterium tuberculosis. We identified mixed M. tuberculosis lineage infection in 2 captive elephants in Nepal by using spoligotyping and large sequence polymorphism. One elephant was infected with Indo-Oceanic and East African-Indian (CAS-Delhi) lineages; the other was infected with Indo-Oceanic and East Asian (Beijing) lineages.
• Prevalence of 16S rRNA methylases in Gram-negative bacteria derived from companion animals and livestock in Japan.
  Usui M; Kajino A; Kon M; Fukuda A; Sato T; Shirakawa T; Kawanishi M; Harada K; Nakajima C; Suzuki Y; Tamura Y
  The Journal of veterinary medical science, 81, 6, 874, 878, 2019年05月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, The emergence and spread of aminoglycoside-resistant bacteria are a public health concern. The acquisition of the genes encoding 16S rRNA methylases, such as armA, rmtA, and rmtB, confers high-level resistance to aminoglycosides. However, the prevalence has not been well investigated in Japanese veterinary fields. To determine the prevalence of 16S rRNA methylases in animals, we detected 16S rRNA methylases genes in Gram-negative bacteria from animals. Here, we report the isolation of rmtB amd armA from two of the 446 Escherichia coli (0.5%) and one of the 103 Klebsiella spp. isolates (1.0%) from companion animals, respectively. However, none of the isolations were observed from 2445 E. coli isolates derived from livestock in Japan. The prevalence of 16S rRNA methylases in animals, especially in companion animals, should be carefully monitored in Japanese veterinary fields to avoid the spreading of the genes.
• Evaluation of Susceptibilities to Carbapenems and Faropenem Against Cephalosporin-Resistant Neisseria gonorrhoeae Clinical Isolates with penA Mosaic Alleles.
  Yoshiki Hiyama; Satoshi Takahashi; Toyotaka Sato; Masaaki Shinagawa; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Naoya Masumori; Shin-Ichi Yokota
  Microbial drug resistance (Larchmont, N.Y.), 25, 3, 427, 433, 2019年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Neisseria gonorrhoeae is a principal pathogen for sexually transmitted infections, especially for male urethritis. Currently, the prevalence of multidrug resistance is increasing. Carbapenems are broad-spectrum antimicrobials that are widely used in the clinical setting, especially for multidrug-resistant Gram-negative bacteria. However, susceptibility to carbapenems has not been well evaluated for cephalosporin-resistant N. gonorrhoeae isolates. In this study, we determined the susceptibility to a series of carbapenems (meropenem, imipenem, doripenem, and biapenem) and faropenem against cephalosporin-resistant (resistant to cefixime, but susceptible to ceftriaxone) and cephalosporin-susceptible N. gonorrhoeae clinical isolates. The gene mutations associated with β-lactam resistance were evaluated. All cephalosporin-resistant N. gonorrhoeae isolates possessed mosaic mutation alleles in penA (NG-STAR penA-10.001, 27.001, or 108.001). They exhibited a low minimum inhibitory concentration (MIC) (≤0.125 mg/L) for meropenem and markedly high MICs (0.5-2 mg/L) for other carbapenems and faropenem. The strongest association was observed between the mosaic alleles in penA and decreased susceptibility to carbapenems and faropenem compared with mutations in mtrR, porB, and ponA. These results suggest that meropenem may serve as an alternative therapeutic agent for cephalosporin-resistant N. gonorrhoeae with a mosaic allele in penA, whereas other carbapenems and faropenem may be ineffective.
• Zinc acetate potentiates the action of tosufloxacin Escherichia coli biofilm persisters.
  Usui M; Yokoo H; Tamura Y; Nakajima C; Suzuki Y; Ghigo JM; Beloin C
  Antimicrobial agents and chemotherapy, 63, 6, 2019年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Formation of bacterial biofilms is a major health threat due to their high levels of tolerance to multiple antibiotics and the presence of persisters responsible for infection relapses. We previously showed that a combination of starvation and induction of SOS response in biofilm led to increased levels of persisters and biofilm tolerance to fluoroquinolones. In this study, we hypothesized that inhibition of the SOS response may be an effective strategy to target biofilms and fluoroquinolone persister cells. We tested the survival of Escherichia coli biofilms to different classes of antibiotics in starved and nonstarved conditions and in the presence of zinc acetate, a SOS response inhibitor. We showed that zinc acetate potentiates, albeit moderately, the activity of fluoroquinolones against E. coli persisters in starved biofilms. The efficacy of zinc acetate to increase fluoroquinolone activity, particularly that of tosufloxacin, suggests that such a combination may be a potential strategy for treating biofilm-related bacterial infections.
• Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: potential for bovine inflammation therapy.
  Fujisawa S; Konnai S; Okagawa T; Maekawa N; Tanaka A; Suzuki Y; Murata S; Ohashi K
  BMC veterinary research, 15, 1, 68, 68, 2019年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Refractory diseases, including bacterial infections, are causing huge economic losses in dairy farming. Despite efforts to prevent and treat those diseases in cattle, including the use of antimicrobials, it is not well controlled in the field. Several inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), play important roles in disease progression; thus, blocking these cytokines can attenuate the acute and sever inflammation and may be a novel strategy for treatment. However, biological drugs targeting inflammatory cytokines have not been used in cattle. Therefore, in this study, bovine sTNFR1 and sTNFR2 IgG1 Fc-fusion proteins (TNFR1-Ig and TNFR2-Ig) were produced, and their anti-inflammatory functions were analyzed in vitro, to develop decoy receptors for bovine TNF-α. RESULTS: Both TNFR1-Ig and TNFR2-Ig were shown to bind with TNF-α, and TNFR2-Ig showed higher affinity toward TNF-α than TNFR1-Ig. We next stimulated murine fibroblast-derived cells (L929 cells) with TNF-α to induce cell death and analyzed cell viability in the presence of TNFR-Ig proteins. Both TNFR1-Ig and TNFR2-Ig suppressed TNF-α-induced cell death, significantly improving cell viability. In addition, cell death induced by TNF-α was suppressed, even at low TNFR2-Ig concentrations, suggesting TNFR2-Ig has higher activity to suppress TNF-α functions than TNFR1-Ig. Finally, to examine TNFR2-Ig's anti-inflammatory, we cultured peripheral blood mononuclear cells from cattle with TNF-α in the presence of TNFR2-Ig and analyzed the gene expression and protein production of the inflammatory cytokines IL-1β and TNF-α. TNFR2-Ig significantly reduced the gene expression and protein production of these cytokines. Our results suggest that TNFR2-Ig inhibits inflammatory cytokine kinetics by blocking TNF-α to transmembrane TNFR, thereby attenuating excessive inflammation induced by TNF-α. CONCLUSIONS: Collectively, the findings of this study demonstrated the potential of TNFR2-Ig as a novel therapeutic for inflammatory diseases, such as bovine clinical mastitis. Further investigation is required for future clinical application.
• Nosocomial Mycobacterium tuberculosis transmission by brief casual contact identified using comparative genomics.
  Seto J; Otani Y; Wada T; Suzuki Y; Ikeda T; Araki K; Mizuta K; Ahiko T
  The Journal of hospital infection, 2019年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Genetic diversity of Mycobacterium tuberculosis Central Asian Strain isolates from Nepal and comparison with neighboring countries.
  Shah Y; Poudel A; Maharjan B; Thapa J; Yamaguchi T; Diab HM; Pandey BD; Solo E; Isoda N; Suzuki Y; Nakajima C
  Transactions of the Royal Society of Tropical Medicine and Hygiene, 113, 4, 203, 211, 2019年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat for successful tuberculosis control worldwide. Central Asian Strain (CAS) has been reported as one of the dominant families contributing to MDR-TB in South Asia including Nepal, India and Pakistan. The aim of this study was to better understand the genetic characteristics of MDR-TB CAS family isolates circulating in Nepal and compare the results with neighboring countries. METHODS: A total of 145 MDR-TB CAS family isolates collected in Nepal from 2008 to 2013 were analyzed by spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) analysis. In addition, we compared these data with published data from India and Pakistan to investigate a possible epidemiological link via construction of a minimum spanning tree (MST). RESULTS: Spoligotyping analysis exhibited CAS1_Delhi SIT26 (n=60) as the predominant lineage among the MDR-TB CAS family in all three countries. However, the combined analysis with spoligotyping and MIRU-VNTR further discriminated 60 isolates into 49 different types and 5 clusters. Each cluster was composed of 14 isolates with a clustering rate of 23.3%, suggesting ongoing transmissions. Based on MST data from neighboring countries, we elucidated an evolutionary relationship between the two countries, Nepal and India, which could be explained by their open border. CONCLUSION: This study identified the evolutionary relationships among MDR-TB CAS1_Delhi subfamily isolates from Nepal and those from neighboring countries.
• 【結核・非結核性抗酸菌症-エキスパートが教える 実臨床に役立つ最新知見】結核・非結核性抗酸菌症の基礎研究 結核菌の薬剤耐性獲得
  山口 智之; 中島 千絵; 鈴木 定彦
  呼吸器ジャーナル, 66, 4, 650, 656, (株)医学書院, 2018年11月
  日本語
• Genetic diversity and distribution dynamics of multidrug-resistant Mycobacterium tuberculosis isolates in Nepal.
  Maharjan B; Nakajima C; Isoda N; Thapa J; Poudel A; Shah Y; Yamaguchi T; Shrestha B; Hoffmann H; Avsar K; Shrestha A; Gordon SV; Suzuki Y
  Scientific reports, 8, 1, 16634, 16634, 2018年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Multidrug-resistant tuberculosis (MDR-TB) is an emerging public health problem in Nepal. Despite the implementation of a successful TB control program in Nepal, notifications of MDR-TB are increasing, yet the reasons are unknown. The objective of this study was to understand the genetic diversity and epidemiological characteristics of MDR-Mycobacterium tuberculosis (MTB) isolates in Nepal. We isolated and genotyped 498 MDR-MTB isolates collected from April 2009 to March 2013 and analyzed the patients' background information. Our results showed that the lineage 2 (Beijing family) was the most predominant lineage (n = 241; 48.4%), followed by lineage 3 (n = 153, 30.7%). Lineage 4 was the third most prevalent (n = 73, 14.5%) followed by lineage 1 (n = 32, 6.4%). The lineages were significantly associated with geographic region, ethnic group, age and sex of patients. The Beijing genotype was found to have an important role in transmitting MDR-TB in Nepal and was significantly associated with the eastern region, mongoloid ethnic group and younger age group. We conclude that early diagnosis and treatment including molecular-epidemiological surveillance of MDR-TB cases will help to control transmission of MDR-TB in Nepal.
• A case of laboratory cross-contamination of Mycobacterium tuberculosis identified using comparative genomics.
  Seto J; Wada T; Suzuki Y; Ikeda T; Araki K; Umetsu Y; Ishikawa H; Mizuta K; Ahiko T
  The international journal of tuberculosis and lung disease, 22, 10, 1239, 1242, 2018年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Loop-mediated isothermal amplification for rapid identification of Mycobacterium tuberculosis in comparison with immunochromatographic SD Bioline MPT64 Rapid^® in a high burden setting.
  Phetsuksiri B; Rudeeaneksin J; Srisungngam S; Bunchoo S; Klayut W; Sangkitporn S; Nakajima C; Hamada S; Suzuki Y
  Japanese journal of infectious diseases, 72, 2, 112, 114, 2018年10月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Loop-mediated isothermal amplification (LAMP) was assessed for rapid identification of Mycobacterium tuberculosis complex (MTC) in comparison with an immunochromatographic test (ICT) using SD Bioline Ag MPT64 Rapid®. One hundred and fifty-one MGIT cultures positive for acid-fast bacilli were tested for MTC. DNA was extracted from a small portion of culture samples by heat lysis and subjected to LAMP analysis. Of these, 144 were positive and 5 were negative by both tests. One culture that was ICT negative but was LAMP positive was confirmed to have a mutation in the mpt64 gene. The agreement was 98.68% (95% confidence interval [CI]: 94.80-99.77), and the kappa value was 0.83% (95% CI: 0.59-1.00). Good correlation results suggested that LAMP assay is a reliable molecular test for rapid identification of MTC and is practical for use in resource-limited, high burden settings.
• Multiclonal Expansion and High Prevalence of β-Lactamase-Negative Haemophilus influenzae with High-Level Ampicillin Resistance in Japan and Susceptibility to Quinolones.
  Honda H; Sato T; Shinagawa M; Fukushima Y; Nakajima C; Suzuki Y; Shiraishi T; Kuronuma K; Takahashi S; Takahashi H; Yokota SI
  Antimicrobial agents and chemotherapy, 62, 9, 2018年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, β-Lactam-resistant Haemophilus influenzae is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) isolates in Japan has been reported. However, the reasons for the expansion are unknown. High-BLNAR strains possess an amino acid substitution, either Asn526Lys (group III) or Arg517His (group III-like) in addition to Ser385Thr, in penicillin-binding protein 3 (PBP3). To determine the current prevalence of high-BLNAR strains and the mechanisms behind their expansion in Japan, their prevalence, PBP3 types, multilocus sequence types, and susceptibilities to quinolones approved in Japan as alternatives were determined. Sixty percent of H. influenzae clinical isolates (62/104 isolates) were β-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) strains. Among BLNAR isolates, 92% (57/62 isolates) were high-BLNAR strains. Most isolates were classified as belonging to group III, which contained many genotypes (11 PBP3 types and 25 sequence types). These results indicated that the expansion of high-BLNAR isolates was multiclonal and such strains are still predominant in Japanese clinical settings. One high-BLNAR isolate harbored the novel amino acid substitution Asn526Met in addition to Ser385Thr in PBP3, suggesting a new group (group IV). No quinolone-resistant H. influenzae isolates were identified. The MICs for the quinolones (moxifloxacin, garenoxacin, and tosufloxacin) were similar to that for levofloxacin, whereas sitafloxacin exhibited a lower MIC. However, we obtained 4 H. influenzae isolates with decreased quinolone susceptibility with the amino acid substitution Ser84Leu in GyrA, and 3 of those isolates were high-BLNAR isolates. In summary, this study shows that multiclonal high-BLNAR strains predominate in a Japanese university hospital. Isolates remain sensitive to quinolones, but vigilance is required to prevent the development of fluoroquinolone resistance in high-BLNAR strains.
• Establishment of a mouse-tick infection model for Theileria orientalis and analysis of its transcriptome.
  Hayashida K; Umemiya-Shirafuji R; Sivakumar T; Yamagishi J; Suzuki Y; Sugimoto C; Yokoyama N
  International journal for parasitology, 2018年08月, ［査読有り］
• Whole genome analysis of a multidrug-resistant Streptococcus pneumoniae isolate from a patient with invasive pneumococcal infection developing disseminated intravascular coagulation.
  Yasuo Ohkoshi; Toyotaka Sato; Takayuki Wada; Yukari Fukushima; Hiromi Murabayashi; Yasunari Takakuwa; Kaoru Nishiyama; Hiroyuki Honda; Tsukasa Shiraishi; Koji Kuronuma; Hiroki Takahashi; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 24, 8, 674, 681, 2018年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Multidrug-resistant Streptococcus pneumoniae strains were isolated from blood and sputum of a patient with disseminated intravascular coagulation in Sapporo city, Japan. These antibiograms were only susceptible to vancomycin, linezolid, daptomycin, some carbapenems, and some fluoroquinolones. Identical antibiograms, serotypes (19F), and sequence types (ST10017) suggested a shared origin of these isolates. Only one ST10017 strain has been isolated in the same city in Japan previously (2014), and the 2014 isolate is still susceptible to macrolides. The whole genome of the blood-derived isolate was sequenced. The strain harbored resistance mutations in parC, gyrA, pbp1a, pbp2a, pbp2b, and pbp2x, and harbored the resistance genes, ermB and tetM. The nucleotide sequences of parC and pbp2x genes of strain MDRSPN001 were clearly different from those of other S. pneumoniae strains and were similar to those of oral streptococci strains. These findings suggest that strain MDRSPN001 has been rapidly and drastically evolving multidrug resistance by gene replacement and accumulation of genes originating from other strains, such as oral streptococci, Streptococcus mitis.
• Phylogenetic uniqueness of Mycobacterium avium subspecies hominissuis isolated from an abnormal pulmonary bovine case.
  Shiomi Yoshida; Tsubasa Araki; Tomohito Asai; Kazunari Tsuyuguchi; Kentaro Arikawa; Tomotada Iwamoto; Chie Nakajima; Yasuhiko Suzuki; Kenji Ohya; Tokuma Yanai; Takayuki Wada; Taro Yamamoto
  Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 62, 122, 129, 2018年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Mycobacterium avium subspecies hominissuis (MAH) is an important cause of infection in human pulmonary and swine intestinal cases. Although MAH is isolated from environmental sources frequently, infections of other animals have rarely been analysed. Recently, we detected granulomatous inflammation in bovine lung as an abnormal postmortem inspection case. To ascertain its genetic profile, we conducted a variable numbers of tandem repeats (VNTR) analysis and genomic characterization using deep sequencing. The VNTR type was a unique profile that differed from reported genotypes, but it was assigned within a broad genotypic complex of isolates from human patients and bathrooms. Genomic comparison with 116 registered genome sequences of the subspecies revealed that the strain was separate from five major genetic population groups proposed previously. Although the infection source remains unclear, its isolation from various resources such as animal infection cases should be elucidated more extensively to reveal its genetic diversity and ecological context.
• Characterization of mutations conferring streptomycin resistance to multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar
  Nan Aye Thida Oo; Lai Lai San; Jeewan Thapa; Khin Saw Aye; Wah Wah Aung; Chie Nakajima; Yasuhiko Suzuki
  Tuberculosis, 111, 8, 13, Churchill Livingstone, 2018年07月01日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Antibacterial Activity of DC-159a Against Salmonella Typhimurium.
  Koide K; Kongsoi S; Ouchi Y; Yamaguchi T; Nakajima C; Suzuki Y
  Microbial drug resistance (Larchmont, N.Y.), 25, 1, 14, 22, 2018年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Cooperation of PD-1 and LAG-3 in the exhaustion of CD4+ and CD8+ T cells during bovine leukemia virus infection.
  Tomohiro Okagawa; Satoru Konnai; Asami Nishimori; Naoya Maekawa; Shinya Goto; Ryoyo Ikebuchi; Junko Kohara; Yasuhiko Suzuki; Shinji Yamada; Yukinari Kato; Shiro Murata; Kazuhiko Ohashi
  Veterinary research, 49, 1, 50, 50, 2018年06月19日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection. In this study, multi-color flow cytometric analyses of PD-1- and LAG-3-expressing T cells were performed in BLV-infected cattle at different stages of the disease. The frequencies of PD-1+LAG-3+ heavily exhausted T cells among CD4+ and CD8+ T cells was higher in the blood of cattle with B-cell lymphoma over that of BLV-uninfected and BLV-infected cattle without lymphoma. In addition, blockade assays of peripheral blood mononuclear cells were performed to examine whether inhibition of the interactions between PD-1 and LAG-3 and their ligands by blocking antibodies could restore T-cell function during BLV infection. Single or dual blockade of the PD-1 and LAG-3 pathways reactivated the production of Th1 cytokines, interferon-γ and tumor necrosis factor-α, from BLV-specific T cells of the infected cattle. Taken together, these results indicate that PD-1 and LAG-3 cooperatively mediate the functional exhaustion of CD4+ and CD8+ T cells and are associated with the development of B-cell lymphoma in BLV-infected cattle.
• Insight into multidrug-resistant Beijing genotype Mycobacterium tuberculosis isolates in Myanmar.
  San LL; Aye KS; Oo NAT; Shwe MM; Fukushima Y; Gordon SV; Suzuki Y; Nakajima C
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 76, 109, 119, 2018年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: Myanmar is a World Health Organization high tuberculosis (TB) burden country with a high multidrug-resistant (MDR)-TB burden. Of significance, a high prevalence of the Beijing genotype of Mycobacterium tuberculosis (MTB) among MDR-MTB has been reported previously. A detailed genetic characterization of TB clinical isolates was performed in order to explore whether there is an association between the prevalence of the Beijing MTB genotype and MDR-TB in Myanmar. METHODS: A total of 265 MDR-MTB clinical isolates collected in 2010 and 2012 were subjected to spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis, single nucleotide polymorphism (SNP) typing, and drug resistance-associated gene sequencing, including rpoC to detect potential compensatory evolution. RESULTS: Of the total MDR-MTB isolates, 79.2% (210/265) were of the Beijing genotype, the majority of which were the 'modern' subtype. Beijing genotype isolates were differentiated by 15-locus MIRU-VNTR and a high clustering rate (53.0%) was observed in the modern subtype. These MIRU-VNTR patterns were similar to Beijing genotype clones spreading across Russia and Central Asia. A high prevalence of katG Ser315Thr, and genetic evidence of extensive drug resistance (XDR) and pre-XDR and compensatory mutations in rpoC were observed among clustered isolates. CONCLUSIONS: MDR-MTB strains of the Beijing genotype might be spreading in Myanmar and present a major challenge to TB control in this country.
• Prostaglandin E2 Induction Suppresses the Th1 Immune Responses in Cattle with Johne's Disease.
  Yamato Sajiki; Satoru Konnai; Tomohiro Okagawa; Asami Nishimori; Naoya Maekawa; Shinya Goto; Ryoyo Ikebuchi; Reiko Nagata; Satoko Kawaji; Yumiko Kagawa; Shinji Yamada; Yukinari Kato; Chie Nakajima; Yasuhiko Suzuki; Shiro Murata; Yasuyuki Mori; Kazuhiko Ohashi
  Infection and immunity, 86, 5, 2018年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis, is a bovine chronic infection that is endemic in Japan and many other countries. The expression of immunoinhibitory molecules is upregulated in cattle with Johne's disease, but the mechanism of immunosuppression is poorly understood. Prostaglandin E2 (PGE2) is immunosuppressive in humans, but few veterinary data are available. In this study, functional and kinetic analyses of PGE2 were performed to investigate the immunosuppressive effect of PGE2 during Johne's disease. In vitro PGE2 treatment decreased T-cell proliferation and Th1 cytokine production and upregulated the expression of immunoinhibitory molecules such as interleukin-10 and programmed death ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMCs) from healthy cattle. PGE2 was upregulated in sera and intestinal lesions of cattle with Johne's disease. In vitro stimulation with Johnin purified protein derivative (J-PPD) induced cyclooxygenase-2 (COX-2) transcription, PGE2 production, and upregulation of PD-L1 and immunoinhibitory receptors in PBMCs from cattle infected with M. avium subsp. paratuberculosis Therefore, Johnin-specific Th1 responses could be limited by the PGE2 pathway in cattle. In contrast, downregulation of PGE2 with a COX-2 inhibitor promoted J-PPD-stimulated CD8+ T-cell proliferation and Th1 cytokine production in PBMCs from the experimentally infected cattle. PD-L1 blockade induced J-PPD-stimulated CD8+ T-cell proliferation and interferon gamma production in vitro Combined treatment with a COX-2 inhibitor and anti-PD-L1 antibodies enhanced J-PPD-stimulated CD8+ T-cell proliferation in vitro, suggesting that the blockade of both pathways is a potential therapeutic strategy to control Johne's disease. The effects of COX-2 inhibition warrant further study as a novel treatment of Johne's disease.
• Genotypic characterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia
  Precious Bwalya; Tomoyuki Yamaguchi; Georgina Mulundu; Chie Nakajima; Grace Mbulo; Eddie Samuneti Solo; Yukari Fukushima; Kunda Kasakwa; Yasuhiko Suzuki
  Tuberculosis, 109, 117, 122, Churchill Livingstone, 2018年03月01日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Tuberculosis Caused by Mycobacterium orygis in Dairy Cattle and Captured Monkeys in Bangladesh: a New Scenario of Tuberculosis in South Asia
  Z. Rahim; J. Thapa; Y. Fukushima; A. G. M. van der Zanden; S. V. Gordon; Y. Suzuki; C. Nakajima
  TRANSBOUNDARY AND EMERGING DISEASES, 64, 6, 1965, 1969, 2017年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Complete Genome Sequence of Multidrug-Resistant Streptococcus pneumoniae Serotype 19F Isolated from an Invasive Infection in Sapporo, Japan.
  Toyotaka Sato; Yasuo Ohkoshi; Takayuki Wada; Yukari Fukushima; Hiromi Murabayashi; Yasunari Takakuwa; Kaoru Nishiyama; Tsukasa Shiraishi; Chie Nakajima; Yasuhiko Suzuki; Shin-Ichi Yokota
  Genome announcements, 5, 44, 2017年11月02日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Invasive infection of multidrug-resistant Streptococcus pneumoniae is a serious clinical concern. Here, we report the complete genome sequence of a multidrug-resistant S. pneumoniae serotype 19F strain isolated from a patient with an invasive infection in Sapporo, Japan.
• Quinolone Resistance Determinants of Clinical Salmonella Enteritidis in Thailand
  Fuangfa Utrarachkij; Chie Nakajima; Ruchirada Changkwanyeun; Kanokrat Siripanichgon; Siriporn Kongsoi; Srirat Pornruangwong; Kanjana Changkaew; Risa Tsunoda; Yutaka Tamura; Orasa Suthienkul; Yasuhiko Suzuki
  MICROBIAL DRUG RESISTANCE, 23, 7, 885, 894, 2017年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• High diversity of multidrug-resistant Mycobacterium tuberculosis Central Asian Strain isolates in Nepal
  Yogendra Shah; Bhagwan Maharjan; Jeewan Thapa; Ajay Poudel; Hassan Mahmoud Diab; Basu Dev Pandey; Eddie S. Solo; Norikazu Isoda; Yasuhiko Suzuki; Chie Nakajima
  INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 63, 13, 20, 2017年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• ANTIMICROBIAL RESISTANCE, INTEGRON, VIRULENCE GENE, AND MULTILOCUS SEQUENCE TYPING OF &ITESCHERICHIA COLI&IT ISOLATES FROM POSTWEANING PIGLETS WITH AND WITHOUT DIARRHEA
  Watsawan Prapasawat; Apiradee Intarapuk; Pornthip Chompook; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  SOUTHEAST ASIAN JOURNAL OF TROPICAL MEDICINE AND PUBLIC HEALTH, 48, 5, 1042, 1055, 2017年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.
  Goto S; Konnai S; Okagawa T; Nishimori A; Maekawa N; Gondaira S; Higuchi H; Koiwa M; Tajima M; Kohara J; Ogasawara S; Kato Y; Suzuki Y; Murata S; Ohashi K
  Immunity, inflammation and disease, 5, 3, 355, 363, 2017年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis. METHODS: In the initial experiments, we used enzyme-linked immunosorbent assay to measure interferon-γ (IFN-γ) from peripheral blood mononuclear cells (PBMCs) isolated from cattle with mycoplasmosis. RESULTS: Expectedly, IFN-γ production significantly decreased in cattle with mycoplasmosis compared with that in clinically healthy cattle. Concomitantly, flow cytometric analysis revealed that the proportions of PD-1+ CD4+ and PD-L1+ CD14+ cells significantly increased in peripheral blood of the infected cattle. Interestingly, the number of PD-1+ CD4+ and PD-1+ CD8+ T cells were negatively correlated with IFN-γ production from PBMCs in bovine mycoplasmosis. Additionally, blockade of the PD-1/PD-L1 pathway in vitro by anti-bovine PD-1- and anti-bovine PD-L1 antibodies significantly upregulated the production of IFN-γ from anti-mycoplasma-specific cells. CONCLUSIONS: These results suggest that the PD-1/PD-L1 pathway could be involved in immune exhaustion of bovine mycoplasma-specific T cells. In conclusion, our study opens up a new perspective in the therapeutic strategy for bovine mycoplasmosis by targeting the immunoinhibitory receptor pathways.
• Population Structure and Local Adaptation of MAC Lung Disease Agent Mycobacterium avium subsp hominissuis
  Hirokazu Yano; Tomotada Lwamoto; Yukiko Nishiuchi; Chie Nakajima; Daria A. Starkova; Igor Mokrousov; Olga Narvskaya; Shiomi Yoshida; Kentaro Arikawa; Noriko Nakanishi; Ken Osaki; Ichiro Nakagawa; Manabu Ato; Yasuhiko Suzuki; Fumito Maruyama
  GENOME BIOLOGY AND EVOLUTION, 9, 9, 2403, 2417, 2017年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Convenient PCR method for variable-number tandem-repeat typing of Mycobacterium tuberculosis clinical isolates.
  Seto J; Wada T; Suzuki Y; Ikeda T; Mizuta K; Mitarai S; Ahiko T
  Journal of microbiological methods, 139, 12, 14, 2017年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
  Naoya Maekawa; Satoru Konnai; Satoshi Takagi; Yumiko Kagawa; Tomohiro Okagawa; Asami Nishimori; Ryoyo Ikebuchi; Yusuke Izumi; Tatsuya Deguchi; Chie Nakajima; Yukinari Kato; Keiichi Yamamoto; Hidetoshi Uemura; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  SCIENTIFIC REPORTS, 7, 1, 8951, 8951, 2017年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A quantitative and efficient approach to select MIRU-VNTR loci based on accumulation of the percentage differences of strains for discriminating divergent Mycobacterium tuberculosis sublineages
  Xin-Ling Pan; Chun-Lei Zhang; Chie Nakajima; Jin Fu; Chang-Xia Shao; Li-Na Zhao; Jia-Yi Cui; Na Jiao; Chang-Long Fan; Yasuhiko Suzuki; Toshio Hattori; Di Li; Hong Ling
  EMERGING MICROBES & INFECTIONS, 6, 7, e68, 2017年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Evaluation of in-house loop-mediated isothermal amplification for tuberculosis diagnosis in comparison with Xpert MTB/RIF
  Habeenzu C; Nakajima C; Solo E; Bwalya P; Kajino, K; Miller M; Kurosawa Y; Mudenda V; Kasonka L; Suzuki Y; Matsuba T
  Journal of Infection in Developing Countries, 11, 6, 440, 444, 2017年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: To evaluate the diagnostic performances of an in-house loop-mediated isothermal amplification (LAMP) kit and the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in a resource-limited setting, this study was performed at the University Teaching Hospital, Ministry of Health, the Republic of Zambia. METHODOLOGY: Two hundred sputum specimens obtained from new tuberculosis (TB) suspects were used for the evaluation of the diagnostic performance of an in-house LAMP kit in comparison with the Xpert MTB/RIF kit. RESULTS: The sensitivity of in-house LAMP and Xpert MTB/RIF was 96.9% and 95.4% in smear-positive samples, 96.8% and 100% in smear-positive/culture-positive samples, and 39.1% and 73.9% in smear-negative/culture-positive samples, respectively. The specificity of in-house LAMP and MTB/RIF kits with culture was 96.5% and 94.5%, respectively. This indicated the superiority of the Xpert MTB/RIF kit; however, mechanical errors during sample processing and the insufficient quantity of samples by Xpert MTB/RIF kit occurred at 2.0% and 19.7%, respectively, comparing to the 100% accessibility of in-house LAMP. CONCLUSIONS: Considering the results obtained in this study together with the easy setup with much simpler equipment, such as an aluminum heat block or water bath, in in-house LAMP compared with real-time polymerase chain reaction equipment in Xpert MTB/RIF kit, the applicability of in-house LAMP for the screening of tuberculosis directly from sputum in resource-limited setting seemed to be high.
• Anti-Bovine Programmed Death-1 Rat-Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle
  Tomohiro Okagawa; Satoru Konnai; Asami Nishimori; Naoya Maekawa; Ryoyo Ikebuchi; Shinya Goto; Chie Nakajima; Junko Kohara; Satoshi Ogasawara; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  FRONTIERS IN IMMUNOLOGY, 8, 650, 650, 2017年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study
  Jingge Zhao; Takashi Matsuba; Xiaoyan Zhang; Susan Leano; Chie Nakajima; Haorile Chagan-Yasutan; Elizabeth Freda Telan; Yasuhiko Suzuki; Toshio Hattori
  BMC INFECTIOUS DISEASES, 17, 1, 344, 344, 2017年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) ratbovine chimeric antibody against bovine leukemia virus infection
  Asami Nishimori; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Ryoyo Ikebuchi; Shinya Goto; Yamato Sajiki; Yasuhiko Suzuki; Junko Kohara; Satoshi Ogasawara; Yukinari Kato; Shiro Murata; Kazuhiko Ohashi
  PLOS ONE, 12, 4, e0174916, 2017年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Survival and prevalence of Clostridium difficile in manure compost derived from pigs
  Masaru Usui; Mayuko Kawakura; Nobuki Yoshizawa; Lai Lai San; Chie Nakajima; Yasuhiko Suzuki; Yutaka Tamura
  ANAEROBE, 43, 15, 20, 2017年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.
  Goto, S; Konnai, S; Okagawa, T; Nishimori, A; Maekawa, N; Gondaira, S; Higuchi, H; Koiwa, M; Tajima, M; Kohara, J; Ogasawara, S; Kato, Y; Suzuki, Y; Murata, S; Ohashi, K
  Immunity, Inflammation and Disease, 10, 1, 9, 2017年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Genotypic diversity of Mycobacterium tuberculosis strains in Myanmar
  Thanda Tun; Khin Saw Aye; Wint Wint Nyunt; John A. Crump; Chie Nakajima; Yasuhiko Suzuki; Kyi Kyi Thinn; Gregory M. Cook; Htin Lin Aung
  INFECTIOUS DISEASES, 49, 3, 237, 239, 2017年, ［査読有り］, ［国際誌］
  英語
• Immunological Roles of Elevated Plasma Levels of Matricellular Proteins in Japanese Patients with Pulmonary Tuberculosis
  Beata Shiratori; Jingge Zhao; Masao Okumura; Haorile Chagan-Yasutan; Hideki Yanai; Kazue Mizuno; Takashi Yoshiyama; Tadashi Idei; Yugo Ashino; Chie Nakajima; Yasuhiko Suzuki; Toshio Hattori
  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 18, 1, 2017年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Collectin Kidney 1 Plays an Important Role in Innate Immunity against Streptococcus pneumoniae Infection
  Insu Hwang; Kenichiro Mori; Katsuki Ohtani; Yasuyuki Matsuda; Nitai Roy; YounUck Kim; Yasuhiko Suzuki; Nobutaka Wakamiya
  JOURNAL OF INNATE IMMUNITY, 9, 2, 217, 228, 2017年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Difference in Antibody Responses to Mycobacterium tuberculosis Antigens in Japanese Tuberculosis Patients Infected with the Beijing/Non-Beijing Genotype
  Jingge Zhao; Beata Shiratori; Masao Okumura; Hideki Yanai; Makoto Matsumoto; Chie Nakajima; Kazue Mizuno; Kenji Ono; Tetsuya Oda; Haorile Chagan-Yasutan; Yugo Ashino; Takashi Matsuba; Takashi Yoshiyama; Yasuhiko Suzuki; Toshio Hattori
  JOURNAL OF IMMUNOLOGY RESEARCH, 2017, 4797856, 4797856, 2017年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Quinolone resistance-associated amino acid substitutions affect enzymatic activity of Mycobacterium leprae DNA gyrase
  Tomoyuki Yamaguchi; Kazumasa Yokoyama; Chie Nakajima; Yasuhiko Suzuki
  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 81, 7, 1343, 1347, 2017年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A PCR-based survey of animal African trypanosomosis and selected piroplasm parasites of cattle and goats in Zambia
  Simon Peter Musinguzi; Keisuke Suganuma; Masahito Asada; Dusit Laohasinnarong; Thillaiampalam Sivakumar; Naoaki Yokoyama; Boniface Namangala; Chihiro Sugimoto; Yasuhiko Suzuki; Xuenan Xuan; Noboru Inoue
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 12, 1819, 1824, 2016年12月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Molecular epidemiology of pathogenic Leptospira spp. among large ruminants in the Philippines
  Marvin A. Villanueva; Claro N. Mingala; Michelle M. Balbin; Chie Nakajima; Norikazu Isoda; Yasuhiko Suzuki; Nobuo Koizumi
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 11, 1649, 1655, 2016年11月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Amino acid substitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium
  Siriporn Kongsoi; Ruchirada Changkwanyeun; Kazumasa Yokoyama; Chie Nakajima; Kanjana Changkaew; Orasa Suthienkul; Yasuhiko Suzuki
  DRUG TESTING AND ANALYSIS, 8, 10, 1065, 1070, 2016年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni
  Ruchirada Changkwanyeun; Tomoyuki Yamaguchi; Siriporn Kongsoi; Kanjana Changkaew; Kazumasa Yokoyama; Hyun Kim; Orasa Suthienkul; Masaru Usui; Yutaka Tamura; Chie Nakajima; Yasuhiko Suzuki
  DRUG TESTING AND ANALYSIS, 8, 10, 1071, 1076, 2016年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients.
  Chagan-Yasutan H; Chen Y; Lacuesta TL; Leano PS; Iwasaki H; Hanan F; Taurustiati D; Ohmoto Y; Ashino Y; Saitoh H; Kiyomoto H; Suzuki Y; Telan FO; Hattori T
  International journal of molecular sciences, 17, 10, 2016年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae
  Tomoyuki Yamaguchi; Kazumasa Yokoyama; Chie Nakajima; Yasuhiko Suzuki
  PLoS Neglected Tropical Diseases, 10, 9, e0005013, Public Library of Science, 2016年09月28日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• The effects of administering lactic acid bacteria sealed in a capsule on the intestinal bacterial flora of cattle
  Seyama Tomohiro; Hirayasu Hirofumi; Yoshida Gen; Ohnuma Aiko; Qiu Yongjin; Nakajima Chie; Kasai Koji; Suzuki Yasuhiko
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 64, 3, 197, 203, 2016年08月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Development and evaluation of an interferon-γ release assay in Asian elephants (Elephas maximus).
  Paudel S; Villanueva MA; Mikota SK; Nakajima C; Gairhe KP; Subedi S; Rayamajhi N; Sashika M; Shimozuru M; Matsuba T; Suzuki Y; Tsubota T
  The Journal of veterinary medical science, 78, 7, 1117, 1121, 2016年07月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Collectin CL-P1 utilizes C-reactive protein for complement activation
  Nitai Roy; Katsuki Ohtani; Yasuyuki Matsuda; Kenichiro Mori; Insu Hwang; Yasuhiko Suzuki; Norimitsu Inoue; Nobutaka Wakamiya
  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1860, 6, 1118, 1128, 2016年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Collectin CL-P1 utilizes C-reactive protein for complement activation.
  Nitai Roy; Katsuki Ohtani; Yasuyuki Matsuda; Kenichiro Mori; Insu Hwang; Yasuhiko Suzuki; Norimitsu Inoue; Nobutaka Wakamiya
  Biochimica et biophysica acta, 1860, 6, 1118, 28, 2016年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: C-reactive protein (CRP) is a plasma pentraxin family protein that is massively induced as part of the innate immune response to infection and tissue injury. CRP and other pentraxin proteins can activate a complement pathway through C1q, collectins, or on microbe surfaces. It has been found that a lectin-like oxidized LDL receptor 1 (LOX-1), which is an endothelial scavenger receptor (SR) having a C-type lectin-like domain, interacts with CRP to activate the complement pathway using C1q. However it remains elusive whether other lectins or SRs are involved in CRP-mediated complement activation and the downstream effect of the complement activation is also unknown. METHODS: We prepared CHO/ldlA7 cells expressing collectin placenta-1 (CL-P1) and studied the interaction of CRP with cells. We further used ELISA for testing binding between proteins. We tested for C3 fragment deposition and terminal complement complex (TCC) formation on HEK293 cells expressing CL-P1. RESULTS: Here, we demonstrated that CL-P1 bound CRP in a charge dependent manner and the interaction of CRP with CL-P1 mediated a classical complement activation pathway through C1q and additionally drove an amplification pathway using properdin. However, CRP also recruits complement factor H (CFH) on CL-P1 expressing cell surfaces, to inhibit the formation of a terminal complement complex in normal complement serum conditions. GENERAL SIGNIFICANCE: The interaction of collectin CL-P1 with CFH might be key for preventing attack on "self" as a result of complement activation induced by the CL-P1 and CRP interaction.
• Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma
  Naoya Maekawa; Satoru Konnai; Tomohiro Okagawa; Asami Nishimori; Ryoyo Ikebuchi; Yusuke Izumi; Satoshi Takagi; Yumiko Kagawa; Chie Nakajima; Yasuhiko Suzuki; Yukinari Kato; Shiro Murata; Kazuhiko Ohashi
  PLOS ONE, 11, 6, e0157176, 2016年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Antigenic characterization of dimorphic surface protein in Mycobacterium tuberculosis
  Takashi Matsuba; Umme Ruman Siddiqi; Toshio Hattori; Chie Nakajima; Jun Fujii; Yasuhiko Suzuki
  FEMS MICROBIOLOGY LETTERS, 363, 10, 2016年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Combined antibody and DNA detection for early diagnosis of leptospirosis after a disaster
  Hiroko Iwasaki; Haorile Chagan-Yasutan; Prisca Susan A. Leano; Nobuo Koizumi; Chie Nakajima; Delsi Taurustiati; Firmanto Hanan; Talitha Lea Lacuesta; Yugo Ashino; Yasuhiko Suzuki; Nina G. Gloriani; Elizabeth Freda O. Telan; Toshio Hattori
  DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 84, 4, 287, 291, 2016年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Genetic diversity and antimicrobial resistance pattern of Salmonella enterica serovar Enteritidis clinical isolates in Thailand
  Fuangfa Utrarachkij; Chie Nakajima; Kanokrat Siripanichgon; Kanjana Changkaew; Yuwanda Thongpanich; Srirat Pornraungwong; Orasa Suthienkul; Yasuhiko Suzuki
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 22, 4, 209, 215, 2016年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Development of Point-of-Care Testing for Disaster-Related Infectious Diseases
  Toshio Hattori; Haorile Chagan-Yasutan; Beata Shiratori; Shinichi Egawa; Takako Izumi; Toru Kubo; Chie Nakajima; Yasuhiko Suzuki; Toshiro Niki; Bachti Alisjahbana; Elizabeth Telan
  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 238, 4, 287, 293, 2016年04月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar
  Khin Saw Aye; Chie Nakajima; Tomoyuki Yamaguchi; Min Min Win; Mu Mu Shwe; Aye Aye Win; Thandar Lwin; Wint Wint Nyunt; Ti Ti; Yasuhiko Suzuki
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 22, 3, 174, 179, 2016年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Mycobacterium orygis-Associated Tuberculosis in Free-Ranging Rhinoceros, Nepal, 2015
  Jeewan Thapa; Sarad Paudel; Amir Sadaula; Yogendra Shah; Bhagwan Maharjan; Gretchen E. Kaufman; Deborah McCauley; Kamal P. Gairhe; Toshio Tsubota; Yasuhiko Suzuki; Chie Nakajima
  EMERGING INFECTIOUS DISEASES, 22, 3, 570, 572, 2016年03月, ［査読有り］, ［国際誌］
  英語
• Ungulate malaria parasites
  Thomas J. Templeton; Masahito Asada; Montakan Jiratanh; Sohta A. Ishikawa; Sonthaya Tiawsirisup; Thillaiampalam Sivakumar; Boniface Namangala; Mika Takeda; Kingdao Mohkaew; Supawan Ngamjituea; Noboru Inoue; Chihiro Sugimoto; Yuji Inagaki; Yasuhiko Suzuki; Naoaki Yokoyama; Morakot Kaewthamasorn; Osamu Kaneko
  SCIENTIFIC REPORTS, 6, 23230, 23230, 2016年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Adenocarcinoma arising in urinary bladder endocervicosis
  Masato Nakaguro; Toyonori Tsuzuki; Satoko Shimada; Tetsuro Taki; Mari Tsuchiyama; Atsuko Kitamura; Yasuhiko Suzuki; Yojiro Nakano; Kenzo Ono
  PATHOLOGY INTERNATIONAL, 66, 2, 108, 113, 2016年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Serological investigation of Leptospira infection and its circulation in one intensive-type water buffalo farm in the Philippines
  Marvin A. Villanueva; Claro N. Mingala; Nina G. Gloriani; Yasutake Yanagihara; Norikazu Isoda; Chie Nakajima; Yasuhiko Suzuki; Nobuo Koizumi
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 64, 1, 15, 24, 2016年02月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Detection of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Market-Ready Chickens in Zambia
  K. Chishimba; B. M. Hang'Ombe; K. Muzandu; S. E. Mshana; M. I. Matee; C. Nakajima; Y. Suzuki
  International Journal of Microbiology, 2016, Hindawi Limited, 2016年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Pathogenic lineage of mcr-negative colistin-resistant Escherichia coli, Japan, 2008-2015
  Sato T; Fukuda A; Suzuki Y; Shiraishi T; Honda H; Shinagawa M; Yamamoto S; Ogasawara N; Usui M; Takahashi H; Takahashi S; Tamura Y; Yokota S
  Emerging Infectioud Diseases, 22, 12, 2223, 2226, 2016年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Genetic diversity of Vibrio parahaemolyticus strains isolated from farmed Pacific white shrimp and ambient pond water affected by acute hepatopancreatic necrosis disease outbreak in Thailand
  Kaknokrat Chonsin; Shigeaki Matsuda; Chonchanok Theethakaew; Toshio Kodama; Jiraphan Junjhon; Yasuhiko Suzuki; Orasa Suthienkul; Tetsuya Iida
  FEMS MICROBIOLOGY LETTERS, 363, 2, fnv222, 2016年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• First insight into the genetic population structure of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in Egypt
  Hassan Mahmoud Diab; Chie Nakajima; Saber A. Kotb; Alaa Mokhtar; Nagwa F. M. Khder; Ahmed S. A. Abdelaal; Azza Hegazy; Ajay Poudel; Yogendra Shah; Yasuhiko Suzuki
  TUBERCULOSIS, 96, 13, 20, 2016年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Multiple-locus variable-number tandem repeat analysis of Leptospira interrogans and Leptospira borgpetersenii isolated from small feral and wild mammals in East Asia
  Nobuo Koizumi; Hidemasa Izumiya; Jung-Jung Mu; Zbigniew Arent; Shou Okano; Chie Nakajima; Yasuhiko Suzuki; Maki Mizutani Muto; Tsutomu Tanikawa; Kyle R. Taylor; Noriyuki Komatsu; Kumiko Yoshimatsu; Hoang Thi Thu Ha; Makoto Ohnishi
  INFECTION GENETICS AND EVOLUTION, 36, 434, 440, 2015年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• No crucial amino acid changes in the predicted histo blood group antigen-binding sites of norovirus genotype GII.4 capsid between non-secretors and secretors origin might suggest an alternative route of infection or existence of coincidental molecules
  Tomoko Yoda; Yasuhiko Suzuki; Ikuko Aoyama; Kenji Yamazaki; Shuji Nakata; Kazuo Takahashi
  JOURNAL OF MEDICAL MICROBIOLOGY, 64, 12, 1544, 1547, 2015年12月, ［査読有り］, ［国際誌］
  英語
• Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis
  Muhammad Andrian Senoputra; Beata Shiratori; Fakhrial Mirwan Hasibuan; Raspati Cundarani Koesoemadinata; Lika Apriani; Yugo Ashino; Kenji Ono; Tetsuya Oda; Makoto Matsumoto; Yasuhiko Suzuki; Bachti Alisjahbana; Toshio Hattori
  DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 83, 3, 278, 285, 2015年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin-Producing Strains of Escherichia coli O157:H7 in Japan
  Ryuji Kawahara; Kazuko Seto; Masumi Taguchi; Chie Nakajima; Yuko Kumeda; Yasuhiko Suzuki
  JOURNAL OF CLINICAL MICROBIOLOGY, 53, 9, 3035, 3038, 2015年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
  Siriporn Kongsoi; Kazumasa Yokoyama; Apinun Suprasert; Fuangfa Utrarachkij; Chie Nakajima; Orasa Suthienkul; Yasuhiko Suzuki
  DRUG TESTING AND ANALYSIS, 7, 8, 714, 720, 2015年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones
  Ruchirada Changkwanyeun; Masaru Usui; Siriporn Kongsoi; Kazumasa Yokoyama; Hyun Kim; Orasa Suthienkul; Kanjana Changkaew; Chie Nakajima; Yutaka Tamura; Yasuhiko Suzuki
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 21, 8, 604, 609, 2015年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Antimicrobial Resistance, Extended-Spectrum β-Lactamase Productivity, and Class 1 Integrons in Escherichia coli from Healthy Swine.
  Changkaew K; Intarapuk A; Utrarachkij F; Nakajima C; Suthienkul O; Suzuki Y
  Journal of food protection, 78, 8, 1442, 1450, 2015年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Molecular characterization of Mycobacterium orygis isolates from wild animals of Nepal
  Jeewan Thapa; Chie Nakajima; Bhagwan Maharjan; Ajay Poudel; Yasuhiko Suzuki
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 63, 3, 151, 158, 2015年08月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• A case of Manila type Mycobacterium tuberculosis infection in Japan.
  Usami O; Nakajima C; Endo S; Inomata S; Kanamori H; Hirakata Y; Uchiyama B; Kaku M; Suzuki Y; Hattori T
  Clinical case reports, 3, 7, 622, 625, 2015年07月, ［査読有り］, ［国際誌］
  英語, A 76-year-old Japanese woman contracted a Mycobacterium tuberculosis (TB, Manila type) infection in Japan, despite never having traveled. However, her son was treated for TB in the Philippines 3 years before he stayed at her house. Spoligotyping allows us to identify the TB genotype and identify the route of infection.
• Molecular epidemiology of pathogenic Leptospira spp. in the straw-colored fruit bat (Eidolon helvum) migrating to Zambia from the Democratic Republic of Congo
  Hirohito Ogawa; Nobuo Koizumi; Aiko Ohnuma; Alisheke Mutemwa; Bernard M. Hang'ombe; Aaron S. Mweene; Ayato Takada; Chihiro Sugimoto; Yasuhiko Suzuki; Hiroshi Kida; Hirofumi Sawa
  INFECTION GENETICS AND EVOLUTION, 32, 143, 147, 2015年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• New Aspects of Collectin Functions
  Katsuki Ohtani; Yasuhiko Suzuki; Nobutaka Wakamiya
  Glycoscience: Biology and Medicine, 1029, 1036, Springer Japan, 2015年01月01日, ［査読有り］
  英語, 論文集(書籍)内論文
• Molecular identification of non-tuberculous mycobacteria isolated from clinical specimens in Zambia
  Grace Mwikuma; Geoffry Kwenda; Bernard M. Hang'ombe; Edgar Simulundu; Trevor Kaile; Selestine Nzala; Seter Siziya; Yasuhiko Suzuki
  ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS, 14, 1, 1, 2015年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Evaluation of Anti-TBGL Antibody in the Diagnosis of Tuberculosis Patients in China
  Jingge Zhao; Zhaoqin Zhu; Xiaoyan Zhang; Yasuhiko Suzuki; Haorile Chagan-Yasutan; Haili Chen; Yanmin Wan; Jianqing Xu; Yugo Ashino; Toshio Hattori
  JOURNAL OF IMMUNOLOGY RESEARCH, 2015, 834749, 834749, 2015年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Scavenger receptor CL-P1 mainly utilizes a collagen-like domain to uptake microbes and modified LDL
  Kenichiro Mori; Katsuki Ohtani; SeongJae Jang; YounUck Kim; Insu Hwang; Nitai Roy; Yasuyuki Matsuda; Yasuhiko Suzuki; Nobutaka Wakamiya
  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1840, 12, 3345, 3356, 2014年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Scavenger receptor CL-P1 mainly utilizes a collagen-like domain to uptake microbes and modified LDL.
  Kenichiro Mori; Katsuki Ohtani; SeongJae Jang; YounUck Kim; Insu Hwang; Nitai Roy; Yasuyuki Matsuda; Yasuhiko Suzuki; Nobutaka Wakamiya
  Biochimica et biophysica acta, 1840, 12, 3345, 56, 12, 2014年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Collectins are considered to play a role in host defense via complement activation and opsonization, and are composed of a collagen-like domain and a carbohydrate recognition domain (CRD). Collectin placenta 1 (CL-P1) showed scavenger receptor activity as functions in vitro, and has three candidate domains: a coiled-coil domain, a collagen-like domain and CRD. METHODS: We constructed seven types of CL-P1 deletion mutants to determine the site of each ligand binding domain, and observed whether the specific binding to sugar ligand, microbes, or oxidized LDL decreases or not in cells with CL-P1 deletion mutants and CL-P1 containing mutations of amino acid, respectively. RESULTS: CL-P1 mainly interacted with ligands of microbes through the collagen-like domain and it binds a sugar ligand through the CRD. Additionally it could bind oxidized low density lipoprotein (OxLDL) due to the coiled-coil domain as well as the collagen-like domain. This binding study using mutants at three positively charged sites in the collagen-like domain reveals that the site of R496 K499 K502 plays the most important role in ligand binding functions for microbes and OxLDL. CONCLUSIONS: CL-P1 has three unique functional domains: the collagen-like domain mainly acts against most negatively charged ligands, and the CRD specifically does against sugar substances, while the coiled-coil domain additionally acts on modified LDL. GENERAL SIGNIFICANCE: We considered that the binding activity for various ligands due to the association of a coiled-coil domain, a collagen-like domain and/or a CRD in CL-P1, might play a role in physiological functions in the animal body.
• Scavenger receptor CL-P1 mediates endocytosis by associating with AP-2 mu 2
  Jang SeongJae; Ohtani Katsuki; Fukuoh Atsushi; Mori Kenichiro; Yoshizaki Takayuki; Kitamoto Noritoshi; Kim YounUck; Suzuki Yasuhiko; Wakamiya Nobutaka
  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1840, 11, 3226, 3237, 2014年11月, ［査読有り］
• Scavenger receptor CL-P1 mediates endocytosis by associating with AP-2μ2.
  Jang S; Ohtani K; Fukuoh A; Mori K; Yoshizaki T; Kitamoto N; Kim Y; Suzuki Y; Wakamiya N
  Biochimica et biophysica acta, 1840, 11, 3226, 37, 11, 2014年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Scavenger receptor CL-P1 (collectin placenta 1) has been found recently as a first membrane-type collectin which is mainly expressed in vascular endothelial cells. CL-P1 can endocytose OxLDL as well as microbes but in general, the endocytosis mechanism of a scavenger receptor is not well elucidated. METHODS: We screened a placental cDNA library using a yeast two-hybrid system to detect molecules associated with the cytoplasmic domain of CL-P1. We analyzed the binding and endocytosis of several ligands in CL-P1 transfectants and performed the inhibition study using tyrphostin A23 which is a specific inhibitor of tyrosine kinase, especially in μ2-dependent endocytosis and the site-directed mutagenesis in the endocytosis YXXΦ motif in CL-P1 cytoplasmic region. Furthermore, the SiRNA study of clathrin, adaptor AP-2 and dynamin-2 during the endocytosis of OxLDL in CL-P1 transfectant cells was carried out. RESULTS: We identified μ2 subunit of the AP-2 adaptor complex as a molecule associated with the cytoplasmic region of CL-P1. We demonstrated that AP-2μ2 was essential for CL-P1 mediated endocytosis of OxLDL in CL-P1 transfectant cells and its endocytosis was also mediated by clathrin, dynamin and adaptin complex molecules. CONCLUSIONS: Tyrosine-based YXXΦ sequences play an important role in CL-P1-mediated OxLDL endocytosis associated with AP-2μ2. GENERAL SIGNIFICANCE: This might be the first finding of the clear endocytosis mechanism in scavenger receptor CL-P1.
• Dominant modern sublineages and a new modern sublineage of Mycobacterium tuberculosis Beijing family clinical isolates in Heilongjiang Province, China
  Di Li; Cai-Bo Dong; Jia-Yi Cui; Chie Nakajima; Chun-Lei Zhang; Xin-Ling Pan; Gao-Xiang Sun; En-Yu Dai; Yasuhiko Suzuki; Min Zhuang; Hong Ling
  INFECTION GENETICS AND EVOLUTION, 27, 294, 299, 2014年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• The Babesia bovis gene and promoter model: an update from full-length EST analysis.
  Yamagishi J; Wakaguri H; Yokoyama N; Yamashita R; Suzuki Y; Xuan X; Igarashi I
  BMC genomics, 15, 678, 2014年08月, ［査読有り］
• Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes
  Ryoyo Ikebuchi; Satoru Konnai; Tomohiro Okagawa; Kazumasa Yokoyama; Chie Nakajima; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  IMMUNOLOGY, 142, 4, 551, 561, 2014年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Antibiotic Resistance in Escherichia coli Isolated from Shrimps and Their Environment
  Kanjana Changkaew; Fuangfa Utrarachkij; Kanokrat Siripanichgon; Chie Nakajima; Orasa Suthienkul; Yasuhiko Suzuki
  JOURNAL OF FOOD PROTECTION, 77, 8, 1394, 1401, 2014年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Identification and characterization of bovine programmed death-ligand 2
  Asami Nishimori; Satoru Konnai; Ryoyo Ikebuchi; Tomohiro Okagawa; Chie Nakajima; Yasuhiko Suzuki; Claro N. Mingala; Shiro Murata; Kazuhiko Ohashi
  MICROBIOLOGY AND IMMUNOLOGY, 58, 7, 388, 397, 2014年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Functional analysis of the receptor binding domain of SARS coronavirus S1 region and its monoclonal antibody
  Hyun Kim; Yeongjin Hong; Keigo Shibayama; Yasuhiko Suzuki; Nobutaka Wakamiya; Youn Uck Kim
  GENES & GENOMICS, 36, 3, 387, 397, 2014年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Identification and Characterization of a Trypanosoma congolense 46 kDa Protein as a Candidate Serodiagnostic Antigen
  Mo Zhou; Keisuke Suganuma; Ngasaman Ruttayaporn; Thu-Thuy Nguyen; Shino Yamasaki; Ikuo Igarashi; Shin-ichiro Kawazu; Yasuhiko Suzuki; Noboru Inoue
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 6, 799, 806, 2014年06月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
  Maekawa N; Konnai S; Ikebuchi R; Okagawa T; Adachi M; Takagi S; Kagawa Y; Nakajima C; Suzuki Y; Murata S; Ohashi K
  PloS one, 9, 6, e98415, 2014年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
  Yasushi Itoh; Reiko Yoshida; Shintaro Shichinohe; Megumi Higuchi; Hirohito Ishigaki; Misako Nakayama; Van Loi Pham; Hideaki Ishida; Mitsutaka Kitano; Masahiko Arikata; Naoko Kitagawa; Yachiyo Mitsuishi; Kazumasa Ogasawara; Hideaki Tsuchiya; Takahiro Hiono; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Mutsumi Ito; Le Quynh Mai; Yoshihiro Kawaoka; Hiroko Miyamoto; Mari Ishijima; Manabu Igarashi; Yasuhiko Suzuki; Ayato Takada
  PLOS PATHOGENS, 10, 6, e1004192, 2014年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Molecular characterization of Mycobacterium tuberculosis isolates from elephants of Nepal.
  Paudel S; Mikota SK; Nakajima C; Gairhe KP; Maharjan B; Thapa J; Poudel A; Shimozuru M; Suzuki Y; Tsubota T
  Tuberculosis (Edinburgh, Scotland), 94, 3, 287, 292, 2014年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Diagnostic value of the recombinant tandem repeat antigen TeGM6-4r for surra in water buffaloes
  Thu-Thuy Nguyen; Mo Zhou; Ngasaman Ruttayaporn; Quoc Doanh Nguyen; Viet Khong Nguyen; Yasuyuki Goto; Yasuhiko Suzuki; Shin-ichiro Kawazu; Noboru Inoue
  VETERINARY PARASITOLOGY, 201, 1-2, 18, 23, 2014年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Bacterial Diversity in Sea Ice from the Southern Ocean and the Sea of Okhotsk
  Okubo, T; Tosaka, Y; Sato, T; Usui, M; Nakajima, C; Suzuki, Y; Imura, S; Tamura, Y
  Journal of Applied & Environmental Microbiology, 2, 6, 266, 272, 2014年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Elevated OPN, IP-10, and Neutrophilia in Loop-Mediated Isothermal Amplification Confirmed Tuberculosis Patients
  Beata Shiratori; Susan Leano; Chie Nakajima; Haorile Chagan-Yasutan; Toshiro Niki; Yugo Ashino; Yasuhiko Suzuki; Elisabeth Telan; Toshio Hattori
  MEDIATORS OF INFLAMMATION, 2014, 513263, 513263, 2014年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• What hansen’s disease research learned from tuberculosis research: From molecular biological aspect
  Yasuhiko Suzuki; Tomoyuki Yamaguchi; Hyun Kim; Kazumasa Yokoyama; Chie Nakajima
  Japanese Journal of Leprosy, 83, 3, 131, 137, Japanese Leprosy Association, 2014年, ［査読有り］, ［国内誌］
  日本語, 研究論文（学術雑誌）
• Intra-subspecies sequence variability of the MACPPE12 gene in Mycobacterium avium subsp hominissuis
  Tomotada Iwamoto; Kentaro Arikawa; Chie Nakajima; Noriko Nakanishi; Yukiko Nishiuchi; Shiomi Yoshida; Aki Tamaru; Yutaka Tamura; Yoshihiko Hoshino; Heekyung Yoo; Young Kil Park; Hajime Saito; Yasuhiko Suzuki
  INFECTION GENETICS AND EVOLUTION, 21, 479, 483, 2014年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Direct detection of Mycobacterium avium in environmental water and scale samples by loop-mediated isothermal amplification
  Yukiko Nishiuchi; Aki Tamaru; Yasuhiko Suzuki; Seigo Kitada; Ryoji Maekura; Yoshitaka Tateishi; Mamiko Niki; Hisashi Ogura; Sohkichi Matsumoto
  JOURNAL OF WATER AND HEALTH, 12, 2, 211, 219, 2014年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Expression, immunolocalization and serodiagnostic value of Tc38630 protein from Trypanosoma congolense
  Kennedy Miyoro Mochabo; Mo Zhou; Keisuke Suganuma; Shin-Ichiro Kawazu; Yasuhiko Suzuki; Noboru Inoue
  Parasitology Research, 112, 9, 3357, 3363, 2013年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Preliminary investigation of trypanosomosis in exotic dog breeds from Zambia’s Luangwa and Zambezi valleys using LAMP
  Namangala B; Oparaocha E; Kajino K; Hayashida K; Moonga L; Inoue N; Suzuki Y; Sugimoto C
  Am J Trop Med Hygine, 89, 1, 116, 118, 2013年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Tumor budding as a useful prognostic marker in T1-stage squamous cell carcinoma of the esophagus.
  Hitoshi Teramoto; Masahiko Koike; Chie Tanaka; Suguru Yamada; Goro Nakayama; Tsutomu Fujii; Hiroyuki Sugimoto; Michitaka Fujiwara; Yasuhiko Suzuki; Yasuhiro Kodera
  Journal of surgical oncology, 108, 1, 42, 6, 2013年07月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Establishing a new prognostic factor for early-stage cancer may seem difficult due to the small number of disease-specific deaths. Tumor budding has been recognized as a useful microscopic finding reflecting biological activity of the tumor. METHODS: Tumor budding stand for isolated single cancer cells and cell clusters scattered beyond the tumor margin at the invasive front. It was searched for in the resected esophagus with T1 squamous cell carcinoma (SCC), and the correlation between the tumor budding, patient survival, and various pathologic factors were analyzed to verify whether tumor budding is a prognostic factor in superficial esophageal cancer. RESULTS: Seventy-nine patients undergoing curative esophagectomy were assigned to frequent (n = 29) and rare (n = 50) groups according to the microscopically observed frequency of tumor budding in the tumor. Three-year survival rates after esophagectomy were 48.8% for the frequent group and 94.5% for the rare group. Multivariate analysis using the Cox proportional hazards model identified this morphological variable as a significant independent prognostic factor. CONCLUSIONS: Tumor budding reflects the biological activity of the tumor and may be a useful prognostic indicator even in early-stage SCC of esophagus.
• Whole-genome sequencing of Theileria parva strains provides insight into parasite migration and diversification in the African continent.
  Hayashida K; Abe T; Weir W; Nakao R; Ito K; Kajino K; Suzuki Y; Jongejan F; Geysen D; Sugimoto C
  DNA research : an international journal for rapid publication of reports on genes and genomes, 20, 3, 209, 220, 2013年06月, ［査読有り］
• Applicability of In-House Loop-Mediated Isothermal Amplification for Rapid Identification of Mycobacterium tuberculosis Complex Grown on Solid Media
  Benjawan Phetsuksiri; Janisara Rudeeaneksin; Sopa Srisungngam; Supranee Bunchoo; Dhanida Roienthong; Tetsu Mukai; Chie Nakajima; Shigeyuki Hamada; Yasuhiko Suzuki
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 66, 3, 249, 251, 2013年05月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Proposed vector candidate: Leptotrombidium palpale for Shimokoshi type Orientia tsutsugamushi.
  Seto J; Suzuki Y; Otani K; Qiu Y; Nakao R; Sugimoto C; Abiko C
  Microbiology and immunology, 57, 2, 111, 117, 2, 2013年02月, ［査読有り］
  英語
• Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro
  Ryoyo Ikebuchi; Satoru Konnai; Tomohiro Okagawa; Kazumasa Yokoyama; Chie Nakajima; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
  Veterinary Research, 44, 1, 59, 59, 1, 2013年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Simple multiplex PCR assay for identification of Beijing family Mycobacterium tuberculosis isolates with a lineage-specific mutation in Rv0679c
  Chie Nakajima; Aki Tamaru; Zeaur Rahim; Ajay Poudel; Bhagwan Maharjan; Khin Saw Aye; Hong Ling; Toshio Hattori; Tomotada Iwamoto; Yukari Fukushima; Haruka Suzuki; Yasuhiko Suzuki; Takashi Matsuba
  Journal of Clinical Microbiology, 51, 7, 2025, 2032, American Society for Microbiology, 2013年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of extensively drug-resistant Mycobacterium tuberculosis in Nepal
  Ajay Poudel; Bhagwan Maharjan; Chie Nakajima; Yukari Fukushima; Basu D. Pandey; Antje Beneke; Yasuhiko Suzuki
  TUBERCULOSIS, 93, 1, 84, 88, 2013年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Revisiting a medical case of "stinging" in the human oral cavity caused by ingestion of raw squid (Cephalopoda: Teuthida): new data on the functioning of squid's spermatophores
  Jose Eduardo A. R. Marian; Yukihiro Shiraki; Kumi Kawai; Sawako Kojima; Yasuhiko Suzuki; Kenzo Ono
  ZOOMORPHOLOGY, 131, 4, 293, 301, 2012年12月
  英語, 研究論文（学術雑誌）
• Molecular mechanism of rifampicin and isoniazid resistance in Mycobacterium tuberculosis from Bangladesh
  Zeaur Rahim; Chie Nakajima; Rubhana Raqib; Khalequ Zaman; Hubert P. Endtz; Adri G. M. van der Zanden; Yasuhiko Suzuki
  TUBERCULOSIS, 92, 6, 529, 534, 2012年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Mycobacterium bovis infection at the interface between domestic and wild animals in Zambia
  Mudenda B. Hang'ombe; Musso Munyeme; Chie Nakajima; Yukari Fukushima; Haruka Suzuki; Wigganson Matandiko; Akihiro Ishii; Aaron S. Mweene; Yasuhiko Suzuki
  BMC VETERINARY RESEARCH, 8, 221, 221, 2012年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity
  Peter S. Lee; Reiko Yoshida; Damian C. Ekiert; Naoki Sakai; Yasuhiko Suzuki; Ayato Takada; Ian A. Wilson
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109, 42, 17040, 17045, 2012年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Impact of Amino Acid Substitutions in B Subunit of DNA Gyrase in Mycobacterium leprae on Fluoroquinolone Resistance
  Kazumasa Yokoyama; Hyun Kim; Tetsu Mukai; Masanori Matsuoka; Chie Nakajima; Yasuhiko Suzuki
  PLoS Neglected Tropical Diseases, 6, 10, e1838, 10, 2012年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Impact of Amino Acid Substitutions in B Subunit of DNA Gyrase in Mycobacterium leprae on Fluoroquinolone Resistance
  Kazumasa Yokoyama; Hyun Kim; Tetsu Mukai; Masanori Matsuoka; Chie Nakajima; Yasuhiko Suzuki
  PLOS NEGLECTED TROPICAL DISEASES, 6, 10, 2012年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Pulmonary tuberculosis in patients with diabetes mellitus in Bangladesh
  Zeaur Rahim; Mst. Sabiha Banu Momi; Sajal K. Saha; K. Zaman; Khwaja Nazim Uddin; S. N. A. Ashraf Jamil; Nazmun Nahar; A. K. Azad Khan; E. A. W. D. Cooreman; Motiuddin Ahmed; A. G. M. van der Zanden; Chie Nakajima; Yasuhiko Suzuki
  INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, 16, 8, 1132, 1133, 2012年08月, ［査読有り］, ［国際誌］
  英語
• Dominant Incidence of Multidrug and Extensively Drug-Resistant Specific Mycobacterium tuberculosis Clones in Osaka Prefecture, Japan
  Aki Tamaru; Chie Nakajima; Takayuki Wada; Yajun Wang; Manabu Inoue; Ryuji Kawahara; Ryoji Maekura; Yuriko Ozeki; Hisashi Ogura; Kazuo Kobayashi; Yasuhiko Suzuki; Sohkichi Matsumoto
  PLOS ONE, 7, 8, e42505, 2012年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Rapid Identification of Mycobacterium tuberculosis in BACTEC MGIT960 Cultures by In-House Loop-Medicated Isothermal Amplification
  Janisara Rudeeaneksin; Supranee Bunchoo; Sopa Srisungngam; Pathom Sawanpanyalert; Sawet Chamnangrom; Atipa Kamolwat; Porntip Thanasripakdeekul; Tooru Taniguchi; Chie Nakajima; Yasuhiko Suzuki; Benjawan Phetsuksiri
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 65, 4, 306, 311, 2012年07月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Genetic diversity of Mycobacterium avium subsp hominissuis strains isolated from humans, pigs, and human living environment
  Tomotada Iwamoto; Chie Nakajima; Yukiko Nishiuchi; Tomoko Kato; Shiomi Yoshida; Noriko Nakanishi; Aki Tamaru; Yutaka Tamura; Yasuhiko Suzuki; Masao Nasu
  INFECTION GENETICS AND EVOLUTION, 12, 4, 846, 852, 2012年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A New Loop-Mediated Isothermal Amplification Method for Rapid, Simple, and Sensitive Detection of Leptospira spp. in Urine
  Nobuo Koizumi; Chie Nakajima; Tsunehito Harunari; Tsutomu Tanikawa; Toshihiro Tokiwa; Eriko Uchimura; Tokujiro Furuya; Claro Niegos Mingala; Marvin Ardeza Villanueva; Makoto Ohnishi; Yasuhiko Suzuki
  JOURNAL OF CLINICAL MICROBIOLOGY, 50, 6, 2072, 2074, 2012年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Quinolone-Induced Upregulation of Osteopontin Gene Promoter Activity in Human Lung Epithelial Cell Line A549
  Beata Shiratori; Jing Zhang; Osamu Usami; Haorile Chagan-Yasutan; Yasuhiko Suzuki; Chie Nakajima; Toshimitsu Uede; Toshio Hattori
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56, 6, 2868, 2872, 2012年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal
  Ajay Poudel; Chie Nakajima; Yukari Fukushima; Haruka Suzuki; Basu Dev Pandey; Bhagwan Maharjan; Yasuhiko Suzuki
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56, 6, 2831, 2836, 2012年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance
  Yasuhiko Suzuki; Chie Nakajima; Aki Tamaru; Hyun Kim; Takashi Matsuba; Hajime Saito
  INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 39, 5, 435, 439, 2012年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A Rapid Loop-Mediated Isothermal Amplification Assay Targeting hspX for the Detection of Mycobacterium tuberculosis Complex
  Aixiao Bi; Chie Nakajima; Yukari Fukushima; Aki Tamaru; Isamu Sugawara; Akio Kimura; Ryuji Kawahara; Zhongyi Hu; Yasuhiko Suzuki
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 65, 3, 247, 251, 2012年05月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Distinct Clinical Features in Nontuberculous Mycobacterial Disease with or without Latent Tuberculosis Infection
  Umme Ruman Siddiqi; Haorile Chagan-Yasutan; Chie Nakajima; Hiroki Saitoh; Yugo Ashino; Osamu Usami; Beata Shiratori; Motoki Usuzawa; Yasuhiko Suzuki; Toshio Hattori
  TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 226, 4, 313, 319, 2012年04月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
  Andrea Marzi; Reiko Yoshida; Hiroko Miyamoto; Mari Ishijima; Yasuhiko Suzuki; Megumi Higuchi; Yukie Matsuyama; Manabu Igarashi; Eri Nakayama; Makoto Kuroda; Masayuki Saijo; Friederike Feldmann; Douglas Brining; Heinz Feldmann; Ayato Takada
  PLOS ONE, 7, 4, e36192, 2012年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Possible horizontal transmission of Salmonella via reusable egg trays in Thailand
  Fuangfa Utrarachkij; Srirat Pornraungwong; Kanokrat Siripanichgon; Chie Nakajima; Yasuhiko Suzuki; Orasa Suthienkul
  INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY, 154, 1-2, 73, 78, 2012年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Amino Acid Substitutions at Position 95 in GyrA Can Add Fluoroquinolone Resistance to Mycobacterium leprae
  Kazumasa Yokoyama; Hyun Kim; Tetsu Mukai; Masanori Matsuoka; Chie Nakajima; Yasuhiko Suzuki
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56, 2, 697, 702, 2012年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Characterization of Toxoplasma gondii 5’ UTR with encyclopedic TSS information
  Yamagishi J; Watanabe J; Goo YK; Masatani T; Suzuki Y; Xuan X
  The Journal of Parasitology, 98, 2, 445, 447, American Society of Parasitologists, 2012年02月, ［査読有り］
  英語, 研究論文（学術雑誌）, The 5′ UTR is widely involved in gene expression via post-transcriptional regulation. However, a detailed profile of the 5′ UTR for Toxoplasma gondii has not yet been demonstrated. To investigate the issue, we compared the predicted open reading frames (ORFs) and transcription start sites (TSSs) of T. gondii obtained by TSS-seq, a method that enables analysis of encyclopedic TSSs with next-generation sequencers. As a result, it was demonstrated that the mode length of the 5′ UTR is between 120 and 140 nucleotides (nts) when a subset of genes with predicted signal peptides was examined. However, when genes without the signal peptide were examined, the length was extended to approximately 600 nts. Because additional information on the predicted signal peptide generates increased reliability to the 5′ end estimation of each ORF, we believe that the former value was more reliable as a representative of the 5′ UTR length of T. gondii. The discrepancy suggests that current predictions of the 5′ end of the ORF were less accurate and considerably more discordant with the natural status. The 5′ untranslated region (5′ UTR) is defined as that between the 5′ end of the transcripts and just in front of a start codon of an ORF. Therefore, the 5′ UTR does not contain any information for a protein sequence; however, it is involved in the control of protein expression via the modulation of translational efficiency (Kozak, 1991b; Hughes, 2006).http://www.journalofparasitology.org/doi/abs/10.1645/GE-2864.1
• Comparison of human blood concentrations of collectin kidney 1 and mannan-binding lectin
  Takayuki Yoshizaki; Katsuki Ohtani; Wataru Motomura; Seong-Jae Jang; Ken-ichiro Mori; Noritoshi Kitamoto; Itsuro Yoshida; Yasuhiko Suzuki; Nobutaka Wakamiya
  JOURNAL OF BIOCHEMISTRY, 151, 1, 57, 64, 2012年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Influence of Lineage-Specific Amino Acid Dimorphisms in GyrA on Mycobacterium tuberculosis Resistance to Fluoroquinolones
  Hyun Kim; Chie Nakajima; Youn Uck Kim; Kazumasa Yokoyama; Yasuhiko Suzuki
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 65, 1, 72, 74, 2012年01月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Frequent Detection of Anti-Tubercular-Glycolipid-IgG and -IgA Antibodies in Healthcare Workers with Latent Tuberculosis Infection in the Philippines
  Umme Ruman Siddiqi; Prisca Susan A. Leano; Haorile Chagan-Yasutan; Beata Shiratori; Hiroki Saitoh; Yugo Ashino; Yasuhiko Suzuki; Toshio Hattori; Elizabeth Freda O. Telan
  CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2012, 610707, 610707, 2012年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Biological Functions of the Novel Collectins CL-L1, CL-K1, and CL-P1
  Katsuki Ohtani; Yasuhiko Suzuki; Nobutaka Wakamiya
  JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2012, 493945, 493945, 2012年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of theileria-induced leukocyte transformation
  Hayashida K; Hara Y; Abe T; Chisato Yamasaki C.Y; Toyoda A; Kosuge T; Suzuki Y; Sato Y; Kawashima S; Katayama T; Wakaguri H; Noboru Inoue N.I; Keiichi Homma K.H; Tada-Umezaki M; Yagi Y; Yasuyuki Fujii Y.F; Takuya Habara T.H; Kanehisa M; Hidemi Watanabe H; W; Ito K; Gojobori T; Hideaki Sugawara H.S; Imanishi T; Weir W; Gardner M; Arnab Pain A; P; Shiels B; Hattori M; Nene V; Sugimoto C
  mBio, 3, 5, 2012年, ［査読有り］
• Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1.
  Mitsuko Fukuda; Katsuki Ohtani; Seong-Jae Jang; Takayuki Yoshizaki; Ken-Ichiro Mori; Wataru Motomura; Itsuro Yoshida; Yasuhiko Suzuki; Yutaka Kohgo; Nobutaka Wakamiya
  Biochimica et biophysica acta, 1810, 12, 1150, 9, 12, 2011年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Scavenger receptors are generally expressed in macrophages and vascular endothelial cells and some scavenger receptors are thought to contribute to the development of atherosclerosis. METHODS: We cloned the cDNA of a zebrafish CL-P1 (collectin placenta 1) and performed a knockdown study using its antisense morpholino oligonucleotides (MO). RESULTS: Zebrafish CL-P1 (zCL-P1) is 51% identical to human CL-P1 in its amino acid sequence. Microbes and OxLDL bound to zCL-P1 cDNA transfected cells. zCL-P1 mRNA expression gradually increased after 6hours post-fertilization (hpf), reached its highest level at 24hpf, and then decreased, which is similar to the gene expression pattern of Tie-2. The knockdown of zCL-P1 led to an increase in the number of zebrafish embryos with severe morphological abnormalities such as short body lengths and defects in the dorsal aorta at 48hpf. Simultaneous injection of both MO and synthetic zCL-P1 or zVEGF mRNA rescued the abnormal phenotype. CONCLUSIONS: In vivo knockdown study shows that zCL-P1 is implicated in vasculogenesis and those of our in vitro study support its role as a scavenger receptor. GENERAL SIGNIFICANCE: These results suggest that zCL-P1 might be essential for vasculogenesis during the early embryonic phase in bone fish.
• Stinging in the oral cavity caused by ingestion of the sperm bags of a squid: a case report.
  Yukihiro Shiraki; Kumi Kawai; Sawako Kojima; Yasuhiko Suzuki; Kenzo Ono
  Pathology international, 61, 12, 749, 51, 2011年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, We present a case of stinging in the oral cavity caused by ingestion of the sperm bags of a squid. The patient experienced severe pain in her oral cavity immediately after eating raw squid. When she was examined at our hospital, we found that several small whitish spindle-shaped stings were stuck to the mucous membrane of the hard palate. A biopsy was performed, and the whitish stings were removed as well. We also performed a histological examination of the remaining part of the raw squid brought by the patient. The biopsy showed that the sperm bags of the squid had thrust into the squamous epithelium of the patient. The remaining part of the raw squid consisted of the testis and the sperm bags. After removal of all stings, the pain reduced, and the wound healed in due course. Larva migrans and anisakiasis are infections known to be caused by consumption of raw seafood. Although the condition reported here is relatively rare, doctors should also keep this condition in mind for patients reporting pain after eating raw seafood.
• Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1
  Fukuda Mitsuko; Ohtani Katsuki; Jang Seong-Jae; Yoshizaki Takayuki; Mori Ken-ichiro; Motomura Wataru; Yoshida Itsuro; Suzuki Yasuhiko; Kohgo Yutaka; Wakamiya Nobutaka
  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1810, 12, 1150, 1159, 2011年12月, ［査読有り］
• The induction of human CL-P1 expression in hypoxia/reoxygenation culture condition and rat CL-P1 after ischemic/reperfusion treatment.
  Satoshi Koyama; Katsuki Ohtani; Jun Fukuzawa; Naoyuki Yao; Mitsuko Fukuda; Seong-Jae Jang; Naoyuki Hasebe; Kenjiro Kikuchi; Hiroyuki Itabe; Itsuro Yoshida; Yasuhiko Suzuki; Nobutaka Wakamiya
  Biochimica et biophysica acta, 1810, 9, 836, 42, 9, 2011年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Oxidative stress-induced endothelial dysfunction and oxidized low-density lipoprotein (LDL) might play a key role in the pathogenesis of atherosclerosis. We recently identified a vascular endothelial scavenger receptor, collectin placenta 1 (CL-P1), which acts as a receptor for oxidized LDL as well as for microbes. METHODS: We demonstrate how hypoxic and oxidative stress induced CL-P1 expression and compared their effects with the expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), an endothelial scavenger receptor expressed by oxidative stress. RESULTS: Hypoxia/reoxygenation induced CL-P1 mRNA and protein expression in human umbilical vein endothelial cells (HUVECs). The expression of LOX-1 mRNA in these cells peaked slightly at 24 h, while the expression of CL-P1 had an onset at 72 h and was sustained for 120 h after reoxygenation. Furthermore, the exposure of rat carotid artery endothelium to ischemia/reperfusion increased the maximal CL-P1 mRNA expression at 72 h and expression of its protein peaked at 7 days after this treatment. We demonstrate that CL-P1 up-regulation is induced in vitro and in vivo by oxidative stress. GENERAL SIGNIFICANCE: The inducible expression of CL-P1 by oxidative stress might play a crucial role in endothelial dysfunction or chronic activation leading to the pathogenesis of atherosclerosis.
• The induction of human CL-P1 expression in hypoxia/reoxygenation culture condition and rat CL-P1 after ischemic/reperfusion treatment
  Satoshi Koyama; Katsuki Ohtani; Jun Fukuzawa; Naoyuki Yao; Mitsuko Fukuda; Seong-Jae Jang; Naoyuki Hasebe; Kenjiro Kikuchi; Hiroyuki Itabe; Itsuro Yoshida; Yasuhiko Suzuki; Nobutaka Wakamiya
  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1810, 9, 836, 842, 2011年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Impact of the E540V Amino Acid Substitution in GyrB of Mycobacterium tuberculosis on Quinolone Resistance
  Hyun Kim; Chie Nakajima; Kazumasa Yokoyama; Zeaur Rahim; Youn Uck Kim; Hiroki Oguri; Yasuhiko Suzuki
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55, 8, 3661, 3667, 2011年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A case of autoimmune hepatitis with Graves' disease treated by propylthiouracil.
  Ikuko Sato; Taku Tsunekawa; Yuri Shinohara; Yuichiro Nishio; Yuko Shimizu; Yasuhiko Suzuki; Shuko Yoshioka
  Nagoya journal of medical science, 73, 3-4, 205, 9, 2011年08月, ［国内誌］
  英語, 研究論文（学術雑誌）, A 58-year-old woman was referred to our hospital because of liver dysfunction. Her serum levels of AST (619 IU/l) and ALT (603 IU/l) had increased. Histological findings in the liver biopsy were compatible to autoimmune hepatitis (AIH), and the diagnosis of AIH was confirmed by the diagnostic criteria. She was admitted to a nearby hospital 3 years ago, and diagnosed with Graves' disease. She received methimazole (MMI) at first, which was discontinued due to liver injury in one month, then propylthiouracil (PTU) was administered. One year later, transaminase increased and was decreased by stopping PTU administration. PTU was restarted after her transaminase decreased, but a recurrence of hepatotoxicity was observed, and she was referred to our hospital. Oral prednisolone decreased liver function immediately. In this case, PTU-induced liver injury was suspected as a possible trigger of AIH. While PTU remains a commonly used drug in the treatment of hyperthyroidism, severe liver injury is reported in some cases. If liver injury is observed in patients treated with PTU, rechallenge is not recommended in order to avoid severe hepatotoxicity.
• Involvement of TRP channels in the signal transduction of bradykinin in human osteoblasts.
  Yasuhiko Suzuki; Daisuke Kodama; Shigemi Goto; Akifumi Togari
  Biochemical and biophysical research communications, 410, 2, 317, 21, 2011年07月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Bradykinin (BK), a mediator of pain and inflammation, is involved in bone metabolism. We have previously reported that BK increased the synthesis of interleukin-6 and prostaglandin E(2) via phosphorylation of ERK1/2 in human osteoblasts, SaM-1. In the present study, we investigated the signal transduction pathway of BK focusing on intracellular Ca(2+) kinetics in SaM-1 cells. Bath-applied BK increased intracellular Ca(2+) concentration through the activation of B(2) receptors. Removal of extracellular Ca(2+) attenuated the effects of BK. Additionally, thapsigargin, endoplasmic reticulum Ca(2+) pump inhibitor, completely inhibited BK-induced increase of intracellular Ca(2+). These results suggested that bath-applied BK activated store-operated Ca(2+) channels (SOCCs) following Ca(2+) store depletion via B(2) receptor. Although the molecular components of SOCCs have yet to be conclusively identified in all cell types, recent studies demonstrated that transient receptor potential canonical (TRPC) channels are candidates for them. TRPC1, TRPC3, TRPC4 and TRPC6 were expressed in SaM-1 cells and inhibitors of TRP channel, 2-aminoethoxydiphenyl borate, GdCl(3), LaCl(3) and flufenamic acid, inhibited the effects of BK. These findings suggested that BK activated SOCCs and induced Ca(2+) influx via B(2) receptor in human osteoblasts. Molecular components of the SOCCs are suggested to be TRPC channels.
• Gene regulation function of the three specificity protein-1 (Sp1) within the human collectin placenta-1 proximal promoter
  Youn Uck Kim; Katsuki Ohtani; Kenichiro Mori; Seong Jae Jang; Yasuhiko Suzuki; Nobutaka Wakamiya
  GENES & GENOMICS, 33, 3, 273, 281, 2011年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Genotypes and Characteristics of Clustering and Drug Susceptibility of Mycobacterium tuberculosis Isolates Collected in Heilongjiang Province, China
  Juan Wang; Yan Liu; Chun-Lei Zhang; Bin-Ying Ji; Liu-Zhuo Zhang; Yong-Zhen Shao; Shui-Lian Jiang; Yasuhiko Suzuki; Chie Nakajima; Chang-Long Fan; Yuan-Ping Ma; Geng-Wen Tian; Toshio Hattori; Hong Ling
  JOURNAL OF CLINICAL MICROBIOLOGY, 49, 4, 1354, 1362, 2011年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Rapid detection of Mycobacterium tuberculosis complex in Cattle and Lechwe (Kobus leche kafuensis) at the slaughter house.
  Hang’ombe M B; Nakajima C; Ishii A; Fukushima Y; Munyeme M; Matandiko W; Mweene A S; Suzuki Y
  Vet. Sci. Dev., 1, e5, 2011年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Possible Mode of Emergence for Drug-Resistant Leprosy Is Revealed by an Analysis of Samples from Mexico
  Masanori Matsuoka; Yasuhiko Suzuki; Iris Estrada Garcia; Mary Fafutis-Morris; Alberto Vargas-Gonzalez; Cristina Carreno-Martinez; Yukari Fukushima; Clue Nakajima
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 63, 6, 412, 416, 2010年11月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Occurrence and Molecular Characteristics of Methicillin-Resistant Staphylococcus aureus and Methicillin-Resistant Staphylococcus pseudintermedius in an Academic Veterinary Hospital
  Kanako Ishihara; Natsumi Shimokubo; Akie Sakagami; Hiroshi Ueno; Yasukazu Muramatsu; Tsuyoshi Kadosawa; Chie Yanagisawa; Hideaki Hanaki; Chie Nakajima; Yasuhiko Suzuki; Yutaka Tamura
  APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 76, 15, 5165, 5174, 2010年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A Novel Method for the Purification of DNA by Capturing Nucleic Acid and Magnesium Complexes on Non-Woven Fabric Filters under Alkaline Conditions for the Gene Diagnosis of Tuberculosis by Loop-Mediated Isothermal Amplification (LAMP)
  Tadashi Fukasawa; Naozumi Oda; Yasunao Wada; Aki Tamaru; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 63, 4, 246, 250, 2010年07月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Identification of Mycobacterium tuberculosis clinical isolates in Bangladesh by a species distinguishable multiplex PCR
  Chie Nakajima; Zeaur Rahim; Yukari Fukushima; Isamu Sugawara; Adri G. M. van der Zanden; Aki Tamaru; Yasuhiko Suzuki
  BMC INFECTIOUS DISEASES, 10, 118, 118, 2010年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• A rapid, simple, and sensitive loop-mediated isothermal amplification method to detect toxigenic Vibrio cholerae in rectal swab samples
  Kazuhisa Okada; Siriporn Chantaroj; Tooru Taniguchi; Yasuhiko Suzuki; Amonrattana Roobthaisong; Orapim Puiprom; Takeshi Honda; Pathom Sawanpanyalert
  DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 66, 2, 135, 139, 2010年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Development of novel humanized anti-CD20 antibodies based on affinity constant and epitope
  Susumu Uchiyama; Yasuhiko Suzuki; Kentaro Otake; Masami Yokoyama; Mitsuo Ohta; Shuichi Aikawa; Midori Komatsu; Tetsuji Sawada; Yoshitoyo Kagami; Yasuo Morishima; Kiichi Fukui
  CANCER SCIENCE, 101, 1, 201, 209, 2010年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Application of a Modified Loop-Mediated Isothermal Amplification Kit for Detecting Norovirus Genogroups I and II
  Tomoko Yoda; Yasuhiko Suzuki; Kenji Yamazaki; Naomi Sakon; Masashi Kanki; Tetsuo Kase; Kazuo Takahashi; Kiyoshi Inoue
  JOURNAL OF MEDICAL VIROLOGY, 81, 12, 2072, 2078, 2009年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Expression balances of structural genes in shikimate and flavonoid biosynthesis cause a difference in proanthocyanidin accumulation in persimmon (Diospyros kaki Thunb.) fruit.
  Takashi Akagi; Ayako Ikegami; Yasuhiko Suzuki; Junya Yoshida; Masahiko Yamada; Akihiko Sato; Keizo Yonemori
  Planta, 230, 5, 899, 915, 2009年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, Persimmon fruits accumulate a large amount of proanthocyanidin (PA) during development. Fruits of pollination-constant and non-astringent (PCNA) type mutants lose their ability to produce PA at an early stage of fruit development, while fruits of the normal (non-PCNA) type remain rich in PA until fully ripened. To understand the molecular mechanism for this difference, we isolated the genes involved in PA accumulation that are differentially expressed between PCNA and non-PCNA, and confirmed their correlation with PA content and composition. The expression of structural genes of the shikimate and flavonoid biosynthetic pathways and genes encoding transferases homologous to those involved in the accumulation of phenolic compounds were downregulated coincidentally only in the PCNA type. Analysis of PA composition using the phloroglucinol method suggested that the amounts of epigallocatechin and its 3-O-gallate form were remarkably low in the PCNA type. In the PCNA type, the genes encoding flavonoid 3'5' hydroxylase (F3'5'H) and anthocyanidin reductase (ANR) for epigallocatechin biosynthesis showed remarkable downregulation, despite the continuous expression level of their competitive genes, flavonoid 3' hydroxylation (F3'H) and leucoanthocyanidin reductase (LAR). We also confirmed that the relative expression levels of F3'5'H to F3'H, and ANR to LAR, were considerably higher, and the PA composition corresponded to the seasonal expression balances in both types. These results suggest that expressions of F3'5'H and ANR are important for PA accumulation in persimmon fruit. Lastly, we tested enzymatic activity of recombinant DkANR in vitro, which is thought to be an important enzyme for PA accumulation in persimmon fruits.
• Loop-Mediated Isothermal Amplification (LAMP) for the Direct Detection of Human Pulmonary Infections with Environmental (Nontuberculosis) Mycobacteria
  Bal Ram Adhikari; Basu Dev Pandey; Prakash Ghimire; Bhawana Shrestha; Manoj Khadka; Tomoko Yoda; Yasuhiko Suzuki
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 62, 3, 212, 214, 2009年05月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Regulator of complement activation (RCA) gene cluster in Xenopus tropicalis.
  Oshiumi H; Suzuki Y; Matsumoto M; Seya T
  Immunogenetics, 61, 5, 371, 384, 2009年05月, ［査読有り］
• Clinical profiling and use of loop-mediated isothermal amplification assay for rapid detection of Mycobacterium tuberculosis from sputum
  Ajay Poudel; B. D. Pandey; B. Lekhak; B. Rijal; B. R. Sapkota; Y. Suzuki
  Kathmandu University Medical Journal, 7, 26, 109, 114, 2009年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Epithelial inclusion cyst arising in an intramammary lymph node: case report with cytologic findings.
  Masato Nakaguro; Yasuhiko Suzuki; Shu Ichihara; Tadao K Kobayashi; Kenzo Ono
  Diagnostic cytopathology, 37, 3, 199, 202, 2009年03月, ［国際誌］
  英語, 研究論文（学術雑誌）, The occurrence of epithelial inclusion cysts (EIC) in axillary lymph nodes is a rare but well recognized entity, arising either from direct implantation or from embryonal rests. Theoretically, EIC can occur in intramammary lymph nodes, but there has been only one prior report of such a lesion. Here, we describe a case of an EIC arising in an intramammary lymph node of a 37-year-old woman. This report focuses on the FNA cytologic features of this lesion and its differential diagnoses. On FNA, the EIC arising in an intramammary lymph node was characterized by mature lymphocytes, squamous epithelial cells, and keratinizing material. The presence of squamous cells can lead to the erroneous diagnosis of more common breast lesions, such as squamous cell carcinoma or metaplastic carcinoma. Contrary to these more sinister diagnoses, EIC arising in an intramammary lymph node is a benign condition. As this rare lesion sometimes mimics a neoplasm both clinically and radiographically, awareness of this entity is important to prevent over treatment.
• Scavenger Receptor Collectin Placenta 1 (CL-P1) Predominantly Mediates Zymosan Phagocytosis by Human Vascular Endothelial Cells
  SeongJae Jang; Katsuki Ohtani; Atsushi Fukuoh; Takayuki Yoshizaki; Mitsuko Fukuda; Wataru Motomura; Kenichiro Mori; Jun Fukuzawa; Noritoshi Kitamoto; Itsuro Yoshida; Yasuhiko Suzuki; Nobutaka Wakamiya
  JOURNAL OF BIOLOGICAL CHEMISTRY, 284, 6, 3956, 3965, 2009年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Detection of culturable and nonculturable Legionella species from hot water systems of public buildings in Japan
  A. Edagawa; A. Kimura; H. Doi; H. Tanaka; K. Tomioka; K. Sakabe; C. Nakajima; Y. Suzuki
  JOURNAL OF APPLIED MICROBIOLOGY, 105, 6, 2104, 2114, 2008年12月
  英語, 研究論文（学術雑誌）
• A novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries
  Masanori Matsuoka; Khin Saw Aye; Kyaw Kyaw; Esterlina Virtudes Tan; Ma Victoria Balagon; Paul Saunderson; Robert Gelber; Masanao Makino; Chie Nakajima; Yasuhiko Suzuki
  JOURNAL OF MEDICAL MICROBIOLOGY, 57, 10, 1213, 1219, 2008年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Development of an in-house loop-mediated isothermal amplification (LAMP) assay for detection of Mycobacterium tuberculosis and evaluation in sputum samples of Nepalese patients
  Basu Dev Pandey; Ajay Poudel; Tomoko Yoda; Aki Tamaru; Naozumi Oda; Yukari Fukushima; Binod Lekhak; Basista Risal; Bishnu Acharya; Bishwa Sapkota; Chie Nakajima; Tooru Taniguchi; Benjawan Phetsuksiri; Yasuhiko Suzuki
  JOURNAL OF MEDICAL MICROBIOLOGY, 57, 4, 439, 443, 2008年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Immunolocalization of a novel collectin CL-K1 in murine tissues
  Wataru Motomura; Takayuki Yoshizaki; Katsuki Ohtani; Toshikatsu Okumura; Mituko Fukuda; Jun Fukuzawa; Kenichiro Mori; Seong-Jae Jang; Naoki Nomura; Itsuro Yoshida; Yasuhiko Suzuki; Yutaka Kohgo; Nobutaka Wakamiya
  JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 56, 3, 243, 252, 2008年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily
  Megumi Higuchi; Aya Matsuo; Masashi Shingai; Kyoko Shida; Akihiro Ishii; Kenji Funami; Yasuhiko Suzuki; Hiroyuki Oshiumi; Misako Matsumoto; Tsukasa Seya
  DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, 32, 2, 147, 155, 2008年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Streptococcus mutans由来sucrose phosphorylaseの熱安定性に関する研究
  高本 鉄兵; 深田 はるみ; 久保 亜希子; 鈴木 定彦; 北村 進一
  Journal of Applied Glycoscience Supplement, 2008, 108, 108, 日本応用糖質科学会, 2008年
  日本語
• Recombinant interleukin-12 and interleukin-18 antitumor therapy in a guinea-pig hepatoma cell implant model
  Ikuo Shiratori; Yasuhiko Suzuki; Hiroyuki Oshiumi; Nasim A. Begum; Takashi Ebihara; Misako Matsumoto; Kaoru Hazeki; Ken Kodama; Yasuo Kashiwazaki; Tsukasa Seya
  CANCER SCIENCE, 98, 12, 1936, 1942, 2007年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• The quail and chicken intestine have sialyl-galactose sugar chains responsible for the binding of influenza A viruses to human type receptors.
  Guo CT; Takahashi N; Yagi H; Kato K; Takahashi T; Yi SQ; Chen Y; Ito T; Otsuki K; Kida H; Kawaoka Y; Hidari KI; Miyamoto D; Suzuki T; Suzuki Y
  Glycobiology, 17, 7, 713, 24, 2007年07月, ［査読有り］, ［国際誌］
  英語, The receptor specificity of influenza viruses is one factor that allows avian influenza viruses to cross the species barrier. The recent transmissions of avian H5N1 and H9N2 influenza viruses from chickens and/or quails to humans indicate that avian influenza viruses can directly infect humans without an intermediate host, such as pigs. In this study, we used two strains of influenza A virus (A/PR/8/34, which preferentially binds to an avian-type receptor, and A/Memphis/1/71, which preferentially binds to a human-type receptor) to probe the receptor specificities in host cells. Epithelial cells of both quail and chicken intestines (colons) could bind both avian- and human-type viruses. Infected cultured quail colon cells expressed viral protein and allowed replication of the virus strain A/PR/8/34 or A/Memphis/1/71. To understand the molecular basis of these phenomena, we further investigated the abundance of sialic acid (Sia) linked to galactose (Gal) by the alpha2-3 linkage (Siaalpha2-3Gal) and Siaalpha2-6Gal in host cells. In glycoprotein and glycolipid fractions from quail and chicken colon epithelial cells, there were some bound components of Sia-Gal linkage-specific lectins, Maackia amurensis agglutinin (specific for Siaalpha2-3 Gal) and Sambucus nigra agglutinin (specific for Siaalpha2-6Gal), indicating that both Siaalpha2-3Gal and Siaalpha2-6Gal exist in quail and chicken colon cells. Furthermore, we demonstrated by fluorescence high-performance liquid chromatography (HPLC) analysis that 5-N-acetylneuraminic acid was the main molecular species of Sia, and we demonstrated by multi-dimensional HPLC mapping and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis that bi-antennary complex-type glycans alpha2-6 sialylated at the terminal Gal residue(s) are major (more than 79%) sialyl N-glycans expressed by intestinal epithelial tissues in both the chicken and quail. Taken together, these results indicate that quails and chickens have molecular characterization as potential intermediate hosts for avian influenza virus transmission to humans and could generate new influenza viruses with pandemic potential.
• Intracranial lesion of Erdheim-Chester disease.
  Satoko Shimada; Kenzo Ono; Yoshio Hashizume; Masato Nakaguro; Yasuhiko Suzuki; Naoyoshi Mori
  Human pathology, 38, 6, 950, 1, 2007年06月, ［国際誌］
  英語
• Tumor prone phenotype of mice deficient in a novel apoptosis-inducing gene, drs
  Yukihiro Tambe; Atsuko Yoshioka-Yamashita; Ken-ichi Mukaisho; Seiki Haraguchi; Tokuhiro Chano; Takahiro Isono; Takao Kawai; Yasuhiko Suzuki; Ryoji Kushima; Takanori Hattori; Motohito Goto; Shuichi Yamada; Makoto Kiso; Yumiko Saga; Hirokazu Inoue
  CARCINOGENESIS, 28, 4, 777, 784, 2007年04月, ［国際誌］
  英語, 研究論文（学術雑誌）
• Association of the Rv0679c protein with lipids and carbohydrates in Mycobacterium tuberculosis/Mycobacterium bovis BCG
  Takashi Matsuba; Yasuhiko Suzuki; Yoshinori Tanaka
  ARCHIVES OF MICROBIOLOGY, 187, 4, 297, 311, 2007年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Evaluation and application of reverse transcription loop-mediated isothermal amplification for detection of noroviruses
  Tomoko Yoda; Yasuhiko Suzuki; Kenji Yamazaki; Naomi Sakon; Masashi Kanki; Ikuko Aoyama; Teizo Tsukamoto
  JOURNAL OF MEDICAL VIROLOGY, 79, 3, 326, 334, 2007年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria
  Susumu Okamoto; Aki Tamaru; Chie Nakajima; Kenji Nishimura; Yukinori Tanaka; Shinji Tokuyama; Yasuhiko Suzuki; Kozo Ochi
  MOLECULAR MICROBIOLOGY, 63, 4, 1096, 1106, 2007年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Anti-influenza A virus activities of mannan-binding lectins and bovine conglutinin.
  Takao Kawai; Tetsuo Kase; Yasuhiko Suzuki; Souji Eda; Takashi Sakamoto; Katsuki Ohtani; Nobutaka Wakamiya
  The Journal of veterinary medical science, 69, 2, 221, 4, 2, 2007年02月, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Mannan-binding lectin (MBL) and bovine conglutinin (BKg) belong to the collectin family, which is involved in first-line host defense against various infectious agents. We have previously reported that human MBL inhibited type A influenza viral hemagglutination, infection and spreading to adjacent cells without complement activation. In this study, we investigated the direct antiviral activities of bovine MBL, rabbit MBL and BKg. All collectins used in this study inhibited viral infectivity and hemagglutination at concentrations of 0.02-0.3 microg/ml. They also demonstrated inhibitory activity against viral spreading. Like human MBL, bovine MBL and BKg showed antiviral activities at their physiological concentrations. These results suggest that mammalian MBLs and BKg may inhibit the spread of influenza A virus through the bloodstream.
• Enhancement of Legionella pneumophila culture isolation from microenvironments by macrophage infectivity potentiator (mip) gene-specific nested polymerase chain reaction
  Rungrat Nintasen; Fuangfa Utrarachkij; Kanokrat Siripanichgon; Adisak Bhumiratana; Yasuhiko Suzuki; Orasa Suthienkul
  MICROBIOLOGY AND IMMUNOLOGY, 51, 8, 777, 785, 2007年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Titanium and zirconium complexes with non-salicylaldimine-type imine-phenoxy chelate ligands: syntheses, structures, and ethylene-polymerization behavior.
  Yasuhiko Suzuki; Hidetsugu Tanaka; Toshiyuki Oshiki; Kazuhiko Takai; Terunori Fujita
  Chemistry, an Asian journal, 1, 6, 878, 87, 2006年12月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, New Ti and Zr complexes that bear imine-phenoxy chelate ligands, [{2,4-di-tBu-6-(RCH=N)-C6H4O}2MCl2] (1: M = Ti, R = Ph; 2: M = Ti, R = C6F5; 3: M = Zr, R = Ph; 4: M = Zr, R = C6F5), were synthesized and investigated as precatalysts for ethylene polymerization. 1H NMR spectroscopy suggests that these complexes exist as mixtures of structural isomers. X-ray crystallographic analysis of the adduct 1HCl reveals that it exists as a zwitterionic complex in which H and Cl are situated in close proximity to one of the imine nitrogen atoms and the central metal, respectively. The X-ray molecular structure also indicates that one imine phenoxy group with the syn C=N configuration functions as a bidentate ligand, whereas the other, of the anti C=N form, acts as a monodentate phenoxy ligand. Although Zr complexes 3 and 4 with methylaluminoxane (MAO) or [Ph3C]+ [B(C6F5)4]-/AliBu3 displayed moderate activity, the Ti congeners 1 and 2, in association with an appropriate activator, catalyzed ethylene polymerization with high efficiency. Upon activation with MAO at 25 degrees C, 2 displayed a very high activity of 19900 (kg PE) (mol Ti)(-1) h(-1), which is comparable to that for [Cp2TiCl2] and [Cp2ZrCl2], although increasing the polymerization temperature did result in a marked decrease in activity. Complex 2 contains a C6F5 group on the imine nitrogen atom and mediated nonliving-type polymerization, unlike the corresponding salicylaldimine-type complex. Conversely, with [Ph3C]+ [B(C6F5)4]-/AliBu3 activation, 1 exhibited enhanced activity as the temperature was increased (25-75 degrees C) and maintained very high activity for 60 min at 75 degrees C (18740 (kg PE) (mol Ti)(-1) h(-1)). 1H NMR spectroscopic studies of the reaction suggest that this thermally robust catalyst system generates an amine-phenoxy complex as the catalytically active species. The combinations 1/[Ph3C]+ [B(C6F5)4]-/AliBu3 and 2/MAO also worked as high-activity catalysts for the copolymerization of ethylene and propylene.
• Hafnocene catalysts for selective propylene oligomerization: efficient synthesis of 4-methyl-1-pentene by beta-methyl transfer.
  Yasuhiko Suzuki; Takahiro Yasumoto; Kazushi Mashima; Jun Okuda
  Journal of the American Chemical Society, 128, 39, 13017, 25, 2006年10月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, A series of hafnocene complexes (eta5-C5Me4R1)(eta5-C5Me4R2)HfCl2 with [R1, R2] = [H, H] (1), [Me, H] (2), [Me, Me] (3), [Et, Me] (4), [(i)Pr, Me] (5), [SiMe(3), Me] (6), [(t)Bu, Me] (7), [(n)Bu, Me] (8), [(i)Bu, Me] (9), [Et, Et] (10), [(n)Bu, (n)Bu] (11), [(i)Bu, (i)Bu] (12) was tested as catalyst precursors for propylene oligomerization. Upon activation with methylaluminoxane or [Ph(3)C][B(C(6)F(5))(4)]/Al(i)Bu(3), complexes 2-4 and 8-12 catalyzed the dimerization of propylene to produce 4-methyl-1-pentene with selectivities ranging from 23.9 to 61.6 wt % in the product mixture. The selectivity was dependent on the nature of the substituents R(1) and R(2), with the highest value found for (eta5-C5Me4(i)Bu)2HfCl2 (12). Rapid deactivation was observed for 5-7, whereas (eta5-C5Me4H)2HfCl2 (1) polymerized propylene. 4-Methyl-1-pentene is proposed to form by repeated 1,2-insertion of propylene into the hafnocene methyl cation, followed by selective beta-methyl elimination. Detailed analysis of the byproduct distribution (isobutene, 1-pentene, 2-methyl-1-pentene, 2,4-dimethyl-1-pentene, 4-methyl-1-heptene, 4,6-dimethyl-1-heptene), determined by gas chromatography, was performed with the aid of a stochastic simulation involving rate constants for the propagation by insertion, beta-hydride elimination, and beta-methyl elimination. The rate of termination is dependent on the structure of the growing chain of the active species as well as on the bulkiness of the cyclopentadienyl ligands. The selectivity highly depends on the reaction conditions (pressure, temperature, concentration of methylaluminoxane). The rates of beta-methyl elimination leading to 4-methyl-1-pentene were proportional to propylene pressure for 2-4 and 8-10 but practically independent from propylene pressure for the sterically bulkier derivatives 11-12.
• Expression and characterization of the genes encoding azoreductases from Bacillus subtilis and Geobacillus stearothermophilus
  Wataru Sugiura; Tomoko Yoda; Takashi Matsuba; Yoshinori Tanaka; Yasuhiko Suzuki
  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 70, 7, 1655, 1665, 2006年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvant
  T Ichinohe; Watanabe, I; E Tao; S Ito; A Kawaguchi; S Tamura; H Takahashi; H Sawa; M Moriyama; J Chiba; K Komase; Y Suzuki; T Kurata; T Sata; H Hasegawa
  JOURNAL OF MEDICAL VIROLOGY, 78, 7, 954, 963, 2006年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Human trachea primary epithelial cells express both sialyl(alpha 2-3)Gal receptor for human parainfluenza virus type 1 and avian influenza viruses, and sialyl(alpha 2-6)Gal receptor for human influenza viruses
  T Kogure; T Suzuki; T Takahashi; D Miyamoto; KIPJ Hidari; CT Guo; T Ito; Y Kawaoka; Y Suzuki
  GLYCOCONJUGATE JOURNAL, 23, 1-2, 101, 106, 2006年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Identification and characterization of a novel human collectin CL-K1
  Hiroyuki Keshi; Takashi Sakamoto; Takao Kawai; Katsuki Ohtani; Tsuyoshi Katoh; Seong-Jae Jang; Wataru Motomura; Takayuki Yoshizaki; Mitsuko Fukuda; Satoshi Koyama; Jun Fukuzawa; Atsushi Fukuoh; Itsuro Yoshida; Yasuhiko Suzuki; Nobutaka Wakamiya
  MICROBIOLOGY AND IMMUNOLOGY, 50, 12, 1001, 1013, 2006年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication
  T Suzuki; T Takahashi; CT Guo; KIPJ Hidari; D Miyamoto; H Goto; Y Kawaoka; Y Suzuki
  JOURNAL OF VIROLOGY, 79, 18, 11705, 11715, 2005年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 紫外線吸収剤及びその関連化合物によるエストロゲン様作用
  松本比佐志; 足立伸一; 鈴木定彦
  薬学雑誌, 125, 8, 643, 652, 2005年08月, ［国内誌］
  日本語, 研究論文（学術雑誌）
• Estrogenic activity of ultraviolet absorbers and the related compounds
  H Matsumoto; S Adachi; Y Suzuki
  YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 125, 8, 643, 652, 2005年08月, ［査読有り］
  日本語, 研究論文（学術雑誌）
• Bisphenol A in ambient air particulates responsible for the proliferation of MCF-7 human breast cancer cells and its concentration changes over 6 months
  H Matsumoto; S Adachi; Y Suzuki
  ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 48, 4, 459, 466, 2005年05月
  英語, 研究論文（学術雑誌）
• Characterization of multidrug-resistance phenotypes and genotypes of Escherichia coli strains isolated from swine from an abattoir in Osaka, Japan
  Y Kumai; Y Suzuki; Y Tanaka; K Shima; RK Bhadra; S Yamasaki; K Kuroda; G Endo
  EPIDEMIOLOGY AND INFECTION, 133, 1, 59, 70, 2005年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• 新しいアッセイ用哺乳類細胞(CHOOSER)を用いた簡便，高感度で再現性の良いエストロゲン様活性測定方法の開発
  足立伸一; 山本康次; 織田肇; 小野芳朗; 鈴木定彦
  水環境学会誌, 28, 7, 451, 456, 公益社団法人 日本水環境学会, 2005年
  日本語, Several in vitro assays have been developed to assess the activity of estrogenic substances. Recently, a yeast two-hybrid screen or a MCF-7 (human breast cancer cell) screen has been adopted mainly for screening chemicals and environmental estrogenic activity. However a yeast two-hybrid screen does not assay using an animal cell. MCF-7 screen is a complicated assay and the cell used proliferates depending on estrogen, thus obstructing a precise assay for estrogenic activity. In addition both screens need long incubation period (4-6 days) for a highly sensitive assay. The CHOOSER is a Chinese hamster ovary (CHO) cell transformed with the gene encoding the human estrogen receptor (ER α) and an estrogen responsive promoter linked to a reporter gene which was developed by Suzuki et. al. at Osaka prefectural institute of public health. When the reporter gene is activated by estrogenic substances, is expressed, producing alkaline phosphatase which is secreted into the medium. The CHOOSER can assay high sensitively (under 10-11M as 17 β-estradiol) at any time in a short incubation period (2 days). The number of the CHOOSER can be counted precisely because a CHO is dissociated the aggregates easily with trypsin and form a single cell suspension. And the CHOOSER can proliferate in the medium without estrogen, therefore it is possible to assay for estrogenic activity more proliferate in the medium without estrogen, therefore it is possible to assay for estrogenic activity more precisely. The CHOOSER assay will be a useful prescreening method for estrogenic activity before in vivo assay.
• Malignant mesothelioma of the tunica vaginalis testis: a case with a predominant sarcomatous component.
  Satoko Shimada; Kenzo Ono; Yasuhiko Suzuki; Naoyoshi Mori
  Pathology international, 54, 12, 930, 4, 2004年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, We present a case of malignant mesothelioma (MM) of the tunica vaginalis testis. A 64-year-old man was referred for an operation on a right hydrocele that later proved to be a tumor during surgery. The tumor was malignant with a biphasic pattern of epithelial and sarcomatous components. The latter component was predominant. Cuboidal or columnar cells formed irregular tubular structures in the epithelial component. In contrast, spindle-shaped or polygonal cells formed intricate structures with stromal connective tissues in the sarcomatous component. Immunohistochemical staining revealed that the tumor was mesothelial in origin and positive for cytokeratin, vimentin, HBME-1 antigen and calretinin. In general, MM occur in the pleura or peritoneum; those originating in the tunica vaginalis testis are very rare and represent less than 5% of all MM. In addition, MM in the tissues usually consist primarily of an epithelial component. According to previous reports tumors with a predominant sarcomatous component are extremely rare. In general, a sarcomatous component predicts poor prognosis and our case does, in fact, deteriorate over time. Our case suggests that despite its low incidence, MM must be considered when a case is diagnosed as hydrocele testicle.
• Identification of the Cryptosporidium isolate from chickens in Japan by sequence analyses
  A Kimura; Y Suzuki; T Matsui
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 66, 7, 879, 881, 2004年07月, ［国内誌］
  英語, 研究論文（学術雑誌）
• Choroidal neovascularization is provided by bone marrow cells.
  Minoru Tomita; Haruhiko Yamada; Yasushi Adachi; Yunze Cui; Eri Yamada; Akiko Higuchi; Keizo Minamino; Yasuhiko Suzuki; Miyo Matsumura; Susumu Ikehara
  Stem cells (Dayton, Ohio), 22, 1, 21, 6, 2004年, ［国際誌］
  英語, 研究論文（学術雑誌）, Choroidal neovascularization (CNV) is a known cause of age-related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.
• Characterization of clinical isolates of Mycobacterium tuberculosis resistant to drugs and detection of RpoB mutation in multidrug-resistant tuberculosis in the Philippines
  DMD Agdamag; S Kageyama; R Solante; AS Espantaleon; JCE Sangco; Y Suzuki
  INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, 7, 11, 1104, 1108, 2003年11月
  英語, 研究論文（学術雑誌）
• Cloning and expression of a UDP-glucuronic acid decarboxylase gene in rice
  K Suzuki; Y Suzuki; S Kitamura
  JOURNAL OF EXPERIMENTAL BOTANY, 54, 389, 1997, 1999, 2003年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Precise characterization of norovirus (Norwalk-like virus)-specific monoclonal antibodies with broad reactivity
  T Yoda; Y Suzuki; Y Terano; K Yamazaki; N Sakon; T Kuzuguchi; H Oda; T Tsukamoto
  JOURNAL OF CLINICAL MICROBIOLOGY, 41, 6, 2367, 2371, 2003年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• DNAマイクロアレイを用いた臨床分離結核菌の薬剤耐性判定
  吉川陽子; 市原竜生; 鈴木定
  臨床微生物迅速診断研究会誌, 14, 45, 50, 2003年
• Haplotype analysis of the human collectin placenta 1 (hCL-P1) gene
  H Ohmori; Y Makita; M Funamizu; S Chiba; K Ohtani; Y Suzuki; N Wakamiya; A Hata
  JOURNAL OF HUMAN GENETICS, 48, 2, 82, 85, 2003年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• [Detection of drug-resistant Mycobacterium tuberculosis isolates using DNA microarray].
  Yoko Yoshikawa; Tatsuo Ichihara; Yasuhiko Suzuki
  Rinsho Biseibutsu Jinsoku Shindan Kenkyukai shi = JARMAM : Journal of the Association for Rapid Method and Automation in Microbiology, 14, 1, 45, 50, 2003年, ［国内誌］
  日本語, 研究論文（学術雑誌）, Rapid identification of drug-resistant strains of Mycobacterium tuberculosis is an important problem to adequate patient treatment. However, current clinical assays for determining antibiotic susceptibility in M. tuberculosis require many weeks to complete due to the slow growth of the bacilli. We have developed simple and rapid drug susceptibility test using DNA microarray "Oligoarray TB," that allows the detection of rifampicin (RFP), isoniazide (INH), kanamycin (KM), streptomycin (SM), and ethambutol (EM)-resistant strains within 6 h with DNA extracted directly from sputum or cultured cells. The genes related to drug-resistance, results of detection using Oligoarray TB, comparative evaluation with media, and sequencing analysis of strains generating discrepant results in testing for INH-resistant will be discussed in this presentation.
• Molecular cloning of mouse collectin liver 1
  T Kawai; Y Suzuki; S Eda; T Kase; K Ohtani; Y Sakai; H Keshi; A Fukuoh; T Sakamoto; M Nozaki; NG Copeland; NA Jenkins; N Wakamiya
  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 66, 10, 2134, 2145, 2002年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Isolation of a novel mouse variant of the drs tumor suppressor gene
  T Kawai; Y Suzuki; A Yamashita; H Inoue
  CANCER LETTERS, 183, 1, 79, 86, 2002年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Molecular cloning and characterization of chick sialoprotein associated with cones and rods, a developmentally regulated glycoprotein of interphotoreceptor matrix.
  Masahiro Zako; Masayoshi Iwaki; Masahiko Yoneda; Osamu Miyaishi; Jinsong Zhao; Yasuhiko Suzuki; Makoto Takeuchi; Goichiro Miyake; Hiroshi Ikagawa; Koji Kimata
  The Journal of biological chemistry, 277, 28, 25592, 600, 2002年07月12日, ［国際誌］
  英語, 研究論文（学術雑誌）, MY-174 is an IgM class monoclonal antibody originally established against chick PG-M/versican. The antibody specifically stains the photoreceptor layer, where we recently reported an absence of PG-M/versican. In this study, we re-characterized the antibody and identified the molecule that reacts to MY-174 at the photoreceptor layer. Immunohistochemistry localized the antigen to the matrix surrounding photoreceptors. A variety of glycosidase digestions showed that the antigen is the 150-kDa glycoprotein that has sialylated N- and O-linked glycoconjugates having a molecular mass of more than 30-kDa. The peptide sequences obtained from purified MY-174 antigen showed we had sequenced a full-length cDNA with an open reading frame of 2787 base pairs, encoding a polypeptide of 928 amino acids, with 56 and 54% identities to human and mouse sialoprotein associated with cones and rods (SPACRs), respectively, and with the structural features observed in SPACRs. The specific sialylated O-glycoconjugates here are involved in the epitope structure for MY-174. SPACR first appeared by embryonic days 15-16, and expression increased with developmental age, paralleling the adhesion between neural retina and retinal pigment epithelium. Thus, we concluded that the MY-174 antigen at the photoreceptor layer, a developmentally regulated glycoprotein, is identical to chick SPACR and may be involved in a novel system mediating adhesion between neural retina and retinal pigment epithelium.
• Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice
  T Shimada; K Inoue; Y Suzuki; T Kawai; E Azuma; T Nakajima; M Shindo; K Kurose; A Sugie; Y Yamagishi; Y Fujii-Kuriyama; M Hashimoto
  CARCINOGENESIS, 23, 7, 1199, 1207, 2002年07月
  英語, 研究論文（学術雑誌）
• Rapid detection of pyrazinamide-resistant Mycobacterium tuberculosis by a PCR-based in vitro system
  Y Suzuki; A Suzuki; A Tamaru; C Katsukawa; H Oda
  JOURNAL OF CLINICAL MICROBIOLOGY, 40, 2, 501, 507, 2002年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection
  Y Hakozaki; M Yoshiba; K Sekiyama; E Seike; J Iwamoto; K Mitani; M Mine; T Morizane; K Ohtani; Y Suzuki; N Wakamiya
  LIVER, 22, 1, 29, 34, 2002年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Identification of human mannose binding lectin (MBL) recognition sites for novel inhibitory antibodies.
  Hui Zhao; Nobutaka Wakamiya; Yasuhiko Suzuki; Matthew T Hamonko; Gregory L Stahl
  Hybridoma and hybridomics, 21, 1, 25, 36, 1, 2002年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Mannose binding lectin (MBL) binding initiates activation of the lectin complement pathway. Recent studies from our laboratory have demonstrated that MBL-dependent complement activation mediates cellular injury following oxidative stress in vivo and in vitro. A panel of novel inhibitory monoclonal antibodies (MAbs) against MBL (e.g., MAb 3F8, 2A9, and hMBL1.2) has been developed that inhibit MBL binding and lectin pathway activation. Here, we further characterized the interactions of these MAbs and their Fab fragments to MBL. Whole MAbs or their Fab fragments bound to MBL with relatively high affinity. Fab fragments of 3F8 were functionally effective in inhibiting MBL-dependent complement activation, however, steric hindrance of MAb 2A9 was essential for inhibition of MBL-dependent complement activation. We identified the hinge region, and residues EDCVLLL within the carbohydrate recognition domain of MBL as the recognition sites for MAb 3F8 and 2A9, respectively. The interaction of MAbs (e.g., 3F8 and 2A9) to MBL was dependent on the conformation of their recognition sites. These findings demonstrate that MBL binding can be inhibited by at least two separate and independent mechanisms.
• The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Keshi; Y Sakai; A Fukuoh; T Sakamoto; H Itabe; T Suzutani; M Gasawara; Yoshida, I; N Wakamiya
  JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 47, 44222, 44228, 2001年11月
  英語, 研究論文（学術雑誌）
• Characterization of Norwalk virus GI specific monoclonal antibodies generated against Escherichia coli expressed capsid protein and the reactivity of two broadly reactive monoclonal antibodies generated against GII capsid towards GI recombinant fragments
  Tomoko Yoda; Yoshitake Terano; Yasuhiko Suzuki; Kenji Yamazaki; Isao Oishi; Tsuyoshi Kuzuguchi; Hiroyoshi Kawamoto; Etsuko Utagawa; Koichi Takino; Hajime Oda; Tadayoshi Shibata
  BMC Microbiology, 1, 1, 1, 11, BioMed Central Ltd., 2001年10月08日
  英語, 研究論文（学術雑誌）
• Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall
  S Tsuji; J Uehori; M Matsumoto; Y Suzuki; A Matsuhisa; K Toyoshima; T Seya
  JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 26, 23456, 23463, 2001年06月
  英語, 研究論文（学術雑誌）
• Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome
  A Tsutsumi; K Sasaki; N Wakamiya; K Ichikawa; T Atsumi; K Ohtani; Y Suzuki; T Koike; T Sumida
  Genes Immun., 2, 2, 99, 104, 2001年04月
  英語, 研究論文（学術雑誌）
• Recombinant expression of human mannan-binding lectin
  T Vorup-Jensen; ES Sorensen; UB Jensen; W Schwaeble; T Kawasaki; Y Ma; K Uemura; N Wakamiya; Y Suzuki; TG Jensen; K Takahashi; RAB Ezekowitz; S Thiel; JC Jensenius
  INTERNATIONAL IMMUNOPHARMACOLOGY, 1, 4, 677, 687, 2001年04月
  英語, 研究論文（学術雑誌）
• Molecular cloning and characterization of the gene coding for azoreductase from Bacillus sp OY1-2 isolated from soil
  Y Suzuki; T Yoda; A Ruhul; W Sugiura
  JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 12, 9059, 9065, 2001年03月
  英語, 研究論文（学術雑誌）
• Molecular cloning of CL-P1 gene
  N Wakamiya; Y Suzuki
  SEIKAGAKU, 73, 3, 205, 208, 2001年03月, ［査読有り］
  日本語, 研究論文（学術雑誌）
• Usefulness of self ligation mediated polymerase chain reaction: a rapid method for fingerprinting in molecular epidemiology of tuberculosis.
  アミン ルフル; 鈴木 定彦; 高鳥毛 敏雄; 多田羅 浩三; 白倉 良太
  Kekkaku, 76, 1, 9, 18, JAPANESE SOCIETY FOR TUBERCULOSIS, 2001年
  英語, 結核菌の中に挿入されているDNA断片IS6110をプローブとしたRFLP分析が結核の疫学や診断の強力な手段の1つとして利用されている。しかし, RFLP分析を行うにはDNA量が1 micro-gram以上必要であり, 検査結果が出るまでに2日を要する難点がある。そこで, われわれはこの不便さを克服するためにPCRの技術を利用した新たな検査方法であるSelf Ligation Mediated Polymerase Chain Reaction (SL-PCR) 法を開発した。この方法は, IS6110の内側から外側向きに配列した1対のプライマーを用いるものである。DNA断片のIS6110を制限酵素Sau 3A Iを使って分解し, PCR法を使って増幅させ, 結核菌の染色体のDNAと結合させる方法である。この方法を用いることにより, 結核菌の株を8時間以内で識別することが可能となる。今後, 結核患者の接触者調査や結核蔓延状況の解明などのスクリーニング検査法としても活用しうる方法である。
• 日本人におけるMBL(mannan-binding lectin)遺伝子変異と血中濃度の検討
  芥子 宏行; 大谷 克城; 坂本 隆志; 岸 雄一郎; 荒木 宏昌; 鈴木 定彦; 若宮 伸隆
  医学のあゆみ, 194, 12, 957, 958, 医歯薬出版(株), 2000年09月, ［査読有り］
  日本語, 研究論文（学術雑誌）, 健常日本人497例におけるMBL遺伝子変異と血中濃度の測定により,MBLの遺伝子多型はコドン54のみにみられ,その頻度は野生型70.8%,ヘテロ変異型22.5%,ホモ変異型6.7%であった.本ホモ変異型の比率は欧米の比率に比べて高値であるが,血中濃度とgenotypeが十分相関しており,今後,MBLの関与が考えられる各種疾患群との比較において日本人のMBL遺伝子多型と血中濃度の一つのスタンダードになりうる
• Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection
  K Sasaki; A Tsutsumi; N Wakamiya; K Ohtani; Y Suzuki; Y Watanabe; N Nakayama; T Koike
  SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 35, 9, 960, 965, 2000年09月
  英語, 研究論文（学術雑誌）
• Expression of recombinant Norwalk-like virus capsid proteins using a bacterial system and the development of its immunologic detection
  T Yoda; Y Terano; A Shimada; Y Suzuki; K Yamazaki; N Sakon; Oishi, I; ET Utagawa; Y Okuno; T Shibata
  JOURNAL OF MEDICAL VIROLOGY, 60, 4, 475, 481, 2000年04月
  英語, 研究論文（学術雑誌）
• A comparative analysis of the antigenic, structural, and functional properties of three different preparations of recombinant human interleukin-18
  S Kikkawa; K Shida; H Okamura; NA Begum; M Matsumoto; S Tsuji; M Nomura; Y Suzuki; K Toyoshima; T Seya
  JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 20, 2, 179, 185, 2000年02月
  英語, 研究論文（学術雑誌）
• Characterization of monoclonal antibodies generated against Norwalk virus GII capsid protein expressed in Escherichia coli
  T Yoda; Y Terano; Y Suzuki; K Yamazaki; Oishi, I; E Utagawa; A Shimada; S Matsuura; M Nakajima; T Shibata
  MICROBIOLOGY AND IMMUNOLOGY, 44, 11, 905, 914, 2000年
  英語, 研究論文（学術雑誌）
• The 3’-UT of the ubiquitous mRNA of human CD46 confers selective suppression of protein production in murine cells
  SHIDA K; NOMURA M; MATSUMOTO M; SUZUKI Y; TOYOSHIMA K; SEYA T
  Eur J Immunol, 29, 11, 3603, 3608, 1999年11月
  英語, 研究論文（学術雑誌）
• RFLP分析による結核小規模感染事例の疫学的研究
  田丸亜貴; 鈴木定彦
  結核, 74, 7, 555, 561, 1999年07月, ［査読有り］
  日本語, 研究論文（学術雑誌）
• Human mannan-binding lectin inhibits the infection of influenza A virus without complement
  T Kase; Y Suzuki; T Kawai; T Sakamoto; K Ohtani; S Eda; A Maeda; Y Okuno; T Kurimura; N Wakamiya
  IMMUNOLOGY, 97, 3, 385, 392, 1999年07月
  英語, 研究論文（学術雑誌）
• Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines
  M Kurita; M Matsumoto; S Tsuji; M Kawakami; Y Suzuki; H Hayashi; K Toyoshima; T Seya
  CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 116, 3, 547, 553, 1999年06月
  英語, 研究論文（学術雑誌）
• Molecular cloning of a novel human collectin from liver (CL-L1)
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Yamazaki; T Shimada; H Keshi; Y Sakai; A Fukuoh; T Sakamoto; N Wakamiya
  JOURNAL OF BIOLOGICAL CHEMISTRY, 274, 19, 13681, 13689, 1999年05月
  英語, 研究論文（学術雑誌）
• 大阪府下で採取された結核臨床分離株のRFLP分析
  田丸 亜貴; 勝川 千尋; 鈴木 定彦
  結核, 74, 3, 322, 322, (一社)日本結核・非結核性抗酸菌症学会, 1999年03月
  日本語
• 臨床分離株を用いた結核菌感受性PZA液体培地法の検討
  中曽根 智恵; 石田 智恵子; 高嶋 哲也; 田丸 亜貴; 鈴木 定彦; 勝川 千尋
  結核, 74, 3, 327, 327, (一社)日本結核・非結核性抗酸菌症学会, 1999年03月
  日本語
• 血清マンナン結合蛋白質のハンセン病における役割に関する研究
  鈴木 定彦; 勝川 千尋; 田丸 亜貴; Ruhul Amin; 牧野 正直; 若宮 伸隆
  日本ハンセン病学会雑誌, 68, 1, 50, 50, 日本ハンセン病学会, 1999年03月, ［査読有り］
  日本語
• Preparation of recombinant alpha2 antigen of M. leprae in E. coli and the application for sero-diagnosis of leprosy.
  Yin Y; Suzuki Y; Makino M; Wu Q; Hou W
  Chin. Med. Sci. J., 14, 106, 1999年, ［査読有り］
  中国語, 研究論文（学術雑誌）
• Gene cloning and expression of Mycobacterium leprae alpha 2 antigen.
  Yin Y; Suzuki Y; Makino M; Wu Q
  Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 21, 62, 68, 1999年, ［査読有り］
  中国語, 研究論文（学術雑誌）
• High-level and effective production of human mannan-binding lectin (MBL) in Chinese hamster ovary (CHO) cells
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Keshi; Y Sakai; S Yamamoto; T Sakamoto; N Wakamiya
  JOURNAL OF IMMUNOLOGICAL METHODS, 222, 1-2, 135, 144, 1999年01月
  英語, 研究論文（学術雑誌）
• Characterization of truncated human mannan-binding protein (MBP) expressed in Escherichia coli
  S Eda; Y Suzuki; T Kawai; K Ohtani; T Kase; T Sakamoto; N Wakamiya
  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 62, 7, 1326, 1331, 1998年07月
  英語, 研究論文（学術雑誌）
• Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of Warfarin, flurbiprofen, and diclofenac by human liver microsomes
  H Yamazaki; K Inoue; K Chiba; N Ozawa; T Kawai; Y Suzuki; JA Goldstein; FP Guengerich; T Shimada
  BIOCHEMICAL PHARMACOLOGY, 56, 2, 243, 251, 1998年07月
  英語, 研究論文（学術雑誌）
• Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene
  Y Suzuki; C Katsukawa; A Tamaru; C Abe; M Makino; Y Mizuguchi; H Taniguchi
  JOURNAL OF CLINICAL MICROBIOLOGY, 36, 5, 1220, 1225, 1998年05月
  英語, 研究論文（学術雑誌）
• Post-translational modification and intracellular localization of a splice product of CD46 cloned from human testis: role of the intracellular domains in O-glycosylation
  T Hara; Y Suzuki; T Nakazawa; H Nishimura; S Nagasawa; M Nishiguchi; M Matsumoto; M Hatanaka; M Kitamura; T Seya
  IMMUNOLOGY, 93, 4, 546, 555, 1998年04月
  英語, 研究論文（学術雑誌）
• Molecular and biological characterization of rabbit mannan-binding protein (MBP)
  T Kawai; Y Suzuki; S Eda; K Ohtani; T Kase; T Sakamoto; H Uemura; N Wakamiya
  GLYCOBIOLOGY, 8, 3, 237, 244, 1998年03月
  英語, 研究論文（学術雑誌）
• Regulation of promoter and intron enhancer activity in immunoglobulin heavy chain genes through late stage of B cell development
  Microbiol . Immunol, 42, 399, 405, 1998年
• Characterization of the rpsL and rrs genes of streptomycin-resistant clinical isolates of Mycobacterium tuberculosis in Japan
  E Katsukawa; A Tamaru; Y Miyata; C Abe; M Makino; Y Suzuki
  JOURNAL OF APPLIED MICROBIOLOGY, 83, 5, 634, 640, 1997年11月
  英語, 研究論文（学術雑誌）
• Characterization of recombinant bovine conglutinin expressed in a mammalian cell
  Y Suzuki; S Eda; T Kawai; K Ohtani; T Kase; T Sakamoto; N Wakamiya
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 238, 3, 856, 860, 1997年09月
  英語, 研究論文（学術雑誌）
• Complete nucleotide sequence of the chloroplast genome from the green alga Chlorella vulgaris: The existence of genes possibly involved in chloroplast division
  T Wakasugi; T Nagai; M Kapoor; M Sugita; M Ito; S Ito; J Tsudzuki; K Nakashima; T Tsudzuki; Y Suzuki; A Hamada; T Ohta; A Inamura; K Yoshinaga; M Sugiura
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94, 11, 5967, 5972, 1997年05月
  英語, 研究論文（学術雑誌）
• Molecular cloning and sequence analysis of the cDNA for the mouse counterpart to adult hamster liver purified growth inhibitory factor
  C Hashimoto; H Masuda; M Ayaki; Y Suzuki; A Uenaka; T Seya; J Miyoshi; K Takahashi; Y Inui
  BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1355, 3, 205, 208, 1997年03月
  英語, 研究論文（学術雑誌）
• Swine influenza virus strains recognize sialylsugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epithelium
  T Suzuki; G Horiike; Y Yamazaki; K Kawabe; H Masuda; D Miyamoto; M Matsuda; SI Nishimura; T Yamagata; T Ito; H Kida; Y Kawaoka; Y Suzuki
  FEBS LETTERS, 404, 2-3, 192, 196, 1997年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Cloning and characterization of a cDNA encoding bovine mannan-binding protein
  T Kawai; Y Suzuki; S Eda; K Ohtani; T Kase; Y Fujinaga; T Sakamoto; T Kurimura; N Wakamiya
  GENE, 186, 2, 161, 165, 1997年02月
  英語, 研究論文（学術雑誌）
• Recombinant human surfactant protein D, lacking the N-terminal and collagenouse domains, has less bacterial agglutinating activity but is able to inhibit haemagglutination by influenze A virus
  Biochem. J., 323, 393, 399, 1997年
• Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species
  T Ito; Y Suzuki; L Mitnaul; A Vines; H Kida; Y Kawaoka
  VIROLOGY, 227, 2, 493, 499, 1997年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Recombinant bovine conglutinin, lacking the N-terminal and collagenous domains, has less conglutination activity but is able to inhibit haemagglutination by influenza A virus
  S Eda; Y Suzuki; T Kase; T Kawai; K Ohtani; T Sakamoto; T Kurimura; N Wakamiya
  BIOCHEMICAL JOURNAL, 316, 316, 43, 48, 1996年05月
  英語, 研究論文（学術雑誌）
• Variation in sialyl sugar chain mediated recognition by the hemagglutinin and sialidase of human influenza viruses
  Y Suzuki; T Ito; Y Maejima; H Masuda; G Horiike; T Suzuki; K Sato; G Hanagata; M Kiso; A Hasegawa; GY Xu; T Ito; Y Kawaoka; RG Webster
  OPTIONS FOR THE CONTROL OF INFLUENZA III, 1123, 443, 446, 1996年, ［査読有り］, ［国際共著］, ［国際誌］
  英語, 研究論文（国際会議プロシーディングス）
• High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation
  T Hara; Y Suzuki; T Semba; M Hatanaka; M Matsumoto; T Seya
  SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 42, 6, 581, 590, 1995年12月
  英語, 研究論文（学術雑誌）
• わが国のリファンピシン耐性臨床分離結核菌におけるrpoB遺伝子の変異
  鈴木 定彦; 勝川 千尋; 井上 清
  感染症学雑誌, 69, 4, 413, 419, (一社)日本感染症学会, 1995年04月
  英語, 小川培地上に生育した結核菌標準株4株(H37Ra株,H37Rv株,青山B株,ATCC35416株),リファンピシン耐性臨床分離結核菌株47株および感受性臨床分離結核菌株17株より抽出したDNAを鋳型としてPCRを行い411塩基対のrpoB遺伝子断片を増幅させた。ストレプトアビジン化ダイナビーズを用いた直接塩基配列決定法によりこのDNA断片の塩基配列を決定し,相互に比較した結果,この遺伝子領域の変異とリファンピシン耐性の間に非常に高い相関が見られた。リファンピシン耐性株47株中44株において変異が検出された。これに対して,感受性株17株および標準株4株においては,まったく変異が検出されなかった
• Mutations in rpoB gene of rifampicin resistant clinical isolates of Mycobacterium tuberculosis in Japan
  J. Jpn. Assoc. Infect. Dis., 69, 413, 41, 1995年
• FLUORESCENCE IN-SITU HYBRIDIZATION ANALYSIS OF CHROMOSOMAL LOCALIZATION OF 3 HUMAN CYTOCHROME-P450-2C GENES (CYP2C8, 2C9, AND 2C10) AT 10Q24.1
  K INOUE; J INAZAWA; Y SUZUKI; T SHIMADA; H YAMAZAKI; FP GUENGERICH; T ABE
  JAPANESE JOURNAL OF HUMAN GENETICS, 39, 3, 337, 343, 1994年09月
  英語, 研究論文（学術雑誌）
• Comparizon of somatic mutation frequency among immunoglobulin genes
  MOTOYAMA N; MIWA T; SUZUKI Y; OKADA H; AZUMA T
  J. Exp. Med., 179, 2, 395, 403, 1994年
• CLONING AND SEQUENCING OF A CDNA CODING FOR BOVINE CONGLUTININ
  Y SUZUKI; YP YIN; M MAKINO; T KURIMURA; N WAKAMIYA
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 191, 2, 335, 342, 1993年03月
  英語, 研究論文（学術雑誌）
• INDUCIBILITY OF PROTEIN-REACTIVE ANTIBODIES BY PEPTIDE IMMUNIZATION - COMPARISON OF 3 EPITOPE PEPTIDES OF HEN EGG-WHITE LYSOZYME
  J SEKI; XH WANG; A OTA; Y SUZUKI; N SAKATO; H FUJIO
  JOURNAL OF BIOCHEMISTRY, 111, 2, 259, 264, 1992年02月
  英語, 研究論文（学術雑誌）
• ANALYSIS OF THE PROMOTER REGION IN THE RIBOSOMAL-RNA OPERON FROM MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; A NAGATA; T YAMADA
  ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY, 60, 1, 7, 11, 1991年07月
  英語, 研究論文（学術雑誌）
• HUMAN BRAIN PROSTAGLANDIN-D SYNTHASE HAS BEEN EVOLUTIONARILY DIFFERENTIATED FROM LIPOPHILIC-LIGAND CARRIER PROTEINS
  A NAGATA; Y SUZUKI; M IGARASHI; N EGUCHI; H TOH; Y URADE; O HAYAISHI
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 88, 9, 4020, 4024, 1991年05月
  英語, 研究論文（学術雑誌）
• Studies on antinephritic effects of plant components in rats (2): Effects of ginsenosides on original-type anti-GBM nephritis in rats and its mechanisms
  T. Hattori; M. Ito; Y. Suzuki
  Folia Pharmacologica Japonica, 97, 2, 127, 134, 1991年
  日本語, 研究論文（学術雑誌）
• ACTIVATION OF IDIOTYPE-SPECIFIC CD4+ T-CELL LINE - CELLULAR PROCESSING OF EXOGENOUS SELF-IMMUNOGLOBULIN
  N SAKATO; P RUGDECH; T YODA; A OTA; Y ZHAO; M SEMMA; Y SUZUKI; H FUJIO
  IMMUNOLOGY, 71, 2, 153, 157, 1990年10月
  英語, 研究論文（学術雑誌）
• Primary Structure of Rat Mrain Prostaglandin D Synthetase Deduced from cDNA Sequence
  J. Biol Che., 264, 1041, 1045, 1989年
• Primary Structure of Rat Brain Prostaglandin D Synthetase Deduced from the cDNA Sequence
  YOSHIHIRO URADE; AKIHISA NAGATA; YASUHIKO SUZUKI; YUTAKA FUJII; OSAMU HAYAISHI
  Annals of the New York Academy of Sciences, 559, 1, 491, 493, 1989年, ［査読有り］
  英語, 研究論文（学術雑誌）
• COMPLETE NUCLEOTIDE-SEQUENCE OF THE 16S RIBOSOMAL-RNA GENE OF MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; A NAGATA; Y ONO; T YAMADA
  JOURNAL OF BACTERIOLOGY, 170, 6, 2886, 2889, 1988年06月
  英語
• MOLECULAR-CLONING AND CHARACTERIZATION OF AN RIBOSOMAL-RNA OPERON IN STREPTOMYCES-LIVIDANS TK21
  Y SUZUKI; Y ONO; A NAGATA; T YAMADA
  JOURNAL OF BACTERIOLOGY, 170, 4, 1631, 1636, 1988年04月
  英語, 研究論文（学術雑誌）
• The nucieotide sequence of 16S rRNA gene from Streptomyces lividans Tk21
  Yasuhiko Suzuki; Takeshi Yamada
  Nucleic Acids Research, 16, 1, 370, 1988年01月11日
  英語, 研究論文（学術雑誌）
• Mycobacterium phlei のリボソームRNA遺伝子の解析
  鈴木定彦; 山田毅
  結核, 63, 1, 1, 3, 1988年, ［査読有り］
  英語, 研究論文（学術雑誌）
• STUDY ON RIBOSOMAL-RNA GENES IN MYCOBACTERIUM-SMEGMATIS
  Y SUZUKI; T YAMADA
  MICROBIOLOGY AND IMMUNOLOGY, 32, 12, 1259, 1262, 1988年
  英語
• Chlorella chloroplast DNA seguence containing a gene for the large subunit of ribulose-1, 5-bisphosphate carboxylase/oxygenase and a part of a possible gene for the beta’s subunit of RNA polymerase
  K YOSHINAGA; T OHTA; Y SUZUKI; M SUGIURA
  Plant Mol. Biol, 10, 3, 245, 250, 1988年
  英語, 研究論文（学術雑誌）
• THE NUMBER OF RIBOSOMAL-RNA GENES IN MYCOBACTERIUM-LEPRAEMURIUM
  Y SUZUKI; T MORI; Y MIYATA; T YAMADA
  FEMS MICROBIOLOGY LETTERS, 44, 1, 73, 76, 1987年09月
  英語, 研究論文（学術雑誌）
• ORGANIZATION OF RIBOSOMAL-RNA GENES IN MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; K YOSHINAGA; Y ONO; A NAGATA; T YAMADA
  JOURNAL OF BACTERIOLOGY, 169, 2, 839, 843, 1987年02月
  英語, 研究論文（学術雑誌）
• ALTERATION OF RIBOSOMES AND RNA-POLYMERASE IN DRUG-RESISTANT CLINICAL ISOLATES OF MYCOBACTERIUM-TUBERCULOSIS
  T YAMADA; A NAGATA; Y ONO; Y SUZUKI; T YAMANOUCHI
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 27, 6, 921, 924, 1985年
  英語, 研究論文（学術雑誌）
• RAPID PREPARATION OF PLASMID BY GEL-PERMEATION CHROMATOGRAPHY ON TOYOPEARL HW75S
  K YOSHINAGA; Y SUZUKI
  AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 47, 4, 919, 920, 1983年
  英語

• らい菌のDNAジャイレースに着目した温度と活性の解析
  八代龍; 金玄; PONDPAN Suwanthada; POUSSIER Charlotte; 中島千絵; 鈴木定彦; 阿戸学; 中田登, Japanese Journal of Leprosy, 95, 1, 2026年
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  河喜多智美; 河喜多智美; 輿石雄一; 大野円実; 大野円実; 関屋俊輝; 関屋俊輝; 野村直樹; HANDABILE Chimuka; HANDABILE Chimuka; OBENG-KYEREMEH Richard; ZHANG Saicheng; 中島千絵; 中島千絵; 鈴木定彦; 鈴木定彦; 新開大史; 新開大史; 伊藤壽啓; 伊藤壽啓; 喜田宏; 喜田宏, 日本生体防御学会学術総会講演抄録集, 36th, 2025年
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  野間井智; 福原秀雄; 福原秀雄; 福原秀雄; 福原秀雄; 喜多俊介; DOKAINISH Hisham M.; 田畑耕史郎; 田畑耕史郎; 高巣晃; 高巣晃; HUISKONEN Juha T.; 安楽佑樹; 染谷太陽; 大野円実; 大野円実; 大野円実; 新開大史; 新開大史; 喜田宏; 喜田宏; 千田俊哉; 千田俊哉; 千田俊哉; STUART David I.; 佐々木道仁; 大場靖子; 鈴木定彦; 鈴木定彦; 澤洋文; 澤洋文; 澤洋文; 澤洋文; 前仲勝実; 前仲勝実; 前仲勝実; 前仲勝実; 前仲勝実, 日本生化学会大会(Web), 98th, 2025年
• 抗PD-L1ウマキメラ抗体の樹立およびウマの悪性腫瘍に対する抗腫瘍効果の検証
  堀川壮琉; 岡川朋弘; 岡川朋弘; GANBAATAR Otgontuya; TIYAMANEE Wisa; 前川直也; 北内諒; 山家祟史; 鈴木定彦; 鈴木定彦; 賀川由美子; 村田史郎; 大橋和彦; 加藤幸成; 加藤史樹; 今内覚; 今内覚, 日本獣医学会学術集会講演要旨集, 168th, 2025年
• イヌ常在菌Staphylococcus pseudintermedius由来SpsQとイヌIgGとの結合性の評価
  竹内寛人; 竹内寛人; 中島千絵; 今内覚; 今内覚; 今内覚; 前川直也; 岡川朋弘; 岡川朋弘; 臼井優; 田村豊; 鈴木定彦; 村田史郎; 大橋和彦; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 168th, 2025年
• アルカリ処理によるポリマーピエゾバイオセンサ素子の表面改質
  村田佳菜子; 小林祐騎; 荻谷泰斗; 武田真理子; 秀島翔; 宗像文男; 中島千絵; 鈴木定彦, センサ・マイクロマシンと応用システムシンポジウム(CD-ROM), 41st, 2024年
• BSL3クライオ電子顕微鏡を用いたSARS-CoV-2の構造解析
  福原秀雄; DOKAINISH Hisham; 喜多俊介; 田畑耕史郎; 田畑耕史郎; 高巣晃; HUISKONEN Juha; 安楽佑樹; 千田俊哉; 千田俊哉; 千田俊哉; STUART David; 佐々木道仁; 大場靖子; 鈴木定彦; 鈴木定彦; 澤洋文; 澤洋文; 前仲勝実; 前仲勝実; 前仲勝実, 日本生体防御学会学術総会講演抄録集, 35th (Web), 2024年
• 抗PD-L1抗体により治療した悪性黒色腫の犬における血清バイオマーカーの探索
  飯高早紀子; 前川直也; 今内覚; 出口辰弥; 岡川朋弘; 高木哲; 高木哲; 鈴木定彦; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 167th, 2024年
• 世界の結核研究の動向(40)結核菌の薬剤耐性と遺伝子変異について
  中島千絵; 鈴木定彦, 複十字, 415, 2024年
• 比較ゲノム解析による乳牛由来黄色ブドウ球菌の国際的な拡散状況の解明
  大川佳穂; 福田昭; 米山裕; 戸部隆太; 中島千絵; 中島千絵; 鈴木定彦; 鈴木定彦; 臼井優, 北海道獣医師会雑誌, 68, 8, 2024年
• 伴侶動物由来メチシリン耐性Staphylococcus pseudintermediusの現状と人獣共通感染症の可能性
  盛田佐和; 福田昭; 岡村幸一; 小松忠人; 露木勇三; 鳥居花衣; 佐々木潤平; 鈴木定彦; 中島千絵; 臼井優, 動物用抗菌剤研究会報, 45, 2023年
• 鼻疽菌検出のための新規dry LAMP法の開発
  中瀬満; THAPA Jeewan; BATBAATAR Vanaabaatar; KHURTSBAATAR Ochirbat; ENKHTUUL Batchuluun; UNENBAT Jugderkhorloo; 中島千絵; 鈴木定彦; 木村享史, 日本獣医学会学術集会講演要旨集, 166th, 2023年
• 免疫チェックポイント分子Programmed death-ligand1(PD-L1)を標的とした抗体薬による犬の鼻腔内腺癌に対する免疫療法の検討
  多田佳史; 前川直也; 今内覚; 細谷謙次; 大脇稜; 竹内寛人; 賀川由美子; 高木哲; 高木哲; 鈴木定彦; 鈴木定彦; 岡川朋弘; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 166th, 2023年
• 低温調理における耐熱性細菌・非耐熱性細菌の死滅条件の解明
  中野瞳; 福田昭; 中島千絵; 鈴木定彦; 臼井優, 北海道獣医師会雑誌, 66, 8, 2022年
• ブタPD-1/PD-L1経路の発現と機能解析【JST・京大機械翻訳】
  OTGONTUYA Ganbaatar; 今内覚; 岡川朋弘; 野島裕太郎; 前川直也; 市川世識; 小林篤史; 芝原友幸; 柳川洋二郎; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年
• 動物用抗体医薬品の開発および臨床研究
  今内 覚; 岡川 朋弘; 前川 直也; 中島 千絵; 鈴木 定彦; 山本 啓一; 戸田 幹洋; 村田 史郎; 大橋 和彦, JVPA digest : 日本動物用医薬品協会会報, 67, 1, 10, 2020年02月
  日本動物薬事協会, 日本語
• 等温増幅とDNAクロマトグラフィーによるリファンピシン耐性結核菌の多重変異検出方の開発
  宝田裕; 小寺拓也; 小林久美; 中島千絵; 中島千絵; 川瀬三雄; 鈴木定彦; 鈴木定彦, 日本分子生物学会年会プログラム・要旨集(Web), 43rd, 2020年
• Molecular characterization and antimicrobial resistance of MRSA from pigs and pork in Thailand(和訳中)
  Tanomsridachchai Wimonrat; 中島 千絵; Changkaew Kanjana; Changkwanyeun Ruchirada; Prapasawat Watsawan; Intarapuk Apiradee; Yamasamit Nattapong; Suthienkul Orasa; 鈴木 定彦, 日本細菌学雑誌, 75, 1, 60, 60, 2020年01月
  日本細菌学会, 英語
• Detection of quinolone resistance determinants in E. coli from food animals in the Philippines(和訳中)
  Belotindos Lawrence; Mingala Claro; Villanueva Marvin; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 75, 1, 64, 64, 2020年01月
  日本細菌学会, 英語
• Existence of extracellular DNA in pathogenic mycobacteria and its role in mycobacterial physiology(和訳中)
  イリノフ・アレクサンドル; シャバン・アミナ; 袴田 真理子; 西山 晃史; 尾関 百合子; 福島 由華里; 中島 千絵; 立石 善隆; 鈴木 定彦; 松本 壮吉, 日本細菌学雑誌, 75, 1, 74, 74, 2020年01月
  日本細菌学会, 英語
• Emergence of vanD5-type vancomycin-resistant Enterococcus faecium via horizontal genomic transfer(和訳中)
  佐藤 豊孝; 和田 崇之; 福島 由華里; 中島 千絵; 鈴木 定彦; 高橋 聡; 横田 伸一, 日本細菌学雑誌, 75, 1, 100, 100, 2020年01月
  日本細菌学会, 英語
• NADPH再生系を内包するハイブリッド型アゾレダクターゼの開発
  堀内正隆; 永田崇; 片平正人; 小橋川敬博; 鈴木定彦; 落合正則, 第42回日本分子生物学会年会, 福岡国際会議場(福岡)2019.12.3-6, 42nd, 2019年12月
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 免疫チェックポイント分子Programmed death‐ligand 1(PD‐L1)を標的とする抗体薬による免疫療法が奏功した肺転移のある口腔内悪性黒色腫の犬の1例
  竹内寛人; 前川直也; 今内覚; 高木哲; 細谷謙次; 賀川由美子; 岡川朋弘; 鈴木定彦; 鈴木定彦; 山本啓一; 山本啓一; 村田史郎; 大橋和彦, 北海道獣医師会雑誌, 63, 8, 343, 343, 2019年08月09日
  (公社)北海道獣医師会, 日本語
• Direct detection of Mycobacterium tuberculosis in clinical samples by a dry methyl green loop-mediated isothermal amplification (LAMP) method
  Jeewan Thapa; Bhagwan Maharjan; Meena Malla; Yukari Fukushima; Ajay Poudel; Basu Dev Pandey; Kyoko Hyashida; Stephen V. Gordon; Chie Nakajima; Yasuhiko Suzuki, Tuberculosis, 117, 1, 6, 2019年07月01日, ［国際誌］
  英語
• 非結核性抗酸菌(MAC及びM.kansasii)の新規核酸増幅検査法の開発
  橋本章司; 新井剛; 高田宏宗; 韓由紀; 田村嘉孝; 永井崇之; 松井謹; 小野原健一; 吉多仁子; 中島千絵; 鈴木定彦, 結核, 94, 3, 311, 2019年03月15日
  日本語
• One Healthアプローチを通じた細菌性感染症の制御 病原性微生物の特性に関する新規分析法の開発(Development of new methods for the characterization of bacterial pathogens)
  中島 千絵; 鈴木 定彦; Thapa Jeewan, 日本細菌学雑誌, 74, 1, 5, 5, 2019年03月
  日本細菌学会, 英語
• スリランカ、Kandyにおける結核菌の集団構成 欧米系統の優勢(Population structure of Mycobacterium tuberculosis in Kandy, Sri Lanka: Dominance of Euro-American lineage)
  Mendis Charitha; Ratnatunga Champa; Thevanesam Vasanthi; Kumara Athula; Wickramasinghe Susiji; Madagedara Dushantha; Gamage Chandika; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 45, 45, 2019年03月
  日本細菌学会, 英語
• タイ国の屠殺場と市場から分離されたMRSAの分子的分析(Molecular analysis of MRSA isolates from slaughterhouses and markets in Thailand)
  Tanomsridachchai Wimonrat; Changkaew Kanjana; Changkwanyeun Ruchirada; 中島 千絵; Suthienkul Orasa; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 45, 45, 2019年03月
  日本細菌学会, 英語
• ループ仲介等温増幅法を用いた人畜共通感染性結核の迅速検出法(Rapid detection of zoonotic tuberculosis using Loop mediated isothermal amplification)
  Kapalamula Thoko; Thapa Jeewan; 中島 千絵; Akapelwa Mwangala; Gordon Stephen V; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 67, 67, 2019年03月
  日本細菌学会, 英語
• ループ仲介等温増幅法を用いたMycobacterium aviumの迅速検出ツールの開発(Development of a rapid detection tool for Mycobacterium avium using Loop-mediated isothermal Amplification)
  Akapelwa Mwangala; Kapalamula Thoko; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 68, 68, 2019年03月
  日本細菌学会, 英語
• ザンビア、Lusakaで分離された結核菌のpyrazinamide耐性の分析(Determination of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia)
  Bwalya Precious; Yamaguchi Tomoyuki; Mulundu Georgina; 中島 千絵; Mbulo Grace; Solo Eddie; Fukushima Yukari; Kasakwa Kunda; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 79, 79, 2019年03月
  日本細菌学会, 英語
• バイオフィルム中における大腸菌persister制御のためのトスフロキサシンとSOS反応阻害剤の可能性
  臼井 優; 横尾 勇人; 田村 豊; 中島 千絵; 鈴木 定彦; Jean-Marc Ghigo; Beloin Christophe, 日本細菌学雑誌, 74, 1, 80, 80, 2019年03月
  日本細菌学会, 日本語
• WQ-3810はMycobacterium lepraeのDNAジャイレースに対して強力な阻害活性を示した(WQ-3810 showed strong inhibitory activity against Mycobacterium leprae DNA gyrase)
  Park JongHoon; 山口 智之; 大内 勇樹; Kim Hyun; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 82, 82, 2019年03月
  日本細菌学会, 英語
• SOS応答を標的とした薬剤耐性制御物質としてのプロテアーゼ阻害剤の可能性
  横尾 勇人; 臼井 優; 鈴木 定彦; 中島 千絵; 田村 豊, 日本細菌学雑誌, 74, 1, 99, 99, 2019年03月
  日本細菌学会, 日本語
• プラスミドにコードされるキノロン耐性タンパク質QnrB19とサルモネラDNAジャイレースの相互作用(Interaction of the plasmid-encoded quinolone resistance protein QnrB19 with salmonella DNA gyrases)
  Pachanon Ruttana; 小出 健太郎; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 99, 99, 2019年03月
  日本細菌学会, 英語
• タイ水圏環境中から分離された多剤耐性大腸菌の遺伝子学的特徴(Genomic characterization of multidrug resistant E. coli in environmental water in Thailand)
  角田 梨紗; 中島 千絵; 臼井 優; 田村 豊; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 100, 100, 2019年03月
  日本細菌学会, 英語
• キノロン耐性結核菌におけるFitness Costおよびその補完機構(Fitness Cost and Compensatory Mechanism in Fluoroquinolone Resistance Mycobacterium tuberculosis)
  大内 勇樹; 向井 徹; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 101, 101, 2019年03月
  日本細菌学会, 英語
• フィリピンの食用動物から分離されたE.coliとSalmonellaにおけるキノロン耐性の決定因子(Quinolone Resistance Determinants in E. coli and Salmonella from Food animals in the Philippines)
  Belotindos Lawrence; Mingala Claro; Villanueva Marvin; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 129, 129, 2019年03月
  日本細菌学会, 英語
• Mycobacterium lepraeのDNAジャイレースの機能的分析と細菌増殖と生存における役割(Functional analysis of Mycobacterium leprae DNA gyrase and its role in bacterial growth and survival)
  金 玄; 福富 康夫; 中島 千絵; Kim Youn Uck; 森 茂太郎; 柴山 恵吾; 中田 登; 鈴木 定彦, 日本細菌学雑誌, 74, 1, 121, 121, 2019年03月
  日本細菌学会, 英語
• 免疫学的解析を基盤とした動物用創薬研究
  今内 覚; 岡川朋弘; 前川直也; 中島千絵; 鈴木定彦; 山本啓一; 戸田幹洋; 村田史郎; 大橋和彦, 臨床獣医, 37, 3, 37, 41, 2019年03月, ［招待有り］
  (株)緑書房, 日本語, 記事・総説・解説・論説等（学術雑誌）
• バイオフィルム中における大腸菌persister制御のためのトスフロキサシンとSOS反応阻害剤の可能性
  臼井優; 横尾勇人; 田村豊; 中島千絵; 鈴木定彦; JEAN-MARC Ghigo; BELOIN Christophe, 日本細菌学雑誌(Web), 74, 1, 2019年
• SOS応答を標的とした薬剤耐性制御物質としてのプロテアーゼ阻害剤の可能性
  横尾勇人; 臼井優; 鈴木定彦; 中島千絵; 田村豊, 日本細菌学雑誌(Web), 74, 1, 2019年
• 「人獣共通感染症研究―ワンヘルスの取り組みと動物実験の役割―」(II)ワンヘルスの理念と人獣共通感染症制圧への取り組み:ザンビアでの活動
  鈴木定彦, Labio 21, 75, 14‐18, 2019年01月01日
  日本語
• 結核・非結核性抗酸菌症―エキスパートが教える 実臨床に役立つ最新知見―結核・非結核性抗酸菌症の基礎研究 結核菌の薬剤耐性獲得
  山口智之; 中島千絵; 鈴木定彦, 呼吸器ジャーナル, 66, 4, 650‐656, 667, 2018年11月01日
  (株)医学書院, 日本語
• 動物難治性疾病に対する創薬研究
  今内 覚; 岡川朋弘; 前川直也; 中島千絵; 鈴木定彦; 山本啓一; 戸田幹洋; 村田史郎; 大橋和彦, MPアグロジャーナル, 35, 10, 22, 25, 2018年10月, ［招待有り］
  MPアグロ, 日本語, 記事・総説・解説・論説等（学術雑誌）
• ウシCytotoxic T‐lymphocyte antigen‐4(CTLA‐4)の機能解析および慢性感染症における発現解析
  渡慧; 今内覚; 岡川朋弘; 前川直也; 後藤伸也; 佐治木大和; 村田史郎; 鈴木定彦; 大橋和彦, 日本獣医学会学術集会講演要旨集, 161st, 340, 340, 2018年08月21日
  (公社)日本獣医学会, 日本語
• 肺転移のある悪性黒色腫罹患犬に対するPD‐L1を標的とした抗体薬の治療効果
  前川直也; 今内覚; 高木哲; 細谷謙次; 賀川由美子; 岡川朋弘; 和泉雄介; 出口辰弥; 鈴木定彦; 山本啓一; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 161st, 429, 429, 2018年08月21日
  (公社)日本獣医学会, 日本語
• イヌCytotoxic T‐lymphocyte antigen‐4(CTLA‐4)を標的としたバイオ医薬品の開発に向けた基礎的検討
  石原悠太郎; 今内覚; 岡川朋弘; 前川直也; 鈴木定彦; 大田寛; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 161st, 430, 430, 2018年08月21日
  (公社)日本獣医学会, 日本語
• Mycoplasma bovis感染症における免疫抑制機序の解析
  後藤伸也; 今内覚; 岡川朋弘; 前川直也; 佐治木大和; 渡慧; 樋口豪紀; 小岩政照; 田島誉士; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 161st, 342, 342, 2018年08月21日
  (公社)日本獣医学会, 日本語
• チミジル酸合成酵素遺伝子過剰発現によるBCGの増殖速度の促進とその機序の解明
  大原直也; 大原直也; 和田崇之; 阿戸学; 鈴木定彦, 結核, 93, 4, 290, 2018年04月15日
  日本語
• ポリマー圧電素子を用いた病原体特異的分子検出用バイオセンサの開発―分子識別素子の設計―
  武田真理子; 平田孝道; 黒岩崇; 中島千絵; 鈴木定彦; 宗像文男, Chemical Sensors, 34, Supplement A, 37‐39, 39, 2018年03月09日
  電気化学会化学センサ研究会, 日本語
• ポリマー圧電素子を用いた病原体特異的分子検出用バイオセンサの開発―検知用バイオセンサの試作と評価―
  武田真理子; 平田孝道; 黒岩崇; 中島千絵; 鈴木定彦; 宗像文男, 電気化学会大会講演要旨集(CD-ROM), 85th, ROMBUNNO.PS‐93, 2018年02月23日
  日本語
• ポリマー圧電素子を用いた病原体特異的分子検出用バイオセンサの開発―分子識別素子の設計―
  武田真理子; 平田孝道; 黒岩崇; 中島千絵; 鈴木定彦; 宗像文男, 電気化学会大会講演要旨集(CD-ROM), 85th, ROMBUNNO.1B13, 2018年02月23日
  日本語
• ミャンマーにおける北京型結核菌の考察(Insight into the Beijing genotype Mycobacterium tuberculosis in Myanmar)
  Lai Lai San; Nan Aye Thida Oo; Wah Wah Aung; Khin Saw Aye; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 50, 50, 2018年02月
  日本細菌学会, 英語
• GyrAに新規アミノ酸置換を有するSalmonella enteritidisの全ゲノムシークエンス分析(Whole genome sequencing of Salmonella Enteritidis having a novel amino acid substitution on GyrA)
  小出 健太郎; Utrarachkil Fuangfa; Suthienkul Orasa; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 51, 51, 2018年02月
  日本細菌学会, 英語
• ミャンマーで分離された結核菌における薬剤耐性関連変異の同定(Detection of drug-resistant associated mutations in Mycobacterium tuberculosis isolates of Myanmar)
  Nan Aye Thida Oo; Lai Lai San; Khin Saw Aye; Wah Wah Aung; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 55, 55, 2018年02月
  日本細菌学会, 英語
• メチルグリーンを用いたループ仲介等温増幅法による結核の診断(Diagnosis of tuberculosis by methyl green based loop-mediated isothermal amplification method)
  Thapa Jeewan; Maharjan Bhagwan; 福島 由華里; Malla Meena; Poudel Ajay; Pandey Basu Dev; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 64, 64, 2018年02月
  日本細菌学会, 英語
• BCGの増殖率促進に関与する遺伝子の調査(Investigation of genes involved in promoting the growth rate of BCG)
  竜門 亜矢子; 中山 真彰; 和田 崇之; 橘 理人; 阿戸 学; 中島 千絵; 鈴木 定彦; 小崎 弘貴; 大原 直也, 日本細菌学雑誌, 73, 1, 68, 68, 2018年02月
  日本細菌学会, 日本語
• Ofloxancin耐性Mycobacterium lepraeのDNAジャイレースに対するWQ-3810の阻害活性(Inhibitory activity of WQ-3810 against DNA gyrases of ofloxacin-resistant Mycobacterium leprae)
  Park JongHoon; 山口 智之; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 136, 136, 2018年02月
  日本細菌学会, 英語
• タイの水圏環境における薬剤耐性と残留抗菌薬濃度との関係
  角田 梨紗; 臼井 優; 高田 秀重; 中島 千絵; 鈴木 定彦; 田村 豊, 日本細菌学雑誌, 73, 1, 139, 139, 2018年02月
  日本細菌学会, 日本語
• フルオロキノロン耐性で非PGG3 Mycobacterium tuberculosisのDNAジャイレースの特徴(Characterization of DNA gyrase in fluoroquinolone-resistant non-PGG3 Mycobacterium tuberculosis)
  大内 勇樹; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 73, 1, 139, 139, 2018年02月
  日本細菌学会, 英語
• BCGの増殖速度の促進における遺伝子の調査
  竜門亜矢子; 中山真彰; 中山真彰; 和田崇之; 橘理人; 阿戸学; 中島千絵; 鈴木定彦; 小崎弘貴; 大原直也; 大原直也, 日本細菌学雑誌(Web), 73, 1, 2018年
• タイの水圏環境における薬剤耐性と残留抗菌薬濃度との関係
  角田梨紗; 臼井優; 高田秀重; 中島千絵; 鈴木定彦; 田村豊, 日本細菌学雑誌(Web), 73, 1, 2018年
• NADPH再生系を伴ったアゾレダクターゼによるアゾ染料分解反応のNMR解析
  堀内正隆; 永田崇; 片平正人; 小橋川敬博; 鈴木定彦; 落合正則, 日本分子生物学会年会プログラム・要旨集(Web), 41st, ROMBUNNO.3P‐0752 (WEB ONLY), 2018年
  日本語
• 牛マイコプラズマ感染症における免疫抑制機序の解明
  後藤伸也; 今内覚; 岡川朋弘; 西森朝美; 前川直也; 樋口豪紀; 小岩政照; 田島誉士; 小原潤子; 加藤幸成; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 160th, 370, 370, 2017年08月30日
  (公社)日本獣医学会, 日本語
• Multiplex PCR法による鶏肉からの薬剤耐性カンピロバクターの迅速検出法
  松井有優; 臼井優; 中島千絵; 小野崎正修; 鈴木定彦; 田村豊, 日本獣医学会学術集会講演要旨集, 160th, 415, 2017年08月30日
  日本語
• PD‐L1を標的としたイヌ用キメラ抗体医薬の作製と悪性黒色腫および未分化肉腫罹患犬における抗腫瘍効果の検討
  前川直也; 今内覚; 高木哲; 賀川由美子; 岡川朋弘; 西森朝美; 池渕良洋; 和泉雄介; 出口辰弥; 加藤幸成; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 160th, 460, 460, 2017年08月30日
  (公社)日本獣医学会, 日本語
• BLV感染症をモデルとした抗ウシPD‐L1キメラ抗体の臨床応用試験
  西森朝美; 今内覚; 岡川朋弘; 前川直也; 池渕良洋; 後藤伸也; 佐治木大和; 鈴木定彦; 小原潤子; 小笠原諭; 加藤幸成; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 160th, 370, 370, 2017年08月30日
  (公社)日本獣医学会, 日本語
• Novel Mycobacterium avium Complex Species Isolated From Black Wildebeest (Connochaetes gnou) in South Africa
  P. N. Kabongo-Kayoka; C. L. Obi; C. Nakajima; Y. Suzuki; T. Hattori; J. N. Eloff; J. Wright; N. Mbelle; L. J. McGaw, TRANSBOUNDARY AND EMERGING DISEASES, 64, 3, 929, 937, 2017年06月
  英語
• らい菌のキノロン系抗菌薬耐性の獲得に伴うDNAジャイレース活性変化の解析
  鈴木定彦; 山口智之; 中島千絵, Japanese Journal of Leprosy, 86, 1, 50, 2017年04月22日
  日本語
• ポリマー圧電素子を用いたDNA検出用バイオセンサの検知特性
  武田真理子; 矢萩洸貴; 杉山龍男; 平田孝道; 中島千絵; 鈴木定彦; 宗像文男, Chemical Sensors, 33, Supplement A, 58‐60, 60, 2017年03月25日
  電気化学会化学センサ研究会, 日本語
• ポリマー圧電素子を用いたDNA検出用バイオセンサの検知特性
  武田真理子; 矢萩洸貴; 杉山龍男; 平田孝道; 中島千絵; 鈴木定彦; 宗像文男, 電気化学会大会講演要旨集(CD-ROM), 84th, ROMBUNNO.2U03, 60, 2017年03月17日
  電気化学会化学センサ研究会, 日本語
• 忘れてはいけない人獣共通感染症 8.結核と非結核性抗酸菌症
  鈴木定彦; 中島千絵; 鈴木定彦; 中島千絵, 化学療法の領域, 33, 3, 411‐418, 2017年02月25日
  日本語
• ヨーネ菌組換え抗原タンパクに対する実験感染牛の血清抗体反応性
  松葉 隆司; 永田 礼子; 川治 聡子; 中島 千絵; 鈴木 定彦; 藤井 潤, 日本細菌学雑誌, 72, 1, 117, 117, 2017年02月
  日本細菌学会, 日本語
• Impact of T95S and D668G in GyrA of Mycobacterium tuberculosis on compensatory evolution(和訳中)
  大内 勇樹; 小出 健太郎; 山口 智之; 朴 鐘勲; 金 玄; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 131, 131, 2017年02月
  日本細菌学会, 英語
• Antibacterial activity of WQ-3810, a novel fluoroquinolone, against Salmonella Typhimurium(和訳中)
  小出 健太郎; コングソイ・シリポン; 大内 勇樹; 朴 鐘勲; 山口 智之; チャンクワイエン・ルチラダ; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 135, 135, 2017年02月
  日本細菌学会, 英語
• らい菌及び結核菌由来DNAジャイレースの性状解析
  金 玄; 福富 康夫; 中島 千絵; 松岡 正典; 森 茂太郎; 柴山 恵吾; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 136, 136, 2017年02月
  日本細菌学会, 日本語
• Analysis of streptomycin-resistance associating genes in Mycobacterium tuberculosis in Nepal(和訳中)
  シュレスタ・ディプティ; マハージャン・バグワン; ウーナン・エーティダ; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 141, 141, 2017年02月
  日本細菌学会, 英語
• Molecular diversity of Mycobacterium tuberculosis in Kandy, Sri Lanka: Insight to Beijing genotype(和訳中)
  メンディス・チャリサ; Ratnatunga Champa; Thevanesam Vasanthi; Kumara Athula; Wickramasinghe Susiji; Madegedara Dushantha; Gamage Chandika; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 167, 167, 2017年02月
  日本細菌学会, 英語
• ヨーネ菌組換え抗原タンパクに対する実験感染牛の血清抗体反応性
  松葉 隆司; 永田 礼子; 川治 聡子; 中島 千絵; 鈴木 定彦; 藤井 潤, 日本細菌学雑誌, 72, 1, 117, 117, 2017年02月
  日本細菌学会, 日本語
• らい菌及び結核菌由来DNAジャイレースの性状解析
  金 玄; 福富 康夫; 中島 千絵; 松岡 正典; 森 茂太郎; 柴山 恵吾; 鈴木 定彦, 日本細菌学雑誌, 72, 1, 136, 136, 2017年02月
  日本細菌学会, 日本語
• ヨーネ菌組換え抗原タンパクに対する実験感染牛の血清抗体反応性
  松葉隆司; 永田礼子; 川治聡子; 中島千絵; 鈴木定彦; 藤井潤, 日本細菌学雑誌(Web), 72, 1, 117(J‐STAGE), 2017年
  日本語
• らい菌及び結核菌由来DNAジャイレースの性状解析
  KIM Hyun; 福富康夫; 中島千絵; 松岡正典; 森茂太郎; 柴山恵吾; 鈴木定彦, 日本細菌学雑誌(Web), 72, 1, 136(J‐STAGE), 2017年
  日本語
• 種内相互組み換えによって促進される鳥型結核菌の地域適応
  矢野大和; 丸山史人; 西内由紀子; 中川一路; 中島千絵; 鈴木定彦; 岩本朋忠, 日本ゲノム微生物学会年会要旨集, 11th, 57, 2017年
  日本語
• 人獣共通感染症としての結核
  中島千絵; 鈴木定彦, 獣医疫学雑誌, 20, 2, 101‐104, 104, 2016年12月20日
  人獣共通感染症としての観点から人型結核菌(M. tuberculosis)を見た場合，状況は上述の人における様相とはかなり異なる。毎年1千万人前後の新患を出し，世界人口の1/3が既に結核菌に感染していると言われているが，この人における重度の蔓延状態と比べると，動物におけるM. tuberculosisによる感染報告は恐ろしく少ない。霊長類や一部の例外を除いて，患者と密な接触のあった動物(牛，犬等)において稀に報告がある程度である。例外的にエチオピアにおいて牛群の集団感染が報告されているが，これはこの地域特有の人と牛との濃厚な接触習慣により，個々の牛が人から感染を受けているものと考えられる。これらに対して，大きな例外となるのが人に飼育されているアジアゾウである。最初はアメリカのサーカスや動物園で飼育されているゾウで報告され，その後，タイやネパール等のアジアゾウ本来の分布域内の飼育施設において多数の感染例が報告される様になった。我々がネパールの国立公園において行った調査では，これらのゾウ感染株はM. tuberculosisであり，ネパール患者から得られる株特有の遺伝子上の変異を持っていたことから，感染源は人間で，恐らくは日々密接な係りを持っている飼育係と考えられた。何故，アジアゾウのみから多数のM. tuberculosisによる結核発症例が報告されるのかは不明だが，菌の遅い増殖速度を考えると，動物のM. tuberculosisに対する感受性等の要因の他に，ゾウが人間並みに長命であることも関与しているかもしれない。以上より，M. tuberculosisは基本的に人の結核起因菌であり，高度に人に順化していると考えられる。世界の牛結核発生状況は人結核と趣が異なり，人結核がほとんど見られなくなった西欧諸国やニュージーランド等で高度の蔓延が観察される。また，今一つ異なる特長は，世界的に蔓延している菌株の遺伝的特徴が非常に良く似ている点である(M. tuberculosisでは地域によって多様性が見られる)。有名な例はEulと呼ばれる株で，この菌株の特徴を持った菌がアメリカ大陸やオーストラリア，ニュージーランド，南アフリカなどで分離される。型別情報からこれらの起源を辿ると，元々はイギリスやアイルランドで蔓延していた株であることが判る。これは，近代以降にこれらの国から牛が，主として大英帝国関連の国々へ輸出された名残であると推測される。南ア以外のアフリカ諸国では，また別のタイプの牛結核菌が分離されるが，これらも元を辿るとフランス，オランダ等の由来であることが示唆され，アフリカの牛結核はほぼヨーロッパが起源となっている。, 獣医疫学会, 日本語
• Collectin CL-P1 is involved in C-reactive protein-mediated complement activation
  Nitai Roy; Katsuki Ohtani; Yasuyuki Matsuda; Kenichiro Mori; Insu Hwang; Yasuhiko Suzuki; Norimitsu Inoue; Nobutaka Wakamiya, IMMUNOBIOLOGY, 221, 10, 1215, 1215, 2016年10月
  英語, 研究発表ペーパー・要旨（国際会議）
• マイクロアレイ技術を応用した薬剤耐性カンピロバクターの迅速検出法(CAMERA法)
  臼井 優; 舘野 翔; 田勢 準也; 田村 豊; 中島 千絵; 鈴木 定彦; 小野崎 正修; 大曽根 司郎, グリーンテクノ情報, 12, 2, 14, 17, 2016年09月
  NPO法人グリーンテクノバンク, 日本語
• ウシCytotoxic T‐lymphocyte antigen‐4(CTLA‐4)の機能解析と特異抗体の樹立
  渡慧; 今内覚; 前川直也; 岡川朋弘; 西森朝美; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 159th, 365, 365, 2016年08月30日
  (公社)日本獣医学会, 日本語
• 家畜における免疫チェックポイント関連因子の遺伝子比較解析とウシ用抗体を用いた動物種横断的研究
  野島裕太郎; 今内覚; 西森朝美; 前川直也; 岡川朋弘; 森康行; 賀川由美子; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 159th, 364, 364, 2016年08月30日
  (公社)日本獣医学会, 日本語
• ウシ腫瘍壊死因子(TNF‐α)デコイレセプターによる新規抗炎症剤の開発
  藤澤宗太郎; 今内覚; 岡川朋弘; 西森朝美; 前川直也; 村田史郎; 鈴木定彦; 大橋和彦, 日本獣医学会学術集会講演要旨集, 159th, 364, 364, 2016年08月30日
  (公社)日本獣医学会, 日本語
• ウシ用腸溶性生菌剤カプセルが腸内細菌相に与える影響
  瀬山智博; 平康博章; 吉田弦; 大沼愛子; 邱永晋; 中島千絵; 笠井浩司; 鈴木定彦, 日本畜産学会大会講演要旨, 121st, 237, 2016年03月27日
  日本語
• 感染症 現状の問題点と未来への展望 結核―人獣共通感染症の観点から
  鈴木定彦; 中島千絵, 臨床と微生物, 43, 2, 169‐173, 2016年03月25日
  日本語
• BCG thyXを用いた抗酸菌のPAS耐性機序の解析
  大原直也; 大原直也; 阿戸学; 鈴木定彦; 小林和夫, 結核, 91, 3, 325, 325, 2016年03月15日
  (一社)日本結核・非結核性抗酸菌症学会, 日本語
• Mycobacterium aviumの系統分岐に伴う大規模なゲノム構造の変化
  岩本 朋忠; 矢野 大和; 西内 由紀子; 有川 健太郎; 中島 千絵; 鈴木 定彦; 丸山 史人, 日本細菌学雑誌, 71, 1, 58, 58, 2016年02月
  日本細菌学会, 日本語
• ミャンマーで単離された北京型多剤耐性結核菌株のMIRU-VNTRを用いた判別法(MIRU-VNTR Typing of Beijing MDR-TB strains from Myanmar)
  Lai Lai San; Nan Aye Thida Oo; Wah Wah Aung; Khin Saw Aye; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 71, 1, 59, 59, 2016年02月
  日本細菌学会, 英語
• ミャンマーで単離されたストレプトマイシン耐性結核菌における変異の同定(Detection of mutations in streptomycin resistance Mycobacterium tuberculosis isolates from Myanmar)
  Nan Aye Thida Oo; Lai Lai San; Khin Saw Aye; Wah Wah Aung; Wah Wah; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 71, 1, 105, 105, 2016年02月
  日本細菌学会, 英語
• Mycobacterium lepraeのDNAジャイレースに対する新規の8-メトキシフルオロキノロンの阻害活性(Inhibitory activities of a new 8-methoxy fluoroquinolone against DNA gyrase of Mycobacterium leprae)
  山口 智之; 中島 千絵; 鈴木 定彦, 日本細菌学雑誌, 71, 1, 140, 140, 2016年02月
  日本細菌学会, 英語
• 抗酸菌のPAS耐性機序の解明 BCG thyX欠損株および過剰発現株の作製
  有村 友紀; 中山 真彰; 妹尾 昌紀; 田川 淳平; 阿戸 学; 中島 千絵; 鈴木 定彦; 中山 浩次; 小林 和夫; 大原 直也, 日本細菌学雑誌, 71, 1, 142, 142, 2016年02月
  日本細菌学会, 日本語
• 南アジアはMycobacterium orygisの風土病地域である(South Asia is an endemic region for Mycobacterium orygis)
  Thapa Jeewan; 中島 千絵; Rahim Zeaur; Paudel Sarad; Shah Yogendra; Maharian Bhagwan; Poudel Ajay; Gairhe Kamal Prasad; 坪田 敏男; 鈴木 定彦, 日本細菌学雑誌, 71, 1, 159, 159, 2016年02月
  日本細菌学会, 英語
• 東アジアの小型哺乳動物から分離されたレプトスピラの反復配列多型解析法による分子型別
  小泉信夫; 泉谷秀昌; 慕蓉蓉; 岡野祥; 中島千絵; 鈴木定彦; 谷川力; 小松謙之; 吉松組子; 武藤(水谷)麻紀; 武藤(水谷)麻紀; 大西真, レプトスピラ・シンポジウム, 53rd, 5, 2016年
  日本語
• ザンビアにおける結核対策への貢献
  鈴木定彦; 鈴木定彦, 日本熱帯医学会大会プログラム抄録集, 56th, 30, 2015年12月04日
  日本語
• CAMERA法による野外サンプル(鶏肉及び鶏糞便)からの薬剤耐性カンピロバクターの迅速検出法
  臼井優; 中島千絵; 舘野翔; 田勢準也; 小野崎正修; 大曾根司朗; 鈴木定彦; 田村豊, 日本獣医学会学術集会講演要旨集, 158th, 363, 2015年08月30日
  日本語
• 新興・再興感染症と感染症対策 C.細菌 結核 終わらない脅威とその対策
  鈴木定彦; 中島千絵, 生体の科学, 66, 4, 335, 338, 2015年08月15日
  日本語
• らい菌のDNAジャイレースに対するキノロン系抗菌薬の阻害活性試験とその結果から考える結合様式
  山口智之; 中島千絵; 鈴木定彦, Jpn J Lepr, 84, 1, 26, 2015年05月25日
  日本語
• Inquisition of DNA gyrase genes on fluoroquinolone resistant clinical Mycobacterium avium isolates
  MENDA Conscillioah; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 191, 2015年02月25日
  英語
• Detection of loop-mediated isothermal amplification reaction by non-fluorescent leuco dyes
  THAPA Jeewan; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 200, 2015年02月25日
  英語
• Extended-spectrum beta-lactamases in Escherichia coli isolated from swine in Thailand
  CHANGKAEW Kanjana; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 190, 2015年02月25日
  英語
• Diversity of MIRU-VNTR among Mycobacterium tuberculosis Central Asian family isolates from Nepal
  SHAH Yogendra; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 208, 2015年02月25日
  英語
• Virulence factors and class 1 integrons in Vibrio parahaemolyticus from shrimp farming environment
  CHANGKWANYEUN Ruchirada; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 190, 2015年02月25日
  英語
• The selection of ciprofloxacin resistance in Salmonella Typhimurium exposed residue level in vitro
  KONGSOI Siriporn; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 190, 2015年02月25日
  英語
• Alteration opf Mycobacterium leprae DNA gyrase activity by mutations conferring quinolone resistance
  YAMAGUCHI Tomoyuki; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 191, 2015年02月25日
  英語
• Understanding the circulation of Leptospira among water buffaloes in an intensive farm setting
  VILLANUEVA Marvin; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 70, 1, 208, 2015年02月25日
  英語
• DNAアレイを応用した迅速・簡便な薬剤耐性カンピロバクター検出法の開発
  中島千絵; 臼井優; 田村豊; 鈴木定彦, 日本細菌学雑誌, 70, 1, 202, 2015年02月25日
  日本語
• 抗酸菌におけるパラアミノサリチル酸に対する新たな耐性機序の可能性
  ZHAO Na; 中山真彰; 関塚剛史; 黒田誠; 本田尚子; 阿戸学; 中島千絵; 鈴木定彦; 大原直也, 日本細菌学雑誌, 70, 1, 193, 2015年02月25日
  日本語
• 結核菌Rv0679cタンパク機能の解析
  松葉隆司; 中島千絵; 藤井潤; 鈴木定彦, 日本細菌学雑誌, 70, 1, 182, 2015年02月25日
  日本語
• ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 薬剤耐性獲得機構解明とその迅速感受性試験法開発への応用
  鈴木定彦; 中島千絵, ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 平成26年度 総括・分担研究報告書, 13, 17, 2015年
  日本語
• GRP‐tag化酵素を利用したアゾ染料分解システムの構築
  堀内正隆; 鈴木定彦; 落合正則, 日本生化学会大会(Web), 88th, 2P0907 (WEB ONLY), 2015年
  日本語
• 多剤耐性結核の分子疫学的解析,診断・治療法の開発に関する研究 スリランカ,ネパール,バングラデシュ,ミャンマーおよびタイとの結核研究ネットワーク活用による多剤耐性結核の分子疫学解析
  鈴木定彦, 多剤耐性結核の分子疫学的解析、診断・治療法の開発に関する研究 平成26年度 委託業務成果報告書, 44‐46, 2015年
  日本語
• H5N1インフルエンザウイルスに対する中和抗体を用いた受動免疫の感染防御効果
  吉田玲子; 伊藤靖; 七戸新太郎; 小笠原一誠; 日尾野隆大; 岡松正敏; 迫田義博; 喜田宏; LE Mai Quynh; 河岡義裕; 五十嵐学; 鈴木定彦; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 62nd, 234, 2014年10月31日
  日本語
• 結核研究からハンセン病研究へ:分子生物学的見地から
  鈴木定彦, Jpn J Lepr, 83, 2, 16, 2014年07月25日
  日本語
• らい菌にキノロン系抗菌薬耐性を与える酵素内アミノ酸置換がもたらすDNAジャイレース活性低下の解析
  山口智之; 中島千絵; 鈴木定彦, Jpn J Lepr, 83, 2, 47, 2014年07月25日
  日本語
• Mycobacterium tuberculosis complex genotypic lineages circulating in Egyptian population
  DIAB Hassan; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 69, 1, 144, 2014年02月25日
  英語
• High levels of OPN, IP-10 and neutrophilia in LAMP confirmed TB patients in Manila
  SHIRATORI Beata; SHIRATORI Beata; LEANO Susan; NAKAJIMA Chie; CHAGAN‐YASUTAN Haorile; NIKI Toshiro; SUZUKI Yasuhiko; TELAN Elisabeth; HATTORI Toshio, 日本細菌学雑誌, 69, 1, 140, 2014年02月25日
  英語
• Tuberculosis caused by Mycobacterium orygis in dairy cattle and captured monkeys in Bangladesh
  NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 69, 1, 141, 2014年02月25日
  英語
• Development of loop-mediated isothermal amplification method for detection of Legionella pneumophila
  CHANGKAEW Kanjana; SUZUKI Yasuhiko; NAKAJIMA Chie, 日本細菌学雑誌, 69, 1, 201, 2014年02月25日
  英語
• Isolation and characterization of Mycobacterium orygis from a deer in Nepal
  THAPA Jeewan; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 69, 1, 141, 2014年02月25日
  英語
• Impact of amino acid substitutions in GyrA affects quinolone resistance in Salmonella Typhimurium
  KONGSOI Siriporn; SUZUKI Yasuhiko; NAKAJIMA Chie, 日本細菌学雑誌, 69, 1, 196, 2014年02月25日
  英語
• Impact of mutations in DNA gyrase genes on fluoroquinolone resistance in Campylobacter jejuni
  CHANGKWANYEUN Ruchirada; KIM Hyun; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 69, 1, 196, 2014年02月25日
  英語
• Epidemiological study of leptospirosis among water buffalo (Bubalus bubalis) in the Philippines
  VILLANUEVA Marvin; KOIZUMI Nobuo; SUZUKI Yasuhiko; NAKAJIMA Chie, 日本細菌学雑誌, 69, 1, 240, 2014年02月25日
  英語
• Genotypic characterization of multidrug-resistant Mycobacterium tuberculosis isolated in Myanmar
  SUZUKI Yasuhiko; NAKAJIMA Chie, 日本細菌学雑誌, 69, 1, 199, 2014年02月25日
  英語
• 結核診断用LAMP法の改良
  松葉隆司; 中島千絵; 鈴木定彦, 日本細菌学雑誌, 69, 1, 202, 2014年02月25日
  日本語
• 結核菌DNAジャイレースにおけるキノロン耐性決定領域外に見出されたアミノ酸置換のキノロン剤耐性への影響(Clarification of correlation between mutants DNA GyrA and quinolone resistance in M. tuberculosis)
  金 玄; 横山 和正; 中島 千絵; 森 茂太郎; 柴山 恵吾; 鈴木 定彦, 日本細菌学雑誌, 69, 1, 199, 199, 2014年02月
  日本細菌学会, 英語
• サハラ以南アフリカにおけるエイズ・結核研究ネットワークの構築に関する研究
  鈴木定彦; 中島千絵, サハラ以南アフリカにおけるエイズ・結核研究ネットワーク構築に関する研究 平成25年度 総括・分担研究報告書, 6, 8, 2014年
  日本語
• 結核研究からハンセン病研究へ:分子生物学的見地から
  鈴木定彦; 山口智之; KIM Hyun; 横山和正; 中島千絵, Jpn J Lepr, 83, 3, 131, 137, 2014年
  Japanese Leprosy Association, 日本語
• ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 薬剤耐性獲得機構解明とその迅速感受性試験法開発への応用に関する研究
  鈴木定彦; 中島千絵, ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 平成25年度 総括・分担研究報告書, 15, 18, 2014年
  日本語
• レプトスピラ症患者の血漿および尿中のバイオマーカーの解析
  ホルロ; 中島千絵; 小泉信夫; 鈴木定彦; 服部俊夫, レプトスピラ・シンポジウム, 51st, 10, 2014年
  日本語
• 細菌の進化から考える抗菌薬耐性 10.結核菌の薬剤耐性
  鈴木定彦; 中島千絵, 化学療法の領域, 30, 1, 113, 121, 2013年12月25日
  日本語
• Collectin CL-P1 is an endocytosis and phagocytosis receptor using clathrin-dependent endocytosis pathway and clathrin-independent phagocytosis pathway
  N. Wakamiya; S. Jang; A. Fukuoh; K. Mori; Y. Suzuki; K. Ohtani, MOLECULAR IMMUNOLOGY, 56, 3, 301, 302, 2013年12月
  英語, 研究発表ペーパー・要旨（国際会議）
• 病原体特異的等温遺伝子増幅(LAMP)法によるピロリン酸の発生量をモニターするポータブルバイオセンサーの開発
  矢萩洸貴; 中島千絵; 黒岩崇; 杉山龍男; 鈴木定彦; 宗像文男, 電気学会ケミカルセンサ研究会資料, CHS-13, 1-15, 71, 74, 2013年08月08日
  日本語
• コレクチンCL-K1血中濃度測定ELISAシステムの樹立と日本人における正常値について
  吉崎 隆之; 大谷 克城; 本村 亘; 張 成宰; 北元 憲利; 森 健一郎; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 88, 2, 96, 96, 2013年04月01日
  著者最終原稿版, 日本語
• 結核菌DNAジャイレース上の菌系統特異的アミノ酸多型のキノロン剤耐性への影響
  金玄; 横山和正; 中島千絵; 鈴木定彦, Jpn J Lepr, 82, 1/2, 22, 22, 2013年04月01日
  日本語
• 結核菌DNAジャイレースにおけるキノロン耐性決定領域外に見出されたアミノ酸置換のキノロン剤耐性への影響
  金玄; 横山和正; 中島千絵; 鈴木定彦, Jpn J Lepr, 82, 1/2, 24, 24, 2013年04月01日
  日本語
• Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis from Asian Countries
  NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 68, 1, 217, 2013年02月25日
  英語
• Inhibition activity of quinolones against DNA gyrase of Campylobacter jejuni
  CHANGKWANYEUN Ruchirada; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 68, 1, 191, 2013年02月25日
  英語
• Amino acid substitutions in DNA gyrase B subunit confer Quinolone resistance on Mycobacterium leprae
  SUZUKI Yasuhiko; KIM Hyun; MUKAI Tetsu; NAKAJIMA Chie, 日本細菌学雑誌, 68, 1, 191, 2013年02月25日
  英語
• Antimicrobial Resistance and Class 1 Integrons in Escherichia coli Isolated from Shrimp Environment
  CHANGKAEW Kanjana; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 68, 1, 195, 2013年02月25日
  英語
• Salmonella Typhimurium DNA Gyrase and Its Interaction with Quinolones
  KONGSOI Siriporn; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 68, 1, 190, 2013年02月25日
  英語
• 結核の革新的な診断・治療及び対策の強化に関する研究 多様な研究シーズを想定した結核菌臨床分離株のゲノム情報集積
  和田崇之; 鈴木定彦; 中島千絵, 結核の革新的な診断・治療及び対策の強化に関する研究 平成24年度 総括・研究分担報告書, 106, 111, 2013年
  日本語
• ヒトMAC症由来Mycobacterium avium subsp.hominissuisの遺伝的多様性とゲノム構造解析
  岩本朋忠; 中西典子; 中島千絵; 有川健太郎; 鈴木定彦, 日本ゲノム微生物学会年会要旨集, 7th, 51, 2013年
  日本語
• サハラ以南アフリカにおけるエイズ・結核研究ネットワークの構築に関する研究
  鈴木定彦; 中島千絵, サハラ以南アフリカにおけるエイズ・結核研究ネットワーク構築に関する研究 平成24年度 総括・分担研究報告書, 15, 18, 2013年
  日本語
• ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 薬剤耐性獲得機構解明とその迅速感受性試験法開発への応用
  鈴木定彦; 松岡正典; 中島千絵, ハンセン病の予防法及び診断・治療法の開発・普及に関する研究 平成24年度 総括・分担研究報告書, 15, 20, 2013年
  日本語
• 国際共同基盤研究に応用する抗酸菌感染症研究の整備 薬剤耐性結核菌の迅速検出法
  鈴木定彦; 中島千絵, 国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成24年度 総括・分担研究報告書, 17, 22, 2013年
  日本語
• 組織におけるコレクチンCL-K1の生化学的検討
  大谷 克城; 本村 亘; 吉崎 隆之; 森 健一郎; 松田 泰幸; 黄 仁秀; ニタイ・ロイ; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 日本生化学会大会プログラム・講演要旨集, 85回, 3T16, 07, 2012年12月
  (公社)日本生化学会, 日本語
• サハラ以南アフリカにおけるエイズ・結核研究ネットワーク構築の試み
  服部俊夫; 鈴木定彦; 山岡昇司; 井戸栄治; 一瀬休生; 仲宗根正; 久保亨; 臼澤基紀; 垣本和宏; 福本学; 児玉栄一, 日本国際保健医療学会学術大会プログラム・抄録集, 27th, 123, 2012年11月02日
  日本語
• アカゲザルモデルを用いたエボラ出血熱に対する中和モノクローナル抗体の防御効果
  吉田玲子; MARZI Andrea; 宮本洋子; 石島麻理; 鈴木定彦; 五十嵐学; 中山絵里; 黒田誠; FELDMANN Heinz; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 199, 2012年10月31日
  日本語
• コレクチンCL‐K1のマウスおよびヒト組織における発現検討
  大谷克城; 本村亘; 吉崎隆之; 森健一郎; 松田泰幸; HWANG Insu; CHANDRA Roy; 吉田逸朗; 鈴木定彦; 若宮伸隆, 日本糖質学会年会要旨集, 31st, 123, 2012年08月31日
  日本語
• ウシの免疫抑制受容体PD‐1に対するモノクローナル抗体の作製および免疫活性化能の検討
  池渕良洋; 今内覚; 岡川朋弘; 横山和正; 中島千絵; 鈴木定彦; 村田史郎; 大橋和彦, 日本獣医学会学術集会講演要旨集, 154th, 233, 2012年08月31日
  日本語
• ゼブラフィッシュCL-P1の遺伝子クローニングとその機能解析
  福田 光子; 大谷 克城; 張 成宰; 吉崎 隆之; 森 健一郎; 本村 亘; 吉田 逸朗; 鈴木 定彦; 高後 裕; 若宮 伸隆, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 4, 178, 178, 2012年08月01日
  日本語
• コレクチンCL-K1の組織における発現検討
  大谷 克城; 本村 亘; 吉崎 隆之; 森 健一郎; 松田 泰幸; 黄 仁秀; ロイ・ニタイ; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 補体シンポジウム講演集, 49, 23, 23, 2012年08月
  (一社)日本補体学会, 日本語
• らい菌のDNAジャイレースの性状解析
  金玄; 横山和正; 中島千絵; 松岡正典; 向井徹; 福富康夫; 鈴木定彦, Jpn J Lepr, 81, 1/2, 46, 2012年04月01日
  日本語
• らい菌のDNAジャイレースBサブユニット上のアミノ酸置換とニューキノロン耐性
  横山和正; 金玄; 中島千絵; 松岡正典; 向井徹; 鈴木定彦, Jpn J Lepr, 81, 1/2, 48, 2012年04月01日
  日本語
• らい菌のDNAジャイレースAサブユニット上のアミノ酸置換とニューキノロン耐性
  横山和正; 金玄; 中島千絵; 松岡正典; 向井徹; 鈴木定彦, Jpn J Lepr, 81, 1/2, 47, 2012年04月01日
  日本語
• A New Loop-Mediated Isothermal Amplification Method for Detection of Leptospira spp. in Urine
  KOIZUMI Nobuo; OHNISHI Makoto; NAKAJIMA Chie; SUZUKI Yasuhiko, 日本細菌学雑誌, 67, 1, 126, 2012年02月25日
  英語
• 人獣共通感染拡症としての結核
  鈴木定彦, 日本獣医師会獣医学術学会年次大会講演要旨集, 2011, 146, 147, 2012年01月20日
  日本語
• 海外から輸入される多剤耐性結核に関する研究 黒竜江省で収集した結核菌の分子疫学的解析
  服部俊夫; 凌虹; 鈴木定彦; 中島千絵, 海外から輸入される多剤耐性結核に関する研究 平成23年度 総括・分担研究報告書, 88, 90, 2012年
  日本語
• サハラ以南アフリカにおけるエイズ・結核研究ネットワークの構築に関する研究 ザンビアにおける結核菌の分子疫学的解析
  鈴木定彦; 中島千絵, サハラ以南アフリカにおけるエイズ・結核研究ネットワーク構築に関する研究 平成23年度 総括・分担研究報告書, 6, 8, 2012年
  日本語
• Loop‐mediated isothermal amplification法による尿からの簡便なレプトスピラ検出法
  小泉信夫; 中島千絵; 春成常仁; 谷川力; 常盤俊大; 内村江利子; 古谷徳次郎; MINGALA Claro Niegos; VILLANUEVA Marvin Ardeza; 大西真; 鈴木定彦, レプトスピラ・シンポジウム, 49th, 7, 2012年
  日本語
• 人獣共通感染症の克服に向けて 結核
  鈴木定彦; 松葉隆司; 中島千絵, 最新医学, 66, 12, 2689, 2696, 2011年12月10日
  日本語
• CORRELATION BETWEEN BEIJING GENOTYPE FAMILY AND THE ENVELOPE PROTEIN IN MYCOBACTERIUM TUBERCULOSIS
  MATSUBA Takashi; NAKAJIMA Chie; TAMARU Aki; SIDDIQI Umme R; HATTORI Toshio; RAHIM Zeaur; POUDEL Ajay; PANDEY Basu D; PANDEY Basu D; SUZUKI Yasuhiko, 日本細菌学雑誌, 66, 2-3, 426, 2011年10月31日
  英語
• コレクチンCL-K1のヒト血中濃度
  大谷 克城; 吉崎 隆之; 森 健一郎; 本村 亘; 松田 泰幸; 黄 仁秀; 吉田 逸朗; 金 然旭; 鈴木 定彦; 若宮 伸隆, 補体シンポジウム講演集, 48, 31, 31, 2011年09月
  (一社)日本補体学会, 日本語
• コレクチンCL-K1の機能について
  大谷 克城; 吉崎 隆之; 森 健一郎; 本村 亘; 黄 仁秀; 吉田 逸朗; 金 然旭; 鈴木 定彦; 若宮 伸隆, 日本生化学会大会プログラム・講演要旨集, 84回, 4T8a, 11, 2011年09月
  (公社)日本生化学会, 日本語
• 鳥取大学におけるバイオハザード対策用クラスIIキャビネットの維持管理とその発展途上国への応用
  松葉隆司; 甲斐政親; 飯塚昌; 鈴木定彦, 空気清浄, 49, 2, 53, 58, 2011年07月31日
  日本空気清浄協会, 日本語
• コレクチンCL‐P1のリガンド認識ドメインについての解析
  森健一郎; 大谷克城; JANG SeongJae; KIM YounUc; 本村亘; HWANG Insu; 吉田逸朗; 鈴木定彦; 若宮伸隆, 日本糖質学会年会要旨集, 30th, 73, 2011年06月27日
  日本語
• コレクチンCL‐K1の糖鎖特異性と機能解析
  大谷克城; 吉崎隆之; 森健一郎; 本村亘; HWANG Insu; 吉田逸朗; KIM YounUck; 鈴木定彦; 若宮伸隆, 日本糖質学会年会要旨集, 30th, 31, 2011年06月27日
  日本語
• 結核菌のニューキノロン高度耐性獲得機構
  金玄; 横山和正; 中島千絵; 鈴木定彦, Jpn J Lepr, 80, 2, 151, 2011年04月01日
  日本語
• 新たな等温増幅法による結核菌群菌の検出
  中島千絵; 鈴木定彦, 結核, 86, 3, 343, 2011年03月15日
  日本語
• オホーツクと南極海で採取した流氷における重金属濃度と金属耐性遺伝子の検出
  能田淳; 登坂唯香; 中島千絵; 大久保寅彦; 石原加奈子; 鈴木定彦; 伊村智; 田村豊, 日本獣医学会学術集会講演要旨集, 151st, 248, 2011年03月01日
  日本語
• 輸入感染症としての多剤耐性結核の対策・制御に関する研究 黒竜江省の結核菌解析に関する研究
  服部俊夫; 凌虹; 鈴木定彦, 輸入感染症としての多剤耐性結核の対策・制御に関する研究 平成22年度 総括・分担研究報告書, 81, 85, 2011年
  日本語
• 輸入感染症としての多剤耐性結核の対策・制御に関する研究[VI]潜在性結核の検出にかかわるT細胞機能と黒竜江省の結核菌解析
  服部俊夫; 凌虹; 鈴木定彦, 輸入感染症としての多剤耐性結核の対策・制御に関する研究 平成20-22年度 総合研究報告書, 96, 101, 2011年
  日本語
• 国際共同基盤研究に応用する抗酸菌感染症研究の整備 薬剤耐性結核菌の迅速検出法
  鈴木定彦; 中島千絵, 国際共同基盤研究に応用する抗酸菌感染症研究の整備 平成22年度 総括・分担研究報告書, 21, 25, 2011年
  日本語
• コレクチンCL‐K1の機能とヒト血中濃度について
  大谷克城; 吉崎隆之; 森健一郎; 本村亘; 松田泰幸; HWANG Insu; 吉田逸朗; KIM Younuck; 鈴木定彦; 若宮伸隆, 日本分子生物学会年会プログラム・要旨集(Web), 34th, WEB ONLY 2T8A-2, 2011年
  日本語
• らい菌および結核菌のニューキノロン耐性獲得機構と耐性菌迅速鑑別法
  KIM Hyun; 鈴木晴香; 松岡正典; 松葉隆司; 横山和正; 中島千絵; 鈴木定彦, Jpn J Lepr, 80, 1, 17, 27, 2011年, ［国内誌］
  1, 英語
• [Envelope structure and components of Mycobacterium tuberculosis].
  Matsuba T; Nakajima C; Suzuki Y, Nihon saikingaku zasshi. Japanese journal of bacteriology, 65, 3, 355, 368, 2010年12月, ［査読有り］, ［国内誌］
  2-4, 日本語
• 地球規模課題対応国際科学技術協力事業 結核及びトリパノソーマ症の診断法と治療薬開発
  鈴木定彦; 飯塚昌; 大栗博毅; 杉本千尋, 環境科学会誌, 23, 6, 522, 529, 2010年11月30日
  環境科学会, 日本語
• コレクチンCL-K1の機能解析
  大谷 克城; 吉崎 隆之; 森 健一郎; 本村 亘; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 補体シンポジウム講演集, 47, 22, 22, 2010年09月
  (一社)日本補体学会, 日本語
• 結核菌のニューキノロン高度耐性獲得機構
  金玄; 中島千絵; 鈴木定彦, Jpn J Lepr, 79, 2, 140, 2010年04月01日
  日本語
• 人獣共通感染症としての結核
  鈴木定彦; 松葉隆司; 中島千絵, 結核, 85, 2, 69, 78, 2010年02月15日
  日本語
• 人獣共通感染症としての結核
  鈴木 定彦; 松葉 隆司; 中島 千絵, 結核, 85, 2, 79, 86, 2010年02月
  (一社)日本結核病学会, 日本語
• 新規コレクチンの発見
  大谷 克城; 鈴木 定彦; 若宮 伸隆, 旭川医科大学研究フォーラム, 10, 1, 2, 12, 2010年02月
  旭川医科大学, 日本語
• ＤＮＡマイクロアレイを用いた薬剤耐性らい菌の簡易検出法の創出と、その開発途上国における有用性
  松岡正典; 鈴木定彦; 牧野正直, 日本ハンセン病学会誌, 79, 3, 257, 261, 2010年
  英語
• 南極およびオホーツク海で採取した流氷における構成菌種の同定と薬剤耐性遺伝子の検出
  登坂唯香; 中島千絵; 大久保寅彦; 石原加奈子; 鈴木定彦; 伊村智; 田村豊, 極域科学・宙空圏・気水圏・生物・地学シンポジウム講演予稿集(CD-ROM), 2010, ROMBUNNO.PB23, 2010年
  日本語
• 輸入感染症としての多剤耐性結核の対策・制御に関する研究 非結核性抗酸菌症患者の潜伏結核感染 ハルピンの薬剤耐性結核の起源
  服部俊夫; 凌虹; 鈴木定彦, 輸入感染症としての多剤耐性結核の対策・制御に関する研究 平成21年度 総括・分担研究報告書, 82, 87, 2010年
  日本語
• DNAマイクロアレイを用いた薬剤耐性らい菌の簡易検出法の創出と,その開発途上国における有用性
  松岡正典; 鈴木定彦; 牧野正直, Jpn J Lepr, 79, 3, 257, 261, 2010年
  英語
• Zoonotic aspects of tuberculosis caused by mycobacterium bovis
  Yasuhiko Suzuki; Takashi Matsuba; Chie Nakajima, Kekkaku, 85, 2, 79, 86, 2010年, ［査読有り］, ［国内誌］
  2, 日本語
• A novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries
  Masanori Matsuoka; Yasuhiko Suzuki; Masanao Makino, Japanese Journal of Leprosy, 79, 3, 257, 261, 2010年, ［査読有り］, ［国内誌］
  3, 英語
• バングラデシュにおいて猿から分離された結核菌群菌
  中島千絵; 鈴木定彦, 感染症学雑誌, 83, 5, 631, 2009年09月20日
  日本語
• バングラデシュの多剤耐性結核菌における耐性に関与する遺伝子変異
  鈴木定彦; 中島千絵; 田丸亜貴, 感染症学雑誌, 83, 5, 631, 2009年09月20日
  日本語
• スカベンジャー受容体コレクチンCL-P1のリガンド認識ドメインの解析
  森 健一郎; 大谷 克城; 張 成宰; 金 然旭; 本村 亘; 孫 啓輝; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 日本生化学会大会プログラム・講演要旨集, 82回, 4T20p, 12, 2009年09月
  (公社)日本生化学会, 日本語
• ドメイン欠損CL-P1のリガンド結合解析
  森 健一郎; 大谷 克城; 張 成宰; 金 然旭; 本村 亘; 孫 啓輝; 吉田 逸朗; 鈴木 定彦; 若宮 伸隆, 補体シンポジウム講演集, 46, 29, 30, 2009年08月
  (一社)日本補体学会, 日本語
• 人獣共通感染症としての結核
  鈴木定彦, 結核, 84, 5, 281, 2009年05月15日
  日本語
• 肺Mycobacteirum avium complex症患者由来M.aviumと豚由来M.aviumの血清型比較
  西内由紀子; 田栗貴博; 松本壮吉; 立石善隆; 北田清悟; 田丸亜貴; 鈴木定彦; 前倉亮治, 結核, 84, 5, 409, 2009年05月15日
  日本語
• MLPA法による多剤耐性結核菌の検出
  田丸亜貴; 河原隆二; 松本壮吉; 鈴木定彦, 結核, 84, 5, 397, 2009年05月15日
  日本語
• 結核と非結核性抗酸菌症診療の新展開 6.超多剤耐性結核菌における耐性化のメカニズムと耐性化防止対策
  鈴木定彦; 中島千絵; 福島由華里; 田丸亜貴; 松葉隆司, 化学療法の領域, 25, 4, 612, 620, 2009年03月25日
  日本語
• 生活環境に分布するMycobacterium avium complexと臨床分離株の多型解析
  西内由紀子; 松本壮吉; 立石善隆; 鈴木定彦, 日本細菌学雑誌, 64, 1, 96, 2009年02月20日
  日本語
• 超多剤耐性結核菌における耐性のメカニズムと耐性化防止対策
  鈴木定彦; 中島千絵; 福島由華里; 田丸亜貴; 松葉隆司, 化学療法の領域, 25, 612, 620, 2009年
• コレクチンCL‐P1のリガンド認識ドメインの解析
  森健一郎; 大谷克城; JANG SeongJae; KIM YounUck; 本村亘; SUN QiHui; 吉田逸朗; 鈴木定彦; 若宮伸隆, 日本分子生物学会年会講演要旨集, 32nd, Vol.1, 74, 2009年
  日本語
• 特徴ある感染症対策―Post‐exposure Prophylaxis:PEPを中心に 曝露後発症対策(Post‐exposure Prophylaxis:PEP)結核(化学予防)
  鈴木定彦; 中島千絵; 福島由華里; 田丸亜貴; 松葉隆司, 臨床と微生物, 35, 6, 669, 675, 2008年11月25日
  日本語
• マルチプレックスPCR法を用いたバングラデシュにおける結核菌群菌の浸淫度調査
  中島千絵; 鈴木定彦, 感染症学雑誌, 82, 6, 723, 724, 2008年11月20日
  日本語
• 人及び豚の抗酸菌感染症に由来するMycobacterium aviumの遺伝学的特長の比較
  中島千絵; 田村豊; 田丸亜貴; 鈴木定彦, 感染症学雑誌, 82, 6, 767, 2008年11月20日
  日本語
• 動物病院におけるメチシリン耐性黄色ブドウ球菌の伝播
  田村豊; 村松康和; 中島千絵; 柳沢千恵; 鈴木定彦; 花木秀明, 感染症学雑誌, 82, 6, 669, 2008年11月20日
  日本語
• 【自然免疫と生体防御レクチン】新規コレクチンCL-L1,CL-P1,CL-K1の構造と機能
  鈴木 定彦; 大谷 克城; 張 成宰; 本村 亘; 若宮 伸隆, 臨床検査, 52, 8, 861, 869, 2008年08月
  (株)医学書院, 日本語
• Streptococus mutans由来sucrose phosphorylaseの熱安定性に関する研究
  高本鉄兵; 深田はるみ; 久保亜希子; 鈴木定彦; 北村進一, J Appl Glycosci, 55, Suppl., 51, 2008年07月20日
  日本語
• 結核の化学予防
  鈴木定彦; 中島千絵; 福島由華里; 田丸亜貴; 松葉隆司, 臨床と微生物, 25, 669, 675, 2008年
• Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through CXCR4.
  Xiao P; Usami O; Suzuki Y; Ling H; Shimizu N; Hoshino H; Zhuang M; Ashino Y; Gu H; Hattori T, AIDS, 22, 1749, 1759, 2008年
• Anti-rabies antibodies in Japanese volunteers immunized with imported vaccine.
  Usuzawa m; Changa-Yasutan H; Jitthiang P; Promjunyakul W; Medina P; Demetria C; Miranda ME; Suzuki Y; Oshitani H; Hattori T, Southeast Asian Journal of Tropical Medicine and Public Health, 39, suppl 1, 68, 72, 2008年
• 【胎盤】ヒト胎盤コレクチン1
  大谷 克城; 鈴木 定彦; 若宮 伸隆, 臨床検査, 51, 13, 1714, 1718, 2007年12月
  (株)医学書院, 日本語
• 生体防御レクチンである新規コレクチンファミリーの発見とその役割
  若宮 伸隆; 大谷 克城; 坂本 隆志; 芥子 宏行; 福應 温; 張 成宰; 吉崎 隆之; 福田 光子; 小山 聡; 福澤 純; 本村 亘; 吉田 逸朗; 鈴木 定彦, 補体シンポジウム講演集, 44, 15, 16, 2007年08月
  (一社)日本補体学会, 日本語
• ホスホリラーゼによるアミロース合成機構の解析
  藪内梨世; 久保亜希子; 鈴木定彦; 鷹羽武史; 北村進一, J Appl Glycosci, 54, Suppl., 37, 2007年07月20日
  日本語
• 尾索動物ホヤのコレクチン遺伝子の検索と分子進化
  大谷克城; 安住薫; 鈴木定彦; JANG Seong‐Jae; 吉崎隆之; 森健一郎; 本村亘; 福澤純; 吉田逸朗; 若宮伸隆, 日本糖質学会年会要旨集, 27th, 73, 2007年07月10日
  日本語
• Evaluation and application of reverse transcription loop-mediated isothermal amplification for detection of noroviruses (vol 79, pg 326, 2007)
  T. Yoda; Y. Suzuki; K. Yamazaki; N. Sakon; M. Kanki; Aoyama, I; T. Tsukamoto, JOURNAL OF MEDICAL VIROLOGY, 79, 6, 863, 863, 2007年06月
  英語, その他
• rsmG変異によるストレプトマイシン耐性機構の解明および臨床分離結核菌における本変異の重要性
  岡本晋; 田丸亜貴; 中島千絵; 西村賢治; 田中幸徳; 徳山真治; 鈴木定彦; 越智幸三, 日本放線菌学会大会講演要旨集, 22nd, 45, 2007年05月31日
  日本語
• 肺Mycobacterium avium complex(MAC)症患者の家庭浴室内におけるMACの検出
  西内由紀子; 田丸亜貴; 北田清悟; 田栗貴博; 前倉亮治; 松本壮吉; 鈴木定彦, 結核, 82, 4, 439, 2007年04月15日
  日本語
• 薬剤耐性らい菌の簡易検出法の開発途上国への移転とそれによる耐性菌の伝播調査
  松岡正典; 鈴木定彦; TAN Esterlina; AYE Khin Saw, Jpn J Lepr, 76, 2, 141, 2007年04月01日
  日本語
• 抗生物質耐性菌のその獲得メカニズムを解明
  越智幸三; 岡本晋; 西村賢治; 鈴木定彦; 田丸亜貴; 中島千恵; 田中幸徳; 徳山真治, 食品試験研究成果情報, 19, 40, 41, 2007年03月31日
  日本語
• 家庭浴室のMycobacterium avium complexの検出―培養法,PCR法およびLAMP法の比較―
  西内由紀子; 松本壮吉; 鈴木定彦, 日本細菌学雑誌, 62, 1, 178, 178, 2007年02月25日
  日本語
• 尾索動物ホヤのコレクチン遺伝子群の検索と遺伝子進化について
  大谷克城; 安住薫; 鈴木定彦; JANG Seong‐Jae; 吉崎隆之; 森健一郎; 本村亘; 福澤純; 吉田逸朗; 若宮伸隆, 生化学, 4P-0018, 2007年
  日本語
• ウイルス感染と宿主応答・ウイルス側の要因 ヒトPBMC移植NOD/SCIDマウスを用いたin vivoにおけるマンノースバインディングレクチンの抗HIV活性の評価
  堀端 重男; 大谷 克城; 坂本 隆志; 岸 雄一郎; 木佐木 博; 鈴木 定彦; 駒野 淳; 山本 直樹; 若宮 伸隆; 本多 三男, 日本免疫学会総会・学術集会記録, 36, 202, 202, 2006年11月
  (NPO)日本免疫学会, 日本語
• 多剤耐性結核の現状と今後 6.多剤耐性結核の菌検出法の進歩
  鈴木定彦; 田丸亜貴; 中島千絵; 西原みづき; 福島由華里; 松葉隆司, 化学療法の領域, 22, 11, 1705, 1713, 2006年10月25日
  日本語
• M.lepraeの迅速薬剤感受性試験法
  鈴木定彦; 松岡正典, Jpn J Lepr, 75, 2, 102, 102, 2006年04月01日
  日本語
• 新規ヒト化抗すい癌ムチン抗体の作製とその基礎的解析
  木村健二郎; 沢田鉄二; 小松みどり; 六車一哉; 西原承浩; 山下好人; 八代正和; 山田靖哉; 加藤保之; 平川弘聖; 鈴木定彦, 日本外科学会雑誌, 107, 2, 563, 563, 2006年03月05日
  一般社団法人日本外科学会, 日本語
• 【TLR以外のパターン認識レセプターとその役割】コレクチンとその免疫応答における役割
  大谷 克城; 鈴木 定彦; 若宮 伸隆, 臨床免疫, 45, 3, 266, 274, 2006年03月
  (有)科学評論社, 日本語
• テトラサイクリンを用いた発現制御ベクターによる結核菌糖タンパクの発現
  松葉隆司; 鈴木定彦; 田中吉紀, 日本細菌学雑誌, 61, 1, 85, 2006年02月25日
  日本語
• コレクチンとその免疫応答における役割
  大谷克城; 鈴木定彦; 若宮伸隆, 臨床免疫, 45, 266, 274, 2006年
• 多剤耐性結核菌検出法の進歩
  鈴木定彦; 田丸亜貴; 中島千絵; 西原みづき; 福島由華里; 松葉隆司, 化学療法の領域, 22, 1705, 1713, 2006年
• 抗酸菌感染の国際的対応への貢献を目指した基盤に関する研究 結核菌の同定,耐性検査へのマイクロアレイの応用に関する研究―DNAマイクロアレイを用いた結核菌の分子疫学的解析法の構築―
  鈴木定彦, 抗酸菌感染の国際的対応への貢献を目指した基盤に関する研究 平成17年度 総括・分担研究報告書, 65, 69, 2006年
  日本語
• DNAマイクロアレイを用いたMycobacterium lepraeの迅速薬剤感受性試験法
  鈴木定彦; 松岡正典, Jpn J Lepr, 75, 3, 271, 277, 2006年, ［国内誌］
  3, 中国語
• Avian flu: Isolation of drug-resistant H5N1 virus (vol 437, pg 1108, 2005)
  QM Le; M Kiso; K Someya; YT Sakai; TH Nguyen; KHL Nguyen; ND Pham; HH Ngyen; S Yamada; Y Muramoto; T Horimoto; A Takada; H Goto; T Suzuki; Y Suzuki; Y Kawaoka, NATURE, 438, 7069, 754, 754, 2005年12月
  英語, その他
• 大気浮遊粉じん中のビスフェノールAと多環芳香族炭化水素との濃度相関
  松本比佐志; 鈴木定彦, 大阪府立公衆衛生研究所研究報告, 43, 7, 16, 2005年11月
  大阪府立公衆衛生研究所, 日本語
• Mannose binding lectinによるHIV-1複製の非特異的抑制効果
  滝澤 万里; 大谷 克城; 岸 雄一郎; 坂本 高志; 鈴木 定彦; 若宮 伸隆; 本多 三男, 日本免疫学会総会・学術集会記録, 35, 182, 182, 2005年11月
  (NPO)日本免疫学会, 日本語
• 新しいアッセイ用ほ乳類細胞(CHOOSER)を用いた簡便,高感度で再現性の良いエストロゲン様活性測定方法の開発
  足立伸一; 山本康次; 織田肇; 小野芳朗; 鈴木定彦, 水環境学会誌, 28, 7, 451, 456, 2005年07月10日
  Several in vitro assays have been developed to assess the activity of estrogenic substances. Recently, a yeast two-hybrid screen or a MCF-7 (human breast cancer cell) screen has been adopted mainly for screening chemicals and environmental estrogenic activity. However a yeast two-hybrid screen does not assay using an animal cell. MCF-7 screen is a complicated assay and the cell used proliferates depending on estrogen, thus obstructing a precise assay for estrogenic activity. In addition both screens need long incubation period (4-6 days) for a highly sensitive assay. The CHOOSER is a Chinese hamster ovary (CHO) cell transformed with the gene encoding the human estrogen receptor (ER α) and an estrogen responsive promoter linked to a reporter gene which was developed by Suzuki et. al. at Osaka prefectural institute of public health. When the reporter gene is activated by estrogenic substances, is expressed, producing alkaline phosphatase which is secreted into the medium. The CHOOSER can assay high sensitively (under 10-11M as 17 β-estradiol) at any time in a short incubation period (2 days). The number of the CHOOSER can be counted precisely because a CHO is dissociated the aggregates easily with trypsin and form a single cell suspension. And the CHOOSER can proliferate in the medium without estrogen, therefore it is possible to assay for estrogenic activity more proliferate in the medium without estrogen, therefore it is possible to assay for estrogenic activity more precisely. The CHOOSER assay will be a useful prescreening method for estrogenic activity before in vivo assay., 公益社団法人 日本水環境学会, 日本語
• 薬剤耐性らい菌の遺伝子変異およびその簡易検出法の開発
  松岡正典; 張良ふん; 鈴木定彦; 吉川陽子, Jpn J Lepr, 74, 2, 121, 121, 2005年04月01日
  日本語
• 不織布核酸精製キットを用いたLAMP法によるかくたんからの抗酸菌検出
  田丸亜貴; 小田直純; 深沢忠; 鈴木定彦; 和田恭直, 結核, 80, 3, 322, 2005年03月15日
  日本語
• 結核菌Rv0679cタンパクの局在と性状解析
  松葉隆司; 鈴木定彦; 田中吉紀, 日本細菌学雑誌, 60, 1, 132, 2005年02月25日
  日本語
• 新しい感染症検査法の発展と動向 2. 薬剤耐性結核菌のDNAマイクロアレイ検出
  鈴木定彦; 吉川陽子; 田丸亜貴; 田中吉紀, 化学療法の領域, 21, 3, 334, 342, 2005年02月25日
  日本語
• 薬剤耐性結核菌のDNAマイクロアレイ検出
  鈴木定彦; 吉川陽子; 田丸亜貴; 田中吉紀, 化学療法の領域, 21, 334, 342, 2005年
• 新規コレクチンCL-K1(Colec11)の生体内局在と分子生物学的解析
  芥子 宏行; 坂本 隆志; 大谷 克城; 鈴木 定彦; 若宮 伸隆, 日本免疫学会総会・学術集会記録, 34, 153, 153, 2004年11月
  (NPO)日本免疫学会, 日本語
• 紫外線吸収剤及びその関連化合物によるエストロゲン様作用
  松本比佐志; 足立伸一; 鈴木定彦, 日本食品化学学会総会・学術大会講演要旨集, 10th, 66, 2004年06月17日
  日本語
• 結核菌のキノロン系抗生物質に対する交差耐性とDNAジャイレース遺伝子上の変異の相関
  鈴木定彦; 松葉隆司; 斎藤肇; 田中吉紀, 日本細菌学雑誌, 59, 1, 114, 2004年02月25日
  日本語
• 臨床分離株間で一アミノ酸置換を有する結核菌タンパクに対するモノクローナル抗体作出
  松葉隆司; 鈴木定彦; 田中吉紀, 日本細菌学雑誌, 59, 1, 157, 2004年02月25日
  日本語
• 創薬のための生体機能解析に関する研究 レクチン機能を利用した血管における生体防御システムの解明と創薬への応用
  若宮伸隆; 本多三男; 鈴木定彦; 板部洋之; 岸雄一郎, 創薬等ヒューマンサイエンス研究総合研究報告書 平成13-15年度 第2分野 創薬のための生体機能解析に関する研究, 85, 89, 2004年
  日本語
• 創薬のための生体機能解析に関する研究 レクチン機能を利用した血管における生体防御システムの解明と創薬への応用
  若宮伸隆; 本多三男; 鈴木定彦; 板部洋之; 岸雄一郎, 創薬等ヒューマンサイエンス研究重点研究報告書 平成15年度 第2分野 創薬のための生体機能解析に関する研究, 67, 73, 2004年
  日本語
• 遺伝子を標的とした感染症の迅速検査法の進歩 DNAマイクロアレイを用いた臨床分離結核菌の薬剤耐性判定
  吉川陽子; 市原竜生; 鈴木定彦, JARMAM, 14, 1, 45, 50, 2003年12月25日
  日本語
• Characterization of clinical isolates of Mycobacterium tuberculosis resistant to drugs and detection of RpoB mutation in multidrug-resistant tuberculosis in the Philippines
  DMD Agdamag; S Kageyama; R Solante; AS Espantaleon; JCE Sangco; Y Suzuki, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, 7, 11, 1104, 1108, 2003年11月
  英語
• 好アルカリ菌Bacillus clausiiからの溶菌酵素遺伝子のクローニングと発現
  井川聡; 増井昭彦; 鈴木定彦; 藤原信明, 日本生物工学会大会講演要旨集, 2003, 58, 58, 2003年08月25日
  日本生物工学会, 日本語
• Cloning and expression of a UDP-glucuronic acid decarboxylase gene in rice
  K Suzuki; Y Suzuki; S Kitamura, JOURNAL OF EXPERIMENTAL BOTANY, 54, 389, 1997, 1999, 2003年08月
  英語
• コレクチンと生体防御
  鈴木定彦; 加瀬哲男, 大阪府立公衆衛生研究所ニュース, 21, 2, 3, 2003年06月06日
  日本語
• Precise characterization of norovirus (Norwalk-like virus)-specific monoclonal antibodies with broad reactivity
  T Yoda; Y Suzuki; Y Terano; K Yamazaki; N Sakon; T Kuzuguchi; H Oda; T Tsukamoto, JOURNAL OF CLINICAL MICROBIOLOGY, 41, 6, 2367, 2371, 2003年06月
  英語
• ニワトリ由来Cryptosporidium sp.の分子生物学的手法による種の同定
  木村明生; 鈴木定彦; 松井利博, 日本獣医学会学術集会講演要旨集, 135th, 91, 2003年03月25日
  日本語
• イネのUDP‐グルクロン酸デカルボキシラーゼのクローニングと発現解析
  鈴木潔; 鈴木定彦; 北村進一, 日本農芸化学会大会講演要旨集, 2003, 134, 2003年03月05日
  日本語
• CL-P1, a Newly Cloned Endothelial Cell Specific Scavenger Receptor
  Fukuzawa Jun; Osaki Junzo; Saito Tetsuya; Baljinnyam Erdene; Sakuragi Hitoshi; Yao Naoyuki; Haneda Takashi; Hasebe Naoyuki; Kikuchi Kenjiro; Itabe Hiroyuki; Takeuchi Masayoshi; Koyama Satoshi; Koge Keiichi; Ohtani Katsuki; Fukuoh Atsushi; Suzuki Yasuhiko; Wakamiya Nobutaka, Circulation journal : official journal of the Japanese Circulation Society, 67, 114, 114, 2003年03月01日
  社団法人日本循環器学会, 英語
• Haplotype analysis of the human collectin placenta 1 (hCL-P1) gene
  H Ohmori; Y Makita; M Funamizu; S Chiba; K Ohtani; Y Suzuki; N Wakamiya; A Hata, JOURNAL OF HUMAN GENETICS, 48, 2, 82, 85, 2003年
  英語
• レクチン機能を利用した血管における生体防御システムの解明と創薬への応用
  若宮伸隆; 本多三男; 鈴木定彦; 板部洋之; 岸雄一郎, 創薬等ヒューマンサイエンス研究重点研究報告書 平成14年度 第2分野 創薬のための生体機能解析に関する研究, 72, 76, 2003年
  日本語
• Molecular cloning of mouse collectin liver 1
  T Kawai; Y Suzuki; S Eda; T Kase; K Ohtani; Y Sakai; H Keshi; A Fukuoh; T Sakamoto; M Nozaki; NG Copeland; NA Jenkins; N Wakamiya, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 66, 10, 2134, 2145, 2002年10月
  英語
• Isolation of a novel mouse variant of the drs tumor suppressor gene
  T Kawai; Y Suzuki; A Yamashita; H Inoue, CANCER LETTERS, 183, 1, 79, 86, 2002年09月
  英語
• 心血管疾患と炎症 新しくクローニングされた内皮特異的スカベンジャー受容体CL-P1
  福澤 純; 小山 聡; 高下 圭一; 長谷部 直幸; 菊池 健次郎; 大谷 克城; 福應 温; 鈴木 定彦; 若宮 伸隆, Journal of Cardiology, 40, Suppl.1, 91, 91, 2002年08月
  (一社)日本心臓病学会, 日本語
• 血管内皮特異的スガベンジャー受容体CL-P1の細胞内領域結合分子の解析
  福應 温; 大谷 克城; 坂本 隆志; 芥子 宏行; 鈴木 定彦; 福澤 純; 小山 聡; 高下 圭一; 小笠原 正洋; 吉田 逸朗; 若宮 伸隆, 生化学, 74, 8, 1097, 1097, 2002年08月
  (公社)日本生化学会, 日本語
• 血管内皮に発現するスカベンジャー受容体様コレクチンCL‐P1のクローニングと機能の解析
  大谷克城; 鈴木定彦; 坂本隆志; 江田宗司; 河合高生; 福応温; 芥子宏行; 若宮伸隆, 日本糖質学会年会要旨集, 23rd, 87, 2002年07月25日
  日本語
• 新規コレクチン遺伝子群のクローニングとその分子進化について
  鈴木定彦; 大谷克城; 坂本隆志; 江田宗司; 河合高生; 福応温; 芥子宏行; 若宮伸隆, 日本糖質学会年会要旨集, 23rd, 46, 2002年07月25日
  日本語
• Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice
  T Shimada; K Inoue; Y Suzuki; T Kawai; E Azuma; T Nakajima; M Shindo; K Kurose; A Sugie; Y Yamagishi; Y Fujii-Kuriyama; M Hashimoto, CARCINOGENESIS, 23, 7, 1199, 1207, 2002年07月
  英語
• 結核菌青山B株全染色体コスミド整列クローンライブラリーの作成 IS6110と本株の特徴
  陵本功子; 中嶋一彦; 下山孝; 鈴木定彦; 田村俊秀, 結核, 77, 3, 262, 2002年03月15日
  日本語
• 大気浮遊粉じん中のビスフェノールAの検出と多環芳香族炭化水素との相関
  松本比佐志; 鈴木定彦, 日本薬学会年会要旨集, 122nd, 3, 187, 2002年03月05日
  日本語
• 熱帯熱マラリア原虫の赤血球侵入に対する動物血清レクチンの阻害効果
  大西義博; 木村明生; 鈴木定彦; 西村和彦, 日本寄生虫学会大会プログラム・抄録集, 71st, 85, 2002年03月01日
  日本語
• 蛍光抗体法スライド上でのCryptosporidium parvumオーシスト同定の試み
  木村明生; 鈴木定彦; 楠原康弘; 木俣勲; 井関基弘, 日本寄生虫学会大会プログラム・抄録集, 71st, 158, 2002年03月01日
  日本語
• Identification of human mannose binding lectin (MBL) recognition sites for novel inhibitory antibodies.
  Hui Zhao; Nobutaka Wakamiya; Yasuhiko Suzuki; Matthew T Hamonko; Gregory L Stahl, Hybridoma and hybridomics, 21, 1, 25, 36, 2002年02月, ［国際誌］
  Mannose binding lectin (MBL) binding initiates activation of the lectin complement pathway. Recent studies from our laboratory have demonstrated that MBL-dependent complement activation mediates cellular injury following oxidative stress in vivo and in vitro. A panel of novel inhibitory monoclonal antibodies (MAbs) against MBL (e.g., MAb 3F8, 2A9, and hMBL1.2) has been developed that inhibit MBL binding and lectin pathway activation. Here, we further characterized the interactions of these MAbs and their Fab fragments to MBL. Whole MAbs or their Fab fragments bound to MBL with relatively high affinity. Fab fragments of 3F8 were functionally effective in inhibiting MBL-dependent complement activation, however, steric hindrance of MAb 2A9 was essential for inhibition of MBL-dependent complement activation. We identified the hinge region, and residues EDCVLLL within the carbohydrate recognition domain of MBL as the recognition sites for MAb 3F8 and 2A9, respectively. The interaction of MAbs (e.g., 3F8 and 2A9) to MBL was dependent on the conformation of their recognition sites. These findings demonstrate that MBL binding can be inhibited by at least two separate and independent mechanisms., 英語
• Rapid detection of pyrazinamide-resistant Mycobacterium tuberculosis by a PCR-based in vitro system
  Y Suzuki; A Suzuki; A Tamaru; C Katsukawa; H Oda, JOURNAL OF CLINICAL MICROBIOLOGY, 40, 2, 501, 507, 2002年02月
  英語
• 若宮伸隆、鈴木定彦. MBLとその機能を生理学的意義
  臨床病理中四会誌, 17, 2, 12, 2002年
• Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection
  Yukiya Hakozaki; Makoto Yoshiba; Kazuhiko Sekiyama; Eiji Seike; Junichi Iwamoto; Keiji Mitani; Masafumi Mine; Toshio Morizane; Katsuki Ohtani; Yasuhiko Suzuki; Nobutaka Wakamiya, Liver, 22, 1, 29, 34, 2002年
  英語
• レクチン機能を利用した血管における生体防御システムの解明と創薬への応用
  若宮伸隆; 鈴木定彦; 板部洋之; 本多三男; 岸雄一郎, 創薬等ヒューマンサイエンス研究重点研究報告書 平成13年度 第2分野 創薬のための生体機能解析に関する研究, 74, 83, 2002年
  日本語
• 感染防御とコレクチンファミリー
  鈴木定彦; 若宮伸隆, Annual Review 免疫, 2002, 217, 225, 2002年
  中外医学社, 日本語
• MCF‐7細胞増殖を誘発する大気浮遊粉じん中のビスフェノールA
  松本比佐志; 鈴木定彦, 日本内分泌かく乱化学物質学会研究発表会要旨集, 4th, 129, 2001年12月
  日本語
• The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Keshi; Y Sakai; A Fukuoh; T Sakamoto; H Itabe; T Suzutani; M Gasawara; Yoshida, I; N Wakamiya, JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 47, 44222, 44228, 2001年11月
  英語
• 腎臓由来新規コレクチン(CL‐K1)のクローニング
  芥子宏行; 河合高生; 鈴木定彦; 大谷克城; 福応温; 若宮伸隆, 日本免疫学会総会・学術集会記録, 31, 233, 2001年10月31日
  日本語
• 新規膜型コレクチンCL‐P1のクローニングと機能解析
  大谷克城; 鈴木定彦; 坂本隆志; 芥子宏行; 福応温; 若宮伸隆, 日本免疫学会総会・学術集会記録, 31, 234, 2001年10月31日
  日本語
• Characterization of Norwalk virus GI specific monoclonal antibodies generated against Escherichia coli expressed capsid protein and the reactivity of two broadly reactive monoclonal antibodies generated against GII capsid towards GI recombinant fragments
  Tomoko Yoda; Yoshitake Terano; Yasuhiko Suzuki; Kenji Yamazaki; Isao Oishi; Tsuyoshi Kuzuguchi; Hiroyoshi Kawamoto; Etsuko Utagawa; Koichi Takino; Hajime Oda; Tadayoshi Shibata, BMC Microbiology, 1, 1, 1, 11, 2001年10月08日
  BioMed Central Ltd., 英語
• Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall
  S Tsuji; J Uehori; M Matsumoto; Y Suzuki; A Matsuhisa; K Toyoshima; T Seya, JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 26, 23456, 23463, 2001年06月
  英語
• Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome
  A Tsutsumi; K Sasaki; N Wakamiya; K Ichikawa; T Atsumi; K Ohtani; Y Suzuki; T Koike; T Sumida, GENES AND IMMUNITY, 2, 2, 99, 104, 2001年04月
  英語
• Recombinant expression of human mannan-binding lectin
  T Vorup-Jensen; ES Sorensen; UB Jensen; W Schwaeble; T Kawasaki; Y Ma; K Uemura; N Wakamiya; Y Suzuki; TG Jensen; K Takahashi; RAB Ezekowitz; S Thiel; JC Jensenius, INTERNATIONAL IMMUNOPHARMACOLOGY, 1, 4, 677, 687, 2001年04月
  英語
• 耐性菌シリーズ 4 結核菌の薬剤耐性
  鈴木定彦; 鈴木文; 田丸亜貴; 勝川千尋, 感染症, 31, 2, 77-83,75-76, 83, 2001年03月20日
  アステラス製薬(株), 日本語
• IS1245をプローブとしたMycobacterium aviumのRFLP分析
  田丸亜貴; 鈴木定彦; 阿野裕美; 吉多仁子, 結核, 76, 3, 328, 2001年03月15日
  日本語
• DNAチップ技術を用いた結核菌分子疫学的解析法の開発
  鈴木定彦; 田丸亜貴, 結核, 76, 3, 328, 2001年03月15日
  日本語
• Molecular cloning and characterization of the gene coding for azoreductase from Bacillus sp OY1-2 isolated from soil
  Y Suzuki; T Yoda; A Ruhul; W Sugiura, JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 12, 9059, 9065, 2001年03月
  英語
• 【スカベンジャー受容体ファミリーと異物排除の分子機構】新規膜型コレクチンは,血管内皮に存在し,スカベンジャー様機能をもつ
  若宮 伸隆; 鈴木 定彦, 生化学, 73, 3, 205, 208, 2001年03月
  (公社)日本生化学会, 日本語
• 微生物の薬剤耐性 細菌の化学療法剤と薬剤耐性 結核菌
  鈴木定彦; 鈴木文; 田丸亜貴; 勝川千尋, 臨床と微生物, 28, 1, 35, 41, 2001年01月25日
  日本語
• 鈴木定彦、若宮伸隆 感染防御とコレクチンファミリーAnnual Review
  免疫, 2002, 217, 225, 2001年
• 若宮伸隆、鈴木定彦 膜型コレクチンは血管内皮に存在しスカベンジャーレセプター様の機能を持つ
  生化学, 73, 205, 208, 2001年
• 鈴木定彦、田丸亜貴、鈴木文、勝川千尋 結核菌の薬剤耐性
  感染症, 31, 75, 83, 2001年
• 鈴木定彦、田丸亜貴、鈴木文、勝川千尋 結核菌の化学療法剤と薬剤耐性
  臨床と微生物, 28, 35, 41, 2001年
• Expression of glycosylated human interferon-beta in high levels in Chinese Hamster Ovary (CHO) cells
  J. Biol. Macromolec, 1, 12, 18, 2001年
• Comparison of self-ligation mediated polymerase chain reaction and mixed-linker polymerase chain reaction in molecular epidemiology of tuberculosis
  Kekkaku, 76, 9, 18, 2001年
• ハンセン氏病における動物血清レクチンの感染防止効果について (ヒューマンサイエンス振興財団S)
  若宮伸隆; WISNU I M; 岸雄一郎; 本多三男; 鈴木定彦, 創薬等ヒューマンサイエンス研究 平成12年度 国際共同研究事業研究報告書, 78, 85, 2001年
  日本語
• DNAマイクロアレイを使った結核菌薬剤耐性遺伝子の迅速検出
  市原竜生; 鈴木定彦, 日本臨床微生物学雑誌, 10, 4, 93, 95, 2000年12月25日
  日本臨床微生物学会, 日本語
• 結核 分子遺伝学からのアプローチ
  長谷川好規; 阿部千代治; 飯沼由嗣; 鈴木定彦; 高橋光良; 水口康雄, 結核, 75, 12, 725, 728, 2000年12月15日
  Recent progress of molecular genetics has been providing tools for new approaches to disease treatment and diagnosis of Mycobacterium tuberculosis. In 1998, Cole et al. reported the complete genome sequence of Mycobacterium tuberculosis. The new informa tion will provide us the knowledge and understanding of the biology of Mycobacterium tuberculosis. Further, it will provide us new conception of diagnosis and treatment of the disease. Four topics were selected in this symposium. Dr. Iinuma reviewed and prospected the clinical utility of nucleic acid amplification methods of Mycobacterium tuberculosis. Dr. Suzuki reviewed the molecular mechanism of acquired resistance to anti-TB drugs and reported the early detection of genetic mutation by new designed DNA tip method. Dr. Takahashi reviewed the method of molecular epidemiology and genetic elements as a tool for strain differentiation of tuberculosis. Dr. Mizuguchi interpreted the essential feature of mycobacterial genome maps, and genes and their biological activity. He also reviewed the importance and the utility of the complete genome sequence of tuberculosis in asso ciation with pathogenecity. These topics were summarized in this report, based on the symposium of "Molecular genetic approaches to Mycobacterium tuberculosis " in the 75 thannual meeting of the Japanese Society for Tuberculosis., JAPANESE SOCIETY FOR TUBERCULOSIS, 日本語
• 膜型コレクチンCL‐P1は血管内皮に発現し,スカベンジャーレセプター様の機能を示す
  大谷克城; 鈴木定彦; 坂本隆志; 芥子宏行; 福応温; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 311, 2000年11月25日
  日本語
• 結核の現状と課題 結核菌の薬剤耐性と関与遺伝子
  鈴木定彦; 鈴木文; 田丸亜貴; 勝川千尋, Pharma Med, 18, 10, 47, 53, 2000年10月10日
  (株)メディカルレビュー社, 日本語
• Recognition of N-glycolylneuraminic acid linked to galactose by the alpha 2,3 linkage is associated with intestinal replication of influenza A virus in ducks
  T Ito; Y Suzuki; T Suzuki; A Takada; T Horimoto; K Wells; H Kida; K Otsuki; M Kiso; H Ishida; Y Kawaoka, JOURNAL OF VIROLOGY, 74, 19, 9300, 9305, 2000年10月
  英語
• 結核菌の薬剤耐性獲得機序の解析と迅速診断への展開
  鈴木定彦; 田丸亜貴; RUHUL A; 勝川千尋, 防菌防ばい, 28, 9, 561, 573, 2000年09月10日
  日本防菌防黴学会, 日本語
• Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection
  K Sasaki; A Tsutsumi; N Wakamiya; K Ohtani; Y Suzuki; Y Watanabe; N Nakayama; T Koike, SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 35, 9, 960, 965, 2000年09月
  英語
• 日本人におけるMBL(mannan-binding lectin)遺伝子変異と血中濃度の検討
  芥子 宏行; 大谷 克城; 坂本 隆志; 岸 雄一郎; 荒木 宏昌; 鈴木 定彦; 若宮 伸隆, 医学のあゆみ, 194, 12, 957, 958, 2000年09月
  健常日本人497例におけるMBL遺伝子変異と血中濃度の測定により,MBLの遺伝子多型はコドン54のみにみられ,その頻度は野生型70.8%,ヘテロ変異型22.5%,ホモ変異型6.7%であった.本ホモ変異型の比率は欧米の比率に比べて高値であるが,血中濃度とgenotypeが十分相関しており,今後,MBLの関与が考えられる各種疾患群との比較において日本人のMBL遺伝子多型と血中濃度の一つのスタンダードになりうる, 医歯薬出版(株), 日本語
• 薬剤耐性結核菌の分子遺伝学的解析とその応用
  鈴木定彦, 薬剤耐性菌シンポジウム講演記録, 29th, 24, 27, 2000年08月24日
  日本語
• DNAチップによる結核菌の耐性診断
  鈴木定彦; 市原竜生; 田丸亜貴; RUHUL A; 勝川千尋; 牧野正直; 阿部千代治, Bio Ind, 17, 5, 36, 44, 2000年05月12日
  シ-エムシ-, 日本語
• Expression of recombinant Norwalk-like virus capsid proteins using a bacterial system and the development of its immunologic detection
  T Yoda; Y Terano; A Shimada; Y Suzuki; K Yamazaki; N Sakon; Oishi, I; ET Utagawa; Y Okuno; T Shibata, JOURNAL OF MEDICAL VIROLOGY, 60, 4, 475, 481, 2000年04月
  英語
• 【自然免疫を担う生体防御レクチン】生体防御レクチンとしてのコレクチンファミリー
  若宮 伸隆; 鈴木 定彦, 蛋白質・核酸・酵素, 45, 5, 655, 663, 2000年04月
  共立出版(株), 日本語
• 大阪府における病院内結核患者同時発生事例のRFLP解析
  田丸亜貴; 鈴木定彦, 結核, 75, 3, 292, 2000年03月15日
  日本語
• 結核菌の薬剤耐性に関与する遺伝子の解析と迅速診断への応用
  鈴木定彦, 結核, 75, 3, 225, 225, 2000年03月15日
  日本語
• 結核菌青山B株整列クローンライブラリーの作成
  陵本功子; 鈴木定彦; 下山孝; 田村俊秀, 結核, 75, 3, 329, 2000年03月15日
  日本語
• A comparative analysis of the antigenic, structural, and functional properties of three different preparations of recombinant human interleukin-18
  S Kikkawa; K Shida; H Okamura; NA Begum; M Matsumoto; S Tsuji; M Nomura; Y Suzuki; K Toyoshima; T Seya, JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 20, 2, 179, 185, 2000年02月
  英語
• 薬剤耐性結核菌の迅速診断法 DNAチップの開発
  鈴木定彦, 大阪府立公衆衛生研究所ニュース, 9, 2, 2000年01月31日
  日本語
• 結核菌の耐性診断の項目
  鈴木定彦; 市原竜生; 田丸亜貴; Amin Ruhul; 勝川千尋; 牧野正直; 阿部千代治, DNAチップ応用技術, 2000年
• 鈴木定彦、田丸亜貴、鈴木文、勝川千尋 毛核菌の薬剤耐性と関与遺伝子
  ファルマメディカ, 18, 10, 47, 53, 2000年
• 鈴木定彦、位置は癩、田丸亜貴、Amin Ruhul、勝川千尋、牧野正直、阿部千代治 DNAチップによる結核菌の耐性診断
  Bioindustry, 17, 5, 36, 44, 2000年
• 鈴木定彦、田丸亜貴、Amin Ruhul、勝川千尋 結核菌の薬剤耐性獲得機序の解析と迅速診断への展開
  防菌防黴, 28, 561, 573, 2000年
• 鈴木定彦 中高齢者の健康実態調査報告その4、コレクチンの生体防御における役割と年齢による推移
  鈴木 定彦, エストレーラ, 79, 31, 35, 2000年
  統計情報研究開発センタ-, 日本語
• 鈴木定彦、勝川千尋 結核と非定型抗酸菌症
  まこと, 110, 2000年
• 若宮伸隆、鈴木定彦 生体防御レクチンとしてのコレクチンファミリー
  蛋白質・核酸・酵素, 45, 655, 663, 2000年
• 芥子宏行、大谷克城、坂本隆志、岸雄一郎、荒木宏昌、鈴木定彦、若宮伸隆 日本人におけるMBL（mannan-binding lectin）遺伝子変異と血中濃度
  医学のあゆみ, 194, 957, 8, 2000年
• Characterization of monoclonal antibodies generated against Norwalk virus GII capsid protein expressed in Escherichia coli
  T Yoda; Y Terano; Y Suzuki; K Yamazaki; Oishi, I; E Utagawa; A Shimada; S Matsuura; M Nakajima; T Shibata, MICROBIOLOGY AND IMMUNOLOGY, 44, 11, 905, 914, 2000年
  英語
• ハンセン氏病における動物血清レクチンの感染防止効果について (ヒューマンサイエンス振興財団S)
  若宮伸隆; WISNU I M; 岸雄一郎; 本多三男; 鈴木定彦, 創薬等ヒューマンサイエンス総合研究推進事業国際共同研究報告 平成11年度, 57, 64, 2000年
  日本語
• DNAチップを用いた薬剤耐性結核菌迅速検出法の開発 (厚生省S)
  鈴木定彦, 薬剤耐性結核のサーベイランス,耐性の分子機構および多剤耐性結核の治療に関する研究 平成11年度 厚生科学研究費補助金(新興・再興感染症研究事業)研究報告書, 33, 41, 2000年
  日本語
• Substitution of amino acid residue in influenza A virus hemagglutinin affects recognition of sialyl-oligosaccharides containing N-glycolylneuraminic acid
  H Masuda; T Suzuki; Y Sugiyama; G Horiike; K Murakami; D Miyamoto; KIPJ Hidari; T Ito; H Kida; M Kiso; K Fukunaga; M Ohuchi; T Toyoda; A Ishihama; Y Kawaoka; Y Suzuki, FEBS LETTERS, 464, 1-2, 71, 74, 1999年12月
  英語
• ヒト胎盤由来新規コレクチンCL‐P1遺伝子のクローニング
  大谷克城; 鈴木定彦; 江田宗司; 河合高生; 加瀬哲男; 坂本隆志; 芥子宏行; 酒井善典; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 22nd, 306, 1999年11月22日
  日本語
• The 3 '-UT of the ubiquitous mRNA of human CD46 confers selective suppression of protein production in murine cells
  K Shida; M Nomura; M Matsumoto; Y Suzuki; K Toyoshima; T Seya, EUROPEAN JOURNAL OF IMMUNOLOGY, 29, 11, 3603, 3608, 1999年11月
  英語
• MBPのGenotype・血中濃度と慢性C型肝炎の感受性との関連性
  芥子 宏行; 大谷 克城; 箱崎 幸也; 白濱 龍興; 坂本 隆志; 鈴木 定彦; 若宮 伸隆, 日本免疫学会総会・学術集会記録, 29, 109, 109, 1999年10月
  (NPO)日本免疫学会, 日本語
• 自然免疫と獲得免疫の接点 アビディティー,アフィニティーの利用方法 コレクチンとウイルス感染
  若宮 伸隆; 大谷 克城; 加瀬 哲男; 江田 宗司; 河合 高生; 坂本 隆志; 芥子 宏行; 酒井 善典; 福應 温; 鈴木 定彦, 生化学, 71, 8, 604, 604, 1999年08月
  (公社)日本生化学会, 日本語
• Human mannan-binding lectin inhibits the infection of influenza A virus without complement
  T Kase; Y Suzuki; T Kawai; T Sakamoto; K Ohtani; S Eda; A Maeda; Y Okuno; T Kurimura; N Wakamiya, IMMUNOLOGY, 97, 3, 385, 392, 1999年07月
  英語
• Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines
  M Kurita; M Matsumoto; S Tsuji; M Kawakami; Y Suzuki; H Hayashi; K Toyoshima; T Seya, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 116, 3, 547, 553, 1999年06月
  英語
• 健常人におけるMBP(mannan-binding protein)の血中濃度とgenotype
  芥子 宏行; 大谷 克城; 坂本 隆志; 江田 宗司; 加瀬 哲男; 河合 高生; 酒井 善典; 福應 温; 鈴木 定彦; 若宮 伸隆, 補体シンポジウム講演集, 36, 83, 84, 1999年06月
  (一社)日本補体学会, 日本語
• Molecular cloning of a novel human collectin from liver (CL-L1)
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Yamazaki; T Shimada; H Keshi; Y Sakai; A Fukuoh; T Sakamoto; N Wakamiya, JOURNAL OF BIOLOGICAL CHEMISTRY, 274, 19, 13681, 13689, 1999年05月
  英語
• 田丸亜貴、鈴木定彦 RFLP分析による結核小規模感染事例の疫学的研究
  田丸 亜貴; 鈴木 定彦, 結核, 74, 74-555-561, 555, 561, 1999年
  Restriction fragment length polymorphism (RFLP) analysis was performed with 13 events considered as microepidemics of tuberculosis occurred in Osaka prefecture from July 1995 to July 1998. In 7 out of 13 events, isolates from patients involved in each event showed identical RFLP patterns, hence these events were verified as microepidemics. Out of 7 microepidemics, three were intrafamily infection, the other three occurred in work places and the remaining one was in a school occurred among students. The total number of patients who were involved in microepidemics was 19 and their ages distributed in the wide range from 18 to 69 years old, but 11 were at twenties or forties. The total delay in case-finding was 2 months in the shortest case, and more than 14 months in the longest. In the remaining 6 of 13 events, the isolates from patients were showed different RFLP patterns, although they were suspected as microepidemics. Furthermore, in the 2 microepidemics, one isolate showed different RFLP pattern from the other isolates involved in each events. These facts suggest that there could be many overlooked sources of tuberculosis infection in Osaka., JAPANESE SOCIETY FOR TUBERCULOSIS, 日本語
• High-level and effective production of human mannan-binding lectin (MBL) in Chinese hamster ovary (CHO) cells
  K Ohtani; Y Suzuki; S Eda; T Kawai; T Kase; H Keshi; Y Sakai; S Yamamoto; T Sakamoto; N Wakamiya, JOURNAL OF IMMUNOLOGICAL METHODS, 222, 1-2, 135, 144, 1999年01月
  英語
• ヒト肝臓細胞質に存在する新規コレクチンCL‐L1の遺伝子クローニング
  大谷克城; 鈴木定彦; 江田宗司; 河合高生; 加瀬哲男; 坂本隆志; 芥子宏行; 酒井善典; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 21st, 298, 1998年11月
  日本語
• 感染症学最先端 検査 結核菌の薬剤耐性検査 薬剤耐性に関与する遺伝子と迅速診断への応用の可能性
  鈴木定彦; 田丸亜貴; RUHUL A; 勝川千尋, 臨床と微生物, 25, 6, 795, 801, 1998年11月
  日本語
• 動物血清中のマンナン結合蛋白(MBP)はin vivoにおけるインフルエンザウイルス増殖に関与する
  加瀬 哲男; 大谷 克城; 江田 宗司; 河合 高生; 鈴木 定彦; 前田 章子; 奥野 良信; 坂本 隆志; 若宮 伸隆, 日本臨床免疫学会会誌, 26回抄録集, 184, 184, 1998年10月
  日本臨床免疫学会, 日本語
• 動物血清中のマンナン結合蛋白(MBP)はin vivoにおけるインフルエンザウイルス増殖に関与する
  加瀬哲男; 大谷克城; 江田宗司; 河合高生; 鈴木定彦; 前田章子; 奥野良信; 坂本隆志; 若宮伸隆, 日本免疫学会総会・学術集会記録, 28, 184, 1998年10月
  日本語
• Changes in H3 influenza A virus receptor specificity during replication in humans
  K Ryan-Poirier; Y Suzuki; WJ Bean; D Kobasa; A Takada; T Ito; Y Kawaoka, VIRUS RESEARCH, 56, 2, 169, 176, 1998年08月
  英語
• 3R(複製・修復・組換え) ヒト肝臓由来新規コレクチンCL-L1の生化学的検討
  大谷 克城; 鈴木 定彦; 江田 宗司; 河合 高生; 加瀬 哲男; 坂本 隆志; 若宮 伸隆, 生化学, 70, 8, 727, 727, 1998年08月
  (公社)日本生化学会, 日本語
• 3R(複製・修復・組換え) ヒト胎盤由来新規コレクチンCL-P1遺伝子のクローニング
  江田 宗司; 鈴木 定彦; 大谷 克城; 河合 高生; 加瀬 哲男; 坂本 隆志; 若宮 伸隆, 生化学, 70, 8, 727, 727, 1998年08月
  (公社)日本生化学会, 日本語
• Characterization of truncated human mannan-binding protein (MBP) expressed in Escherichia coli
  S Eda; Y Suzuki; T Kawai; K Ohtani; T Kase; T Sakamoto; N Wakamiya, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 62, 7, 1326, 1331, 1998年07月
  英語
• Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of Warfarin, flurbiprofen, and diclofenac by human liver microsomes
  H Yamazaki; K Inoue; K Chiba; N Ozawa; T Kawai; Y Suzuki; JA Goldstein; FP Guengerich; T Shimada, BIOCHEMICAL PHARMACOLOGY, 56, 2, 243, 251, 1998年07月
  英語
• コレクチンの感染防御における役割
  鈴木定彦, 補体シンポジウム講演集, 35th, 7, 8, 1998年07月
  日本語
• Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene
  Y Suzuki; C Katsukawa; A Tamaru; C Abe; M Makino; Y Mizuguchi; H Taniguchi, JOURNAL OF CLINICAL MICROBIOLOGY, 36, 5, 1220, 1225, 1998年05月
  英語
• Post-translational modification and intracellular localization of a splice product of CD46 cloned from human testis: role of the intracellular domains in O-glycosylation
  T Hara; Y Suzuki; T Nakazawa; H Nishimura; S Nagasawa; M Nishiguchi; M Matsumoto; M Hatanaka; M Kitamura; T Seya, IMMUNOLOGY, 93, 4, 546, 555, 1998年04月
  英語
• Molecular and biological characterization of rabbit mannan-binding protein (MBP)
  T Kawai; Y Suzuki; S Eda; K Ohtani; T Kase; T Sakamoto; H Uemura; N Wakamiya, GLYCOBIOLOGY, 8, 3, 237, 244, 1998年03月
  英語
• 大腸菌中で発現させたリコンビナント85複合体の免疫学的活性
  鈴木定彦; 勝川千尋; 田丸亜貴; 牧野正直; 松岡正典, Jpn J Lepr, 67, 1, 64, 64, 1998年03月
  日本ハンセン病学会, 日本語
• 鈴木定彦、田丸亜貴、Amin Ruhul、勝川千尋 結核菌の薬剤耐性検査；薬剤戴せ員に関与する遺伝子と迅速診断への応用の可能性
  鈴木 定彦; 田丸 亜貴; RUHUL Amin; 勝川 千尋, 臨床と微生物, 25, 25, 795, 801, 1998年
  日本語
• Regulation of promoter and intron enhancer activity in immunoglobulin heavy chain genes through late stage of B cell development
  Microbiol . Immunol, 42, 399, 405, 1998年
• Characterization of the rpsL and rrs genes of streptomycin-resistant clinical isolates of Mycobacterium tuberculosis in Japan
  E Katsukawa; A Tamaru; Y Miyata; C Abe; M Makino; Y Suzuki, JOURNAL OF APPLIED MICROBIOLOGY, 83, 5, 634, 640, 1997年11月
  英語
• 真核細胞でのヒトマンナン結合蛋白の大量発現とその生物学的性質
  大谷克城; 鈴木定彦; 江田宗司; 河合高生; 加瀬哲男; 坂本隆志; 植村英俊; 若宮伸隆, 日本免疫学会総会・学術集会記録, 27, 182, 1997年10月
  日本語
• Characterization of recombinant bovine conglutinin expressed in a mammalian cell
  Y Suzuki; S Eda; T Kawai; K Ohtani; T Kase; T Sakamoto; N Wakamiya, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 238, 3, 856, 860, 1997年09月
  英語
• Sialyl-linkage mediated selection for the appearance of host cell variants of influenza A viruses
  Y Suzuki; T Ito; H Masuda; A Takada; A Kawamoto; K Otsuki; D Miyamoto; T Suzuki; H Kida; Y Kawaoka, FASEB JOURNAL, 11, 9, A1443, A1443, 1997年07月
  英語, 研究発表ペーパー・要旨（国際会議）
• Complete nucleotide sequence of the chloroplast genome from the green alga Chlorella vulgaris: The existence of genes possibly involved in chloroplast division
  T Wakasugi; T Nagai; M Kapoor; M Sugita; M Ito; S Ito; J Tsudzuki; K Nakashima; T Tsudzuki; Y Suzuki; A Hamada; T Ohta; A Inamura; K Yoshinaga; M Sugiura, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94, 11, 5967, 5972, 1997年05月
  英語
• レクチンによるウイルス感染防御
  若宮伸隆; 鈴木定彦, 臨床免疫, 29, 4, 508, 513, 1997年04月
  日本語
• Molecular cloning and sequence analysis of the cDNA for the mouse counterpart to adult hamster liver purified growth inhibitory factor
  C Hashimoto; H Masuda; M Ayaki; Y Suzuki; A Uenaka; T Seya; J Miyoshi; K Takahashi; Y Inui, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1355, 3, 205, 208, 1997年03月
  英語
• リコンビナントM.leprae85複合体蛋白質に対する血清反応:発現系の改良によるバックグラウンド改善の試み
  鈴木定彦; 勝川千尋; 牧野正直, Jpn J Lepr, 66, 1, 41, 41, 1997年03月
  日本語
• Cloning and characterization of a cDNA encoding bovine mannan-binding protein
  T Kawai; Y Suzuki; S Eda; K Ohtani; T Kase; Y Fujinaga; T Sakamoto; T Kurimura; N Wakamiya, GENE, 186, 2, 161, 165, 1997年02月
  英語
• 若宮伸隆、鈴木定彦 レクチンによるウイルス感染制御
  臨床免疫, 29, 508, 513, 1997年
• Recombinant human surfactant protein D, lacking the N-terminal and collagenouse domains, has less bacterial agglutinating activity but is able to inhibit haemagglutination by influenze A virus
  Biochem. J., 323, 393, 399, 1997年
• Structure of a truncated human surfactant protein D is less effective in agglutinating bacteria than the native structure and fails to inhibit haemagglutination by influenza A virus.
  Eda S; Suzuki Y; Kawai T; Ohtani K; Kase T; Fujinaga Y; Sakamoto T; Kurimura T; Wakamiya N, Biochem J, 323, 2, 393, 9, 1997年
• 動物血清レクチンのインフルエンザウイルス感染阻害とその意義
  加瀬哲男; 鈴木定彦; 江田宗司; 河合高生; 大谷克城; 坂本隆志; 栗村敬; 若宮伸隆, 日本免疫学会総会・学術集会記録, 26, 427, 1996年10月
  日本語
• ウサギMBPのcDNAクローニングとその生物学的性質
  河合高生; 鈴木定彦; 江田宗司; 加瀬哲男; 大谷克城; 坂本隆志; 栗村敬; 若宮伸隆, 日本免疫学会総会・学術集会記録, 26, 266, 1996年10月
  日本語
• リコンビナントウシコングルチニンのCHO細胞での大量発現
  鈴木定彦; 江田宗司; 河合高生; 加瀬哲男; 大谷克城; 坂本隆志; 栗村敬; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 19th, 390, 1996年07月
  日本語
• ウサギMBPの精製とcDNAクローニング
  河合高生; 鈴木定彦; 江田宗司; 加瀬哲男; 大谷克城; 坂本隆志; 植村英俊; 栗村敬; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 19th, 390, 1996年07月
  日本語
• ウシMBPの精製とcDNAクローニング
  大谷克城; 鈴木定彦; 河合高生; 江田宗司; 加瀬哲男; 坂本隆志; 植村英俊; 栗村敬; 若宮伸隆, 日本分子生物学会年会プログラム・講演要旨集, 19th, 391, 1996年07月
  日本語
• Recombinant bovine conglutinin, lacking the N-terminal and collagenous domains, has less conglutination activity but is able to inhibit haemagglutination by influenza A virus
  S Eda; Y Suzuki; T Kase; T Kawai; K Ohtani; T Sakamoto; T Kurimura; N Wakamiya, BIOCHEMICAL JOURNAL, 316, 316, 43, 48, 1996年05月
  英語
• らい菌分子生物学の進展と免疫学への展開
  鈴木 定彦, 日本らい学会雑誌 = Japanese journal of leprosy, 65, 1, 37, 37, 1996年03月15日
  日本語
• らい菌MPT51類似蛋白質の大腸菌での大量発現系の構築
  鈴木 定彦; 尹 躍平; 勝川 千尋; 牧野 正直, 日本らい学会雑誌 = Japanese journal of leprosy, 65, 1, 72, 72, 1996年03月15日
  日本語
• 牧野正直、鈴木定彦 新内科学 ハンセン病の項目
  南江堂, 1996年
• 大気中の人工粒子の健康影響の防御に関する研究 (大同生命厚生事業団S)
  鈴木定彦, 第1回地域保健福祉研究助成サラリーマン(ウーマン)第3回ボランティア活動助成報告集 平成6年度, 267, 271, 1996年
  日本語
• High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation
  T Hara; Y Suzuki; T Semba; M Hatanaka; M Matsumoto; T Seya, SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 42, 6, 581, 590, 1995年12月
  英語
• 抗原刺激による免疫グロブリンH鎖イントロンエンハンサーの抑制
  東隆親; 内藤暁宏; 鈴木定彦; 多田豊ひろ, 日本免疫学会総会・学術集会記録, 25, 143, 1995年10月
  日本語
• リコンビナント動物血清レクチンの作成とそのウイルス感染初期防禦における役割
  若宮伸隆; 坂本隆志; 栗村敬; 江田宗二; 河合高生; 加瀬哲男; 大谷克城; 鈴木定彦, 日本免疫学会総会・学術集会記録, 25, 113, 1995年10月
  日本語
• らい菌MPT51類似蛋白質 (42Kd) 遺伝子のクローニング及び大腸菌中での発現
  尹 躍平; 牧野 正直; 勝川 千尋; 鈴木 定彦, 日本らい学会雑誌 = Japanese journal of leprosy, 64, 1, 63, 63, 1995年03月01日
  日本語
• らい菌85複合体Cの大腸菌中での発現
  牧野 正直; 尹 躍平; 勝川 千尋; 鈴木 定彦, 日本らい学会雑誌 = Japanese journal of leprosy, 64, 1, 64, 64, 1995年03月01日
  日本語
• Mutations in rpoB gene of rifampicin resistant clinical isolates of Mycobacterium tuberculosis in Japan
  J. Jpn. Assoc. Infect. Dis., 69, 413, 41, 1995年
• らい菌85複合体蛋白質のらい血清診断への応用 (日米医学協力研究会S)
  鈴木定彦; 勝川千尋; 田丸亜希; 牧野正直, 日米医学協力計画報告書 平成7年度, 17, 23, 1995年
  日本語
• 超可変領域に存在する“保存された”アミノ酸残基の役割
  東隆親; 木下健; 鈴木定彦, 日本免疫学会総会・学術集会記録, 24, 182, 1994年10月
  日本語
• FLUORESCENCE IN-SITU HYBRIDIZATION ANALYSIS OF CHROMOSOMAL LOCALIZATION OF 3 HUMAN CYTOCHROME-P450-2C GENES (CYP2C8, 2C9, AND 2C10) AT 10Q24.1
  K INOUE; J INAZAWA; Y SUZUKI; T SHIMADA; H YAMAZAKI; FP GUENGERICH; T ABE, JAPANESE JOURNAL OF HUMAN GENETICS, 39, 3, 337, 343, 1994年09月
  英語
• COMPARISON OF SOMATIC MUTATION FREQUENCY AMONG IMMUNOGLOBULIN GENES
  N MOTOYAMA; T MIWA; Y SUZUKI; H OKADA; T AZUMA, JOURNAL OF EXPERIMENTAL MEDICINE, 179, 2, 395, 403, 1994年02月
  英語
• インフルエンザウイルスインヒビターであるウシ・コングルチニンcDNAのクローニング
  若宮伸隆; 鈴木定彦; い躍平; 牧野正直; 栗村敬, 日本免疫学会総会・学術集会記録, 23, 292, 1993年10月
  日本語
• 体細胞突然変異発現におけるプロモーター領域の役割
  三輪隆史; 本山昇; 鈴木定彦; 岡田秀親; 東隆親, 日本免疫学会総会・学術集会記録, 23, 640, 1993年10月
  日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 その3 高製氷率運転時の熱的性能
  八十田茂; 田中俊六; 鈴木定彦; 加藤誠, 空気調和・衛生工学会学術講演会講演論文集, 1993, Pt 1, 421, 424, 1993年09月
  社団法人空気調和・衛生工学会, 日本語
• 氷蓄熱利用空調システムに関する研究 (その15) 作業時における低湿度空調空間の体感評価
  鈴木定彦; 田中俊六; 八十田茂, 日本建築学会学術講演梗概集D 環境工学, 1993, 1643, 1644, 1993年07月
  日本語
• CLONING AND SEQUENCING OF A CDNA CODING FOR BOVINE CONGLUTININ
  Y SUZUKI; YP YIN; M MAKINO; T KURIMURA; N WAKAMIYA, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 191, 2, 335, 342, 1993年03月
  英語
• 鈴木定彦 免疫学辞典 8項目担当（奥田研爾 他編）
  東京化学同人, 初版, 1993年
• Molecular Cloning and Characterization of an r RNA Operon in Streptomyces lividans TK21
  J. Bacteriol, 170, 1631, 1636, 1993年
• 氷蓄熱利用空調システムに関する研究 (その14) 空気熱交換型小容量氷蓄熱槽に関する実験研究
  鈴木定彦; 田中俊六; 八十田茂; 谷内昭仁, 日本建築学会学術講演梗概集D 環境工学, 1992, 1633, 1634, 1992年08月
  一般社団法人日本建築学会, 日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 (その3) 高製氷率運転による冷房実験結果
  八十田茂; 田中俊六; 鈴木定彦, 日本建築学会学術講演梗概集D 環境工学, 1992, 1635, 1636, 1992年08月
  一般社団法人日本建築学会, 日本語
• 氷蓄熱利用空調システムに関する研究 (その13) 住宅用氷蓄熱式空調システムの検討と小容量氷蓄熱槽の試作実験
  谷内昭仁; 田中俊六; 鈴木定彦; 八十田茂, 日本建築学会学術講演梗概集D 環境工学, 1992, 1631, 1632, 1992年08月
  一般社団法人日本建築学会, 日本語
• らい菌の細菌学(遺伝子工学)
  牧野正直; 鈴木定彦, Jpn J Lepr, 61, 2, 73, 87, 1992年07月
  日本語
• INDUCIBILITY OF PROTEIN-REACTIVE ANTIBODIES BY PEPTIDE IMMUNIZATION - COMPARISON OF 3 EPITOPE PEPTIDES OF HEN EGG-WHITE LYSOZYME
  J SEKI; XH WANG; A OTA; Y SUZUKI; N SAKATO; H FUJIO, JOURNAL OF BIOCHEMISTRY, 111, 2, 259, 264, 1992年02月
  英語
• 牧野正直、鈴木定彦 癩菌の細菌学
  M. Makino; Y. Suzuki, Jpn. J. Leprosy, 61, 2, 73, 87, 1992年
  日本語, 書評論文,書評,文献紹介等
• 氷蓄熱利用空調システムに関する研究 (その12) 低湿度高温度空調空間の体感評価
  鈴木定彦; 田中俊六; 八十田茂; 谷内昭仁, 日本建築学会学術講演梗概集D 環境工学, 1991, 1069, 1070, 1991年09月
  日本語
• ANALYSIS OF THE PROMOTER REGION IN THE RIBOSOMAL-RNA OPERON FROM MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; A NAGATA; T YAMADA, ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY, 60, 1, 7, 11, 1991年07月
  英語
• Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins
  A. Nagata; Y. Suzuki; M. Igarashi; N. Eguchi; H. Toh; Y. Urade; O. Hayaishi, Proceedings of the National Academy of Sciences of the United States of America, 88, 9, 4020, 4024, 1991年
  英語
• BCG菌のリボソームRNAオペロンのプロモーターの構造と活性
  鈴木定彦; 山田毅, 日本細菌学雑誌, 46, 1, 113, 1991年01月
  日本語
• アンチセンスコンストラクト導入によるマウスT細胞機能分子発現抑制系の開発
  鈴木定彦; 依田知子; 王暁輝; 大田明生; 藤尾啓; 坂戸信夫, 日本細菌学雑誌, 46, 1, 158, 1991年01月
  日本語
• 抗蛋白質抗体のエピトープマッピング
  大田明生; 王暁輝; 鈴木定彦; 依田知子; 坂戸信夫; 藤尾啓, 日本細菌学雑誌, 46, 1, 155, 1991年01月
  日本語
• 抗ペプチド抗体の蛋白質抗原反応性評価の問題点
  王暁輝; 大田明生; 鈴木定彦; 依田知子; 坂戸信夫; 藤尾啓, 日本細菌学雑誌, 46, 1, 156, 1991年01月
  日本語
• T細胞によるV_Lイディオタイプの認識
  坂戸信夫; 鈴木定彦; 依田知子; 大田明生; 王暁輝; 藤尾啓, 日本細菌学雑誌, 46, 1, 157, 1991年01月
  日本語
• ACTIVATION OF IDIOTYPE-SPECIFIC CD4+ T-CELL LINE - CELLULAR PROCESSING OF EXOGENOUS SELF-IMMUNOGLOBULIN
  N SAKATO; P RUGDECH; T YODA; A OTA; Y ZHAO; M SEMMA; Y SUZUKI; H FUJIO, IMMUNOLOGY, 71, 2, 153, 157, 1990年10月
  英語
• アンチセンスRNAによるマウスT細胞のCD4分子の発現抑制
  鈴木定彦; 依田知子; WANG X; 大田明生; 藤尾啓; 坂戸信夫, 日本免疫学会総会・学術集会記録, 20, 150, 1990年10月
  日本語
• ペプチド免疫による蛋白質交差反応性抗体誘導の条件
  関二郎; WANG S; 大田明生; 鈴木定彦; 依田知子; 坂戸信夫, 日本免疫学会総会・学術集会記録, 20, 153, 1990年10月
  日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 (その1) 氷蓄熱槽の概要と熱的性能確認実験結果
  田中俊六; 鈴木定彦; 八十田茂; 深谷俊英, 空気調和・衛生工学会学術講演会講演論文集, 1990, 621, 624, 1990年09月
  日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 (その2) 東海大学湘南校舎H棟における冷房実験結果
  深谷俊英; 田中俊六; 鈴木定彦; 八十田茂, 日本建築学会学術講演梗概集D 環境工学, 1990, 1159, 1160, 1990年09月
  一般社団法人日本建築学会, 日本語
• 氷蓄熱利用空調システムに関する研究 (その11) 低湿度高温度空調空間の体感評価
  鈴木定彦; 田中俊六; 八十田茂; 野村知宏, 日本建築学会学術講演梗概集D 環境工学, 1990, 1161, 1162, 1990年09月
  一般社団法人日本建築学会, 日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 (その2) 東海大学湘南校舎H棟における冷暖房実験結果
  田中俊六; 鈴木定彦; 八十田茂; 深谷俊英, 空気調和・衛生工学会学術講演会講演論文集, 1990, 625, 628, 1990年09月
  日本語
• 螺旋銅管コイルを製氷エレメントとした氷蓄熱槽に関する実験研究 (その1) 氷蓄熱槽の概要と熱的性能確認実験結果
  八十田茂; 田中俊六; 鈴木定彦; 深谷俊英, 日本建築学会学術講演梗概集D 環境工学, 1990, 1157, 1158, 1990年09月
  一般社団法人日本建築学会, 日本語
• 特集 イディオタイプをめぐって イディオタイプ特異性T細胞の活性化とその意義
  鈴木定彦; 依田知子; 坂戸信夫, 臨床免疫, 22, 8, 1087, 1097, 1990年08月
  科学評論社, 日本語
• 鈴木定彦、依田知子、坂戸信夫 イデオタイプ特異性T細胞の活性化とその意義
  臨床免疫, 22, 1087, 1097, 1990年
• 抗イディオタイプ抗体の抗腫よう作用と癌免疫療法への応用
  扇間昌規; 鈴木定彦; 藤尾啓; 坂戸信夫, Biotherapy (Tokyo), 3, 6, 1415, 1429, 1989年12月
  日本語
• イディオタイプ処理・提示機構 II ストップフロー法による解析
  坂戸信夫; 宇都宮直子; 中西守; 鈴木定彦; 藤尾啓; 荒田洋治, 日本免疫学会総会・学術集会記録, 19, 388, 1989年10月
  日本語
• イディオタイプ処理・提示機構 I 抗イディオタイプT細胞ハイブリドーマと合成イディオトープによる解析
  鈴木定彦; RUGDECH P; 大田明生; 依田知子; 藤尾啓; 坂戸信夫, 日本免疫学会総会・学術集会記録, 19, 387, 1989年10月
  日本語
• 氷蓄熱冷暖房システムに関する実験研究 II 低湿度高温度空調の体感実験
  田中俊六; 鈴木定彦; 八十田茂; 深谷俊英; 杉山一朗; 野村知宏, 空気調和・衛生工学会学術講演会講演論文集, 1989, 485, 488, 1989年09月
  日本語
• 氷蓄熱冷暖房システムに関する実験研究 I 実験設備の概要と冷房実験結果
  田中俊六; 鈴木定彦; 本田和幸; 杉山一朗; 八十田茂; 深谷俊英, 空気調和・衛生工学会学術講演会講演論文集, 1989, 481, 484, 1989年09月
  日本語
• 氷蓄熱冷暖房システムに関する実験研究 III 暖房時早朝予熱運転の効果
  田中俊六; 鈴木定彦; 八十田茂; 深谷俊英; 菊田道宣, 空気調和・衛生工学会学術講演会講演論文集, 1989, 489, 492, 1989年09月
  日本語
• 氷蓄熱冷暖房システムに関する実験研究 IV オフィスビルへの適用に関する考察
  田中俊六; 鈴木定彦; 八十田茂; 杉山一朗, 空気調和・衛生工学会学術講演会講演論文集, 1989, 493, 496, 1989年09月
  日本語
• 扇間昌規、鈴木定彦、藤尾啓、坂戸信夫 抗イデオタイプ抗体の抗腫瘍作用と癌免疫療法への応用
  Biotherapy, 3, 1415, 1429, 1989年
• PRIMARY STRUCTURE OF RAT-BRAIN PROSTAGLANDIN-D SYNTHETASE DEDUCED FROM CDNA SEQUENCE
  Y URADE; A NAGATA; Y SUZUKI; Y FUJII; O HAYAISHI, JOURNAL OF BIOLOGICAL CHEMISTRY, 264, 2, 1041, 1045, 1989年01月
  英語
• COMPLETE NUCLEOTIDE-SEQUENCE OF THE 16S RIBOSOMAL-RNA GENE OF MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; A NAGATA; Y ONO; T YAMADA, JOURNAL OF BACTERIOLOGY, 170, 6, 2886, 2889, 1988年06月
  英語, 記事・総説・解説・論説等（学術雑誌）
• 鈴木定彦、山田毅 Mycobacterium phleiのリボゾームRNA遺伝子の解析
  鈴木定彦; 山田毅, 結核, 63, 1, 1, 3, 1988年
• Study on rRNA Genes in Mycobacterium smegmatis
  Microbiol Immunol, 32, 1259, 1262, 1988年
• The nucleotide sequence of 16S rRNA gene from Streptomyces lividans TK21
  SUZUKI Y., Nucleic Acids Res., 16, 1, 370, 370, 1988年
• CHLORELLA CHLOROPLAST DNA-SEQUENCE CONTAINING A GENE FOR THE LARGE SUBUNIT OF RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE OXYGENASE AND A PART OF A POSSIBLE GENE FOR THE BETA'-SUBUNIT OF RNA-POLYMERASE
  K YOSHINAGA; T OHTA; Y SUZUKI; M SUGIURA, PLANT MOLECULAR BIOLOGY, 10, 3, 245, 250, 1988年
  英語
• Mycobacterium phleiのリボソームRNA遺伝子の解析
  鈴木定彦; 山田毅, 結核, 63, 1, 1, 3, 1988年
  英語
• THE NUMBER OF RIBOSOMAL-RNA GENES IN MYCOBACTERIUM-LEPRAEMURIUM
  Y SUZUKI; T MORI; Y MIYATA; T YAMADA, FEMS MICROBIOLOGY LETTERS, 44, 1, 73, 76, 1987年09月
  英語
• ORGANIZATION OF RIBOSOMAL-RNA GENES IN MYCOBACTERIUM-BOVIS BCG
  Y SUZUKI; K YOSHINAGA; Y ONO; A NAGATA; T YAMADA, JOURNAL OF BACTERIOLOGY, 169, 2, 839, 843, 1987年02月
  英語
• 抗酸菌に於ける蛋白合成阻害剤への耐性獲得機構とその作用機序及びリボソームの研究
  山田毅; 鈴木定彦, 日本放線菌学会会誌, 49, 10, 14, 1986年12月
  日本語
• 鈴木定彦、山田毅 抗酸菌における蛋白合成阻害剤への耐性獲得機構とその作用機及びリボゾームの研究
  放線菌学会誌, 49, 10, 14, 1986年
• ALTERATION OF RIBOSOMES AND RNA-POLYMERASE IN DRUG-RESISTANT CLINICAL ISOLATES OF MYCOBACTERIUM-TUBERCULOSIS
  T YAMADA; A NAGATA; Y ONO; Y SUZUKI; T YAMANOUCHI, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 27, 6, 921, 924, 1985年
  英語
• "N-ACETYLNEURAMINYLLACTOSYLCERAMIDE, GM3-NEUAC, A NEW INFLUENZA-A VIRUS RECEPTOR WHICH MEDIATES THE ADSORPTION-FUSION PROCESS OF VIRAL-INFECTION - BINDING-SPECIFICITY OF INFLUENZA-VIRUS A/AICHI/2/68 (H3N2) TO MEMBRANE-ASSOCIATED GM3 WITH DIFFERENT MOLECULAR-SPECIES OF SIALIC-ACID
  Y SUZUKI; M MATSUNAGA; M MATSUMOTO, JOURNAL OF BIOLOGICAL CHEMISTRY, 260, 3, 1362, 1365, 1985年
  英語, 記事・総説・解説・論説等（学術雑誌）
• RAPID PREPARATION OF PLASMID BY GEL-PERMEATION CHROMATOGRAPHY ON TOYOPEARL HW75S
  K YOSHINAGA; Y SUZUKI, AGRICULTURAL AND BIOLOGICAL CHEMISTRY, 47, 4, 919, 920, 1983年
  英語, 記事・総説・解説・論説等（学術雑誌）
• 屋根一体形空気集熱器と利用システム
  田中俊六; 鈴木定彦; 多賀和夫, 太陽エネルギー, 7, 2, 13, 20, 1981年07月01日
  日本語
• 病院使用水量の幾つかの考察
  鈴木定彦, 建築設備と配管工事, 17, 5, 74, 82, 1979年
  日本語
• 屋根一体形空気式集熱器について
  田中俊六; 鈴木定彦; 多賀和夫, 日本太陽エネルギー学会研究発表会講演論文集, 5th, 33, 36, 1979年
  日本語
• 都営住宅団地使用水量研究 IV 基準値の検討
  鈴木定彦; 佐藤光男; 高地進; 紀谷文樹; 高橋紀行, 空気調和・衛生工学会学術講演会講演論文集, 1975, 185, 188, 1975年
  日本語
• 都営住宅団地使用水量研究 III 各戸と共用水せんの使用水量
  鈴木定彦; 佐藤光男; 高地進; 紀谷文樹; 高橋紀行, 空気調和・衛生工学会学術講演会講演論文集, 1975, 181, 184, 1975年
  日本語
• 都営住宅団地使用水量研究 I 調査概要
  紀谷文樹; 佐藤光男; 鈴木定彦; 高地進; 高橋紀行, 空気調和・衛生工学会学術講演会講演論文集, 1975, 173, 176, 1975年
  日本語
• 都営住宅団地使用水量研究 II 全体水量とアンケート
  紀谷文樹; 佐藤光男; 鈴木定彦; 高地進; 高橋紀行, 空気調和・衛生工学会学術講演会講演論文集, 1975, 177, 180, 1975年
  日本語
• 温度成層型蓄熱そうに関する研究 I 蓄熱そうの熱特性に関する実験
  田中俊六; 鈴木定彦; 中村賢五, 日本建築学会大会学術講演梗概集 計画系, 1972, 229, 230, 1972年
  日本語
• 温度成層型蓄熱そうに関する研究 II 蓄熱そうの建設費
  田中俊六; 佐藤光男; 鈴木定彦, 日本建築学会大会学術講演梗概集 計画系, 1972, 231, 232, 1972年
  日本語
• 温度成層型蓄熱そうに関する研究 III 蓄熱式地域冷暖房への適用
  田中俊六; 佐藤光男; 鈴木定彦; 中村賢五, 日本建築学会大会学術講演梗概集 計画系, 1972, 233, 234, 1972年
  日本語
• 高層住宅の中央暖房の方向
  田中俊六; 鈴木定彦, 日本建築学会大会学術講演梗概集 計画系, 1971, 215, 216, 1971年
  日本語