研究者基本情報

• 博士 (獣医学), 酪農学園大学, 2013年04月

• https://researchmap.jp/satoto

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201801019683823989
• https://vethygiene.vetmed.hokudai.ac.jp

• 201801019683823989

• One Health
• 伴侶動物由来耐性菌
• 細菌感染症創薬
• 生体内発育必須因子 (vivoEF)
• コリスチン耐性
• チゲサイクリン耐性
• フルオロキノロン耐性
• 薬剤耐性

• ライフサイエンス, 細菌学, 薬剤耐性

• 学士課程, 獣医学部
• 博士課程, 国際感染症学院

研究活動情報

• 2024年11月, 農林水産省, 若手農林水産研究者表彰
  佐藤 豊孝
• 2024年01月, 米国微生物学会 (ASM), ASM Country Ambassador of Science
  Toyotaka Sato
• 2022年10月, 北海道大学 第8回部局横断シンポジウム「新たな学際領域を生み出す異分野融合研究」, ベストプレゼンター賞
  多剤耐性菌の克服に向けた新たなアプローチ 感染部位特異的細菌感染症治療法の開発
  佐藤 豊孝
• 2021年03月, 日本細菌学会, 黒屋奨学賞
  佐藤 豊孝
• 2019年, 日本細菌学会北海道支部会, 最優秀演題賞
  佐藤 豊孝
• 2018年03月, 米国微生物学会, Young Ambassador Microbe Travel Award
  佐藤 豊孝
• 2017年03月, 米国微生物学会, Young Ambassador Microbe Travel Award
  佐藤 豊孝
• 2017年, 米国微生物学会, ASM Young Ambassador of Science
  佐藤 豊孝
• 2015年, 日本細菌学会北海道支部会, 優秀演題賞
  佐藤 豊孝
• 2012年, 北海道獣医師会, 地区学会長賞
  佐藤 豊孝
• 2012年, 日本細菌学会北海道支部会, 最優秀演題賞
  佐藤 豊孝
• 2011年, 日本細菌学会北海道支部会, ベストプレゼンテーション賞
  佐藤 豊孝

• Symbiont- and Bacterial Cell Size-dependent Backpacking and Grazing of Acanthamoeba.
  Nana Tanaka; Kotoka Kuriki; Torahiko Okubo; Yoshiaki Enoeda; Ayano Konno; Shinji Nakamura; Toyotaka Sato; Shin-Ichi Yokota; Hiroyuki Yamaguchi
  Microbes and environments, 41, 1, 2026年, ［国内誌］
  英語, 研究論文（学術雑誌）, On solid media, Acanthamoeba harboring the endosymbiotic bacterium (Neochlamydia) carries live Escherichia coli on its cell surface without phagocytosing this bacterium, and defends against infection by Legionella pneumophila of a small size in an endosymbiotic bacterium-dependent manner. This implies the presence of an unknown protective mechanism. Therefore, we exami-ned the physical properties of the carried bacteria using transposon insertion mutants that had lost the "backpack" on solid media. A mutant was selected from a library in which the nhaA gene, encoding a Na+/H+ antiporter, was disrupted. The knockout mutant was longer than the parental strain and was gradually consumed by symbiotic amoebae. Similarly, the NhaA-knockout mutant strain was longer and lacked the backpack. The complementation of nhaA restored bacterial cells to their normal size, and the backpack phenomenon reappeared. Using E. coli elongated by a treatment with mitomycin C, the backpack was not evident, and enlarged bacteria were consumed by symbiotic amoebae. Therefore, symbiotic amoebae protected themselves from intruders by not engulfing small bacteria in an endosymbiosis-dependent manner. The present results propose a novel countermeasure by phagocytic cells against intruders that involves the recognition of bacterial sizes and is dependent on endosymbiosis.
• Antimicrobial Susceptibility of Campylobacter spp. Isolated from Cattle in Mongolia
  Erdenebat Bulgan; Zolzaya Byambajav; Batsukh Naranchimeg; Batsaikhan Chantsal; Tsognemekh Bolormaa; Badrakh Sandagdorj; Purevdorj Nyam-Osor; Eisaku Kikuchi; Akio Suzuki; Jirachaya Toyting-Hiraishi; Toyotaka Sato; Motohiro Horiuchi
  Veterinary Sciences, 12, 10, 931, 931, MDPI AG, 2025年09月24日
  研究論文（学術雑誌）, Poultry and cattle are the major reservoirs of Campylobacter infection in humans. However, no information is available on Campylobacter spp. in cattle in Mongolia. Thus, this study aimed to assess their prevalence and antimicrobial resistance. Between 2019 and 2023, rectal swabs were collected from cattle on dairy farms around Ulaanbaatar city and in total, 35 Campylobacter spp., including 23 C. jejuni, 7 C. hyointestinalis, 4 C. fetus, and 1 C. lari, were isolated. Multilocus sequence typing of C. jejuni cattle isolates revealed substantial genetic diversity and identified 7 sequence types (STs) including ST61, which is known to be associated with cattle and sheep. Interestingly, the antimicrobial resistance patterns of the C. jejuni cattle isolates completely differed from those of previously reported chicken isolates. Excluding one ciprofloxacin-resistant isolate, all isolates were susceptible to tetracycline and ciprofloxacin. This is the first report on the characterization of Campylobacter spp. in cattle in Mongolia. Although no official statistics of human campylobacteriosis are currently available in Mongolia, data on Campylobacter spp. in food-producing animals represent valuable information for investigating potential sources and infection routes to humans.
• Potential human health risk of carbapenem-non-susceptible Pseudomonas aeruginosa from companion animals.
  Jirachaya Toyting-Hiraishi; Toyotaka Sato; Mana Tohyama; Taro Fujino; Kaho Okada; Kazuyoshi Sasaoka; Nozomu Yokoyama; Kana Torii; Akio Suzuki; Yuzo Tsuyuki; Kensuke Nakamura; Mitsuyoshi Takiguchi; Motohiro Horiuchi
  The Journal of Antimicrobial Chemotherapy, 2025年09月19日, ［査読有り］, ［責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND AND OBJECTIVES: The close bond between companion animals and humans may accelerate the spread of antimicrobial-resistant bacteria. Pseudomonas aeruginosa, an opportunistic pathogen in both, poses a public health threat due to antimicrobial resistance (AMR) and diverse virulence factors. However, One Health-based comparison remains limited. This study investigated the current AMR status and molecular characteristics of P. aeruginosa in companion animals in Japan to assess potential human health risks. METHODS: We examined 197 P. aeruginosa clinical isolates from companion animals [dogs (n = 99) and cats (n = 98)] across Japan in 2024. Antimicrobial susceptibility to human clinical antibiotics was evaluated. In carbapenem-non-susceptible isolates, multilocus sequence typing and detection of resistance genes and virulence factors were performed. RESULTS: Ciprofloxacin (20.3%) and piperacillin (10.7%) showed the highest resistance rates, with 5.6% of isolates being multidrug-resistant. Carbapenem resistance rates were 6.1% for imipenem and 1.0% for meropenem. Thirty-five isolates (17.8%) exhibited carbapenem non-susceptibility but remained susceptible to cefepime, ciprofloxacin, or amikacin. Of 27 identified sequence types, 20 (77.1% of carbapenem-non-susceptible isolates) were known in humans, including two high-risk clones (ST233 and ST298; 8.6%) reported for the first time in Japanese companion animals. These isolates carried mutations in efflux pump-related genes and multiple virulence factors. One showed close genetic relatedness to a human isolate, suggesting possible interspecies transmission. CONCLUSIONS: Our findings highlight the potential cross-species transmission risk of antimicrobial-resistant P. aeruginosa. Identification of shared high-risk clones with multiple virulence factors emphasizes the need for continuous vigilance and actions within the One Health framework.
• Prevalence, antimicrobial susceptibility, and virulence profiles of fluoroquinolone-resistant Escherichia coli isolated from companion animals in Sapporo, Japan.
  Aiko Maeda; Toyotaka Sato; Jirachaya Toyting-Hiraishi; Akio Suzuki; Yuuji Hoshino; Shingo Torigoe; Keiichiro Sakakibara; Satoshi Tamai; Tooru Tachibana; Motohiro Horiuchi
  The Journal of veterinary medical science, 2025年09月16日, ［査読有り］, ［責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, Antimicrobial resistance in Escherichia coli is a growing concern in both human and veterinary medicine. Although fluoroquinolone-resistant (FQ-R) E. coli has been reported in companion animals, no integrated analysis incorporating antimicrobial susceptibility, clonality, resistance genes, and virulence factors (VFs) to assess human health risks has been conducted in Japan. This study aimed to characterize FQ-R E. coli isolates from companion animals in Sapporo, Japan by identifying antimicrobial susceptibility, clonality, resistance genes, and VFs. Among 106 animals sampled, 33.0% carried FQ-R E. coli. Among 104 FQ-R E. coli isolates, 58 isolates (55.8%) were identified as ST131. Whole-genome sequencing of 35 representative FQ-R E. coli isolates, including 20 ST131 isolates, showed that the ST131 isolates were distributed among five clades/sub-clades (C1-nM27, C1-M27, A, C2 and Unclassified), indicating increased clade diversity compared to previous years. ST1193, another international high-risk clone, was also detected. All isolates harbored mutations of quinolone resistance-determining regions in gyrA and parC, and 51.4% carried blaCTX-M genes, including blaCTX-M-27 and blaCTX-M-14. Most isolates remained susceptible to aminoglycosides and cefmetazole, although the latter is not approved for veterinary use in Japan. Additionally, 72 VFs were identified, and eight were shared by all isolates, suggesting potential risk to human health. Our findings indicate that companion animals share certain E. coli lineages including ST131 and ST1193 with humans. Prudent antimicrobial use and routine hygiene practices are essential to limit the transmission. Further studies incorporating human and environmental isolates are needed to better understand the transmission dynamics of FQ-R E. coli within communities.
• Design, Synthesis, and Biological Evaluation of Lipid-Modified Derivatives of Tunicamycins.
  Kazuki Yamamoto; Toyotaka Sato; Ellene H Mashalidis; Seok-Yong Lee; Motohiro Horiuchi; Satoshi Ichikawa
  Chemistry (Weinheim an der Bergstrasse, Germany), e02296, 2025年09月15日, ［査読有り］, ［責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Naturally occurring antibiotic tunicamycin targets bacterial peptidoglycan biosynthesis by inhibiting bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY), but it also inhibits human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT), leading to cytotoxicity. This study thoroughly investigated the structure-activity relationship of the fatty acyl side chain of tunicamycin to develop MraY-selective inhibitors, based on structural differences between MraY and GPT. Longer alkyl chains and flexible structures were found to favor MraY inhibitory activity, and benzene rings were acceptable for binding. The hybrid analogue containing oleoyl group, which contributed most significantly to MraY inhibitory activity, and the MurNAc moiety, which is important for MraY-selective inhibition, showed enhanced MraY inhibitory activity as well as improved antibacterial activity against S. aureus and E. faecium.
• Structure-Activity Relationship of Pseudouridimycin Focusing on the Improvement of Chemical Stability.
  Ryotaro Okawa; Irina Artsimovitch; Akira Katsuyama; Toyotaka Sato; Courtney C Aldrich; Satoshi Ichikawa
  Journal of medicinal chemistry, 68, 15, 15461, 15482, 2025年08月14日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, In recent years, the spread of drug-resistant bacterial infections has driven a critical demand for new antimicrobial agents with novel mechanisms of action. Pseudouridimycin (PUM) is a nucleoside antibiotic that inhibits bacterial DNA-dependent RNA polymerase (RNAP) by binding in the conserved active site that is distinct from the mutable allosteric sites targeted by the clinically approved rifamycin-class of antibiotics. However, translational development of PUM is compromised by its poor intrinsic chemical stability and competitive modality of inhibition with respect to UTP, which will require further augmentation of binding affinity. We have conducted structure-activity relationship (SAR) studies on PUM by approaching these two problems through the rational design of analogs based on the known PUM·RNAP X-ray cocrystal structure and through elucidation of the decomposition mechanisms.
• 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, 2025年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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), blaTEM-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 blaCTX-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.
• 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, ［査読有り］, ［責任著者］, ［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.
• Bacillaceae serine proteases and Streptomyces epsilon-poly-L-lysine synergistically inactivate Caliciviridae by inhibiting RNA genome release.
  Soh Yamamoto; Noriko Ogasawara; Yuka Sudo-Yokoyama; Sachiko Sato; Nozomu Takata; Nana Yokota; Tomomi Nakano; Kyoko Hayashi; Akira Takasawa; Mayumi Endo; Masako Hinatsu; Keitaro Yoshida; Toyotaka Sato; Satoshi Takahashi; Kenichi Takano; Takashi Kojima; Jun Hiraki; Shin-Ich Yokota
  Scientific reports, 14, 1, 15181, 15181, 2024年07月02日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-L-lysine (EPL) produced by Streptomyces-a natural antimicrobial-elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.
• Characterization of Shiga Toxin-producing Escherichia coli Isolated from Cattle Around Ulaanbaatar City, Mongolia.
  Erdenebat Bulgan; Zolzaya Byambajav; Narantuya Ayushjav; Yuji Hirai; Misaki Tanaka; Nyam-Osor Purevdorj; Sandagdorj Badrakh; Akio Suzuki; Yusuke Komatsu; Toyotaka Sato; Motohiro Horiuchi
  Journal of food protection, 87, 7, 100294, 100294, 2024年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Shiga toxin-producing Escherichia coli (STEC) are associated with severe infections including hemorrhagic colitis and hemolytic uremic syndrome in humans. Ruminants are known as reservoirs of STEC; however, no data are available on STEC in ruminants in Mongolia, where more than 5 million cattle and 25 million sheep are raised. To disclose the existence and characteristics of STEC in Mongolia, in this study, we isolated and characterized STEC from cattle in Mongolia. We collected 350 rectal swabs of cattle from 30 farms near Ulaanbaatar city and isolated 45 STEC from 21 farms. Rectal swabs were precultured with modified Escherichia coli broth and then inoculated to Cefixime-Tellurite Sorbitol MacConkey agar plate and/or CHROMagar STEC agar plate for the isolation of STEC. The isolation ratios in each farm were from 0% to 40%. Multiplex PCR for the estimation of O- and H-serotypes identified 12 O-genotypes (Og-types) and 11 H-genotypes (Hg-types) from 45 isolates; however, Og-types of 19 isolates could not be determined. Stx gene subtyping by PCR identified 2 stx1 subtypes (1a and 1c) and 4 stx2 subtypes (2a, 2c, 2d, and 2g). Forty-five isolates were divided into 21 different groups based on the Og- and Hg-types, stx gene subtypes and the existence of virulence factors, ehxA, eae, and saa, which includes several major serotypes associated with human illness such as O26:H11 and O157:H7. The most dominant isolate, OgUT:H19 [stx1a (+), stx2a (+), ehxA (+) and saa (+)], was isolated from eight farms. This is the first report on the characterization of STEC in cattle in Mongolia, and the results suggest the importance of further monitoring of STEC contamination in the food chains as well as STEC infection in humans.
• Development of a natural product optimization strategy for inhibitors against MraY, a promising antibacterial target.
  Kazuki Yamamoto; Toyotaka Sato; Aili Hao; Kenta Asao; Rintaro Kaguchi; Shintaro Kusaka; Radhakrishnam Raju Ruddarraju; Daichi Kazamori; Kiki Seo; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Seok-Yong Lee; Satoshi Ichikawa
  Nature communications, 15, 1, 5085, 5085, 2024年06月14日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.
• Traces of pandemic fluoroquinolone-resistant Escherichia coli clone ST131 transmitted from human society to aquatic environments and wildlife in Japan
  Toyotaka Sato; Kojiro Uemura; Mitsuru Yasuda; Aiko Maeda; Toshifumi Minamoto; Kazuki Harada; Michiyo Sugiyama; Shiori Ikushima; Shin-ichi Yokota; Motohiro Horiuchi; Satoshi Takahashi; Testuo Asai
  One Health, 18, 100715, 100715, Elsevier BV, 2024年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Transmission of antimicrobial-resistant bacteria among humans, animals, and the environment is a growing concern worldwide. The distribution of an international high-risk fluoroquinolone-resistant Escherichia coli clone, ST131, has been documented in clinical settings. However, the transmission of ST131 from humans to surrounding environments remains poorly elucidated. To comprehend the current situation and identify the source of ST131 in nature, we analyzed the genetic features of ST131 isolates from the aquatic environment (lake/river water) and wildlife (fox, raccoon, raccoon dog, and deer) and compared them with the features of isolates from humans in Japan using accessory and core genome single nucleotide polymorphism (SNP) analyses. We identified ST131 isolates belonging to the same phylotype and genome clusters (four of eight clusters were concomitant) with low SNP distance between the human isolates and those from the aquatic environment and wildlife. These findings warn of ST131 transmission between humans and the surrounding environment in Japan.
• Antimicrobial resistance and self-reported hand hygiene awareness before and after an infection prevention and control programme: A 7-year analysis in a small animal veterinary teaching hospital.
  Kazuyoshi Sasaoka; Toyotaka Sato; Keitaro Morishita; Kenji Hosoya; Nozomu Yokoyama; Takachika Sato; Motohiro Horiuchi; Mitsuyoshi Takiguchi
  Veterinary journal (London, England : 1997), 306, 106154, 106154, 2024年05月31日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Infection prevention and control (IPC) in veterinary medicine is crucial to protect patients, owners, staff, and the public. An IPC programme is recommended for every animal hospital. The objective of this retrospective longitudinal study was to describe the changes in bacterial and multidrug-resistant (MDR) bacterial isolates and self-reported hand hygiene awareness and practices after an IPC programme to assess the long-term effect of this programme in small animal veterinary medicine. The IPC programme was implemented at our veterinary teaching hospital in April 2018, which included the establishment of an infection control task force, regular IPC lectures and poster campaigns, infrastructure improvement, and manual refinement. Laboratory-based surveillance was retrospectively conducted before and after the programme (January 2016-December 2022). Level and slope changes in bacterial isolates were evaluated using interrupted time-series analysis. Self-reported hand hygiene awareness and practices were assessed using an annual questionnaire. Additionally, hygiene product purchases during the study period were investigated. The monthly number of total and MDR bacterial isolates decreased significantly after the programme (MDR level change: -0.426; 95% confidence interval: -0.744, -0.109; P = 0.009; and MDR slope change: -0.035; 95% confidence interval: -0.058, -0.011; P = 0.003). Additionally, awareness of hand hygiene before touching animals improved after the programme. Overall self-reported hand hygiene practices improved, and hygiene product purchases significantly increased. These results suggested that the IPC programme may have long-term effects regarding reducing total and MDR bacterial isolates and improving hand hygiene awareness in veterinary medicine.
• 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, ［査読有り］, ［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.
• Affinity of β-Lactam Antibiotics for Neisseria gonorrhoeae Penicillin-Binding Protein 2 Having Wild, Cefixime-Reduced-Susceptible, and Cephalosporin (Ceftriaxone)-Resistant penA Alleles.
  Yoshiki Hiyama; Soh Yamamoto; Toyotaka Sato; Noriko Ogasawara; Naoya Masumori; Satoshi Takahashi; Shin-Ichi Yokota
  Microbial drug resistance (Larchmont, N.Y.), 30, 3, 141, 146, 2024年01月12日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Multidrug-resistant Neisseria gonorrhoeae is a serious concern worldwide. Resistance to β-lactam antibiotics occurs through mutations in penicillin-binding proteins (PBPs), acquisition of β-lactamases, and alteration of antibiotic penetration. Mosaic structures of penA, which encodes PBP2, play a major role in resistance to β-lactams, especially cephalosporins. Ceftriaxone (CRO) is recognized as the only satisfiable antibiotic for the treatment of gonococcal infections; however, CRO-resistant isolates have emerged in the community. Here, we examined the affinity of β-lactam antibiotics for recombinant PBP2 in a competition assay using fluorescence-labeled penicillin. We found no or little difference in the affinities of penicillins and meropenem (MEM) for PBP2 from cefixime (CFM)-reduced-susceptible strain and cephalosporin-resistant strain. However, the affinity of cephalosporins, including CRO, for PBP2 from the cephalosporin-resistant strain was markedly lower than that for PBP2 from the CFM-reduced-susceptible-resistant strain. Notably, piperacillin (PIP) showed almost the same affinity for PBP2 from penicillin-susceptible, CFM-reduced-susceptible, and cephalosporin (including CRO)-resistant strains. Thus, PIP/tazobactam and MEM are candidate antibiotics for the treatment of CRO-resistant/multidrug-resistant N. gonorrhoeae.
• Excitatory neuron-prone prion propagation and excitatory neuronal loss in prion-infected mice.
  Temuulen Erdenebat; Yusuke Komatsu; Nozomi Uwamori; Misaki Tanaka; Takashi Hoshika; Takeshi Yamasaki; Ayano Shimakura; Akio Suzuki; Toyotaka Sato; Motohiro Horiuchi
  Frontiers in molecular neuroscience, 17, 1498142, 1498142, 2024年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The accumulation of a disease-specific isoform of prion protein (PrPSc) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrPSc and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection. However, the underlying mechanism is largely unknown. In this study, we provided evidence that the prion 22L strain propagates more efficiently in excitatory neurons than inhibitory neurons and that excitatory neurons in the thalamus are vulnerable to prion infection. PrPSc accumulation was less intense in the striatum, where GABAergic inhibitory neurons predominate, compared to the cerebral cortex and thalamus, where glutamatergic excitatory neurons are predominant, in mice intracerebrally or intraperitoneally inoculated with the 22L strain. PrPSc stains were observed along the needle track after stereotaxic injection into the striatum, whereas they were also observed away from the needle track in the thalamus. Consistent with inefficient prion propagation in the striatum, the 22L prion propagated more efficiently in glutamatergic neurons than GABAergic neurons in primary neuronal cultures. RNAscope in situ hybridization revealed a decrease in Vglut1- and Vglut2-expressing neurons in the ventral posterolateral nuclei of the thalamus in 22L strain-infected mice, whereas no decrease in Vgat-expressing neurons was observed in the adjacent reticular nucleus, mainly composed of Vgat-expressing interneurons. The excitatory neuron-prone prion propagation and excitatory neuronal loss in 22L strain-infected mice shed light on the neuropathological mechanism of prion diseases.
• Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan.
  Shin-Ichi Yokota; Naoyuki Tsukamoto; Toyotaka Sato; Yasuo Ohkoshi; Soh Yamamoto; Noriko Ogasawara
  IJID regions, 8, 105, 110, 2023年09月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: It is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. METHODS: We determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. RESULTS: Vaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. CONCLUSION: The progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.
• 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, ［査読有り］, ［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.
• 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.
• Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan.
  Yutaro Nagano; Koji Kuronuma; Yasuo Kitamura; Kanami Nagano; Hayato Yabe; Sayaka Kudo; Toyotaka Sato; Shinya Nirasawa; Mami Nakae; Motohiro Horiuchi; Shin-Ichi Yokota; Yoshihiro Fujiya; Atsushi Saito; Satoshi Takahashi; Hirofumi Chiba
  Infection control and hospital epidemiology, 44, 11, 1, 7, 2023年04月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. METHODS: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. RESULTS: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital's faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. CONCLUSIONS: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.
• 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, ［査読有り］, ［国際誌］
  英語
• Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry
  Rintaro Kaguchi; Akira Katsuyama; Toyotaka Sato; Satoshi Takahashi; Motohiro Horiuchi; Shin-ichi Yokota; Satoshi Ichikawa
  Journal of the American Chemical Society, 145, 6, 3665, 3681, American Chemical Society (ACS), 2023年01月28日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Peptides can be converted to highly active compounds by introducing appropriate substituents on the suitable amino acid residue. Although modifiable residues in peptides can be systematically identified by peptide scanning methodologies, there is no practical method for optimization at the "scanned" position. With the purpose of using derivatives not only for scanning but also as a starting point for further chemical functionalization, we herein report the "scanning and direct derivatization" strategy through chemoselective acylation of embedded threonine residues by a serine/threonine ligation (STL) with the help of in situ screening chemistry. We have applied this strategy to the optimization of the polymyxin antibiotics, which were selected as a model system to highlight the power of the rapid derivatization of active scanning derivatives. Using this approach, we explored the structure-activity relationships of the polymyxins and successfully prepared derivatives with activity against polymyxin-resistant bacteria and those with Pseudomonas aeruginosa selective antibacterial activity. This strategy opens up efficient structural exploration and further optimization of peptide sequences.
• Human pathogenic bacteria on high-touch dry surfaces can be controlled by warming to human-skin temperature under moderate humidity.
  Ayano Konno; Torahiko Okubo; Yoshiaki Enoeda; Tomoko Uno; Toyotaka Sato; Shin-Ichi Yokota; Rika Yano; Hiroyuki Yamaguchi
  PloS one, 18, 9, e0291765, 2023年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Healthcare-associated infections have become a major health issue worldwide. One route of transmission of pathogenic bacteria is through contact with "high-touch" dry surfaces, such as handrails. Regular cleaning of surfaces with disinfectant chemicals is insufficient against pathogenic bacteria and alternative control methods are therefore required. We previously showed that warming to human-skin temperature affected the survival of pathogenic bacteria on dry surfaces, but humidity was not considered in that study. Here, we investigated environmental factors that affect the number of live bacteria on dry surfaces in hospitals by principal component analysis of previously-collected data (n = 576, for CFU counts), and experimentally verified the effect of warming to human-skin temperature on the survival of pathogenic bacteria on dry surfaces under humidity control. The results revealed that PCA divided hospital dry surfaces into four groups (Group 1~4) and hospital dry surfaces at low temperature and low humidity (Group 3) had much higher bacterial counts as compared to the others (Group 1 and 4) (p<0.05). Experimentally, warming to human-skin temperature (37°C with 90% humidity) for 18~72h significantly suppressed the survival of pathogenic bacteria on dry surfaces, such as plastic surfaces [p<0.05 vs. 15°C (Escherichia coli DH5α, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and blaNDM-5 E. coli)] or handrails [p<0.05 vs. 15~25°C (E. coli DH5α, S. aureus, P. aeruginosa, A. baumannii)], under moderate 55% humidity. Furthermore, intermittent heating to human-skin temperature reduced the survival of spore-forming bacteria (Bacillus subtilis) (p<0.01 vs. continuous heating to human-skin temperature). NhaA, an Na+/H+ antiporter, was found to regulate the survival of bacteria on dry surfaces, and the inhibitor 2-aminoperimidine enhanced the effect of warming at human-skin temperature on the survival of pathogenic bacteria (E. coli DH5α, S. aureus, A. baumannii) on dry surfaces. Thus, warming to human-skin temperature under moderate humidity is a useful method for impairing live pathogenic bacteria on high-touch surfaces, thereby helping to prevent the spread of healthcare-associated infections.
• Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.
  Takeshi Nakaya; Miyuki Yabe; Ellene H Mashalidis; Toyotaka Sato; Kazuki Yamamoto; Yuta Hikiji; Akira Katsuyama; Motoko Shinohara; Yusuke Minato; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Seok-Yong Lee; Satoshi Ichikawa
  Nature communications, 13, 1, 7575, 7575, 2022年12月20日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria.
• Chromosomal coharboring of blaIMP-60 and mcr-9 in Enterobacter asburiae isolated from a Japanese woman with empyema: a case report.
  Yusuke Miyazato; Noriko Iwamoto; Masaru Usui; Toyotaka Sato; Tohru Miyoshi-Akiyama; Maki Nagashima; Kazuhisa Mezaki; Kayoko Hayakawa; Norio Ohmagari
  BMC infectious diseases, 22, 1, 762, 762, 2022年09月30日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Polymyxin E (colistin) is a last-resort antibiotic to treat infections caused by carbapenemase-producing Enterobacteriaceae (CPE). However, reports of CPEs resistant to colistin have been increasing, and the mcr genes are emerging as resistance mechanisms. Among them, plasmid-mediate mcr-9 is known to be associated with colistin resistance, whereas reports on chromosomal mcr-9 and its association with colistin resistance in humans are few. CASE PRESENTATION: We identified Enterobacter asburiae harboring mcr-9 and blaIMP-60 in the pleural fluid of a patient with empyema. The long-read sequencing technique revealed that these genes were located on its chromosome. Despite the lack of exposure to colistin, the organism showed microcolonies in the inhibition circle in the E-test and disk diffusion test. Antibiotic susceptibility testing by broth microdilution confirmed its resistance to colistin. CONCLUSION: Our case report showed that mcr-9 can be present not only on plasmids but also on the chromosome in E. asburiae, and that the presence of mcr-9 on its chromosome may influence its susceptibility to colistin.
• A Hydroxypropyl Methylcellulose Plaque Assay for Human Respiratory Syncytial Virus.
  Yuka Takumi-Tanimukai; Soh Yamamoto; Noriko Ogasawara; Sayaka Nakabayashi; Katsumi Mizuta; Keisuke Yamamoto; Ryo Miyata; Takuya Kakuki; Sumito Jitsukawa; Toyotaka Sato; Hiroyuki Tsutsumi; Takashi Kojima; Kenichi Takano; Shin-Ichi Yokota
  Journal of virological methods, 304, 114528, 114528, 2022年03月28日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Quantifying proliferative virus particles is one of the most important experimental procedures in virology. Compared with classical overlay materials, newly developed cellulose derivatives enable a plaque-forming assay to produce countable clear plaques easily. HEp-2 cells are widely used in plaque assays for human respiratory syncytial virus (RSV). It is crucial to use an overlay material to keep HEp-2 cell proliferation and prevent RSV particles from spreading over the fluid. Among four cellulose derivatives, carboxymethyl cellulose sodium salt (CMC), hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and hydroxyethyl cellulose (HEC), we found that HPMC was the optimal overlay material because HPMC maintained HEp-2 cell proliferation and RSV infectivity. Although MCC was unsuitable for RSV, it assisted the plaque-forming by human metapneumovirus in TMPRSS2-expressing cells. Therefore, depending on the cells and viruses, it is necessary to use different overlay materials at varying concentrations.
• Solid-Phase Total Synthesis of Plusbacin A3.
  Kazuki Takashina; Akira Katsuyama; Rintaro Kaguchi; Kazuki Yamamoto; Toyotaka Sato; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Satoshi Ichikawa
  Organic letters, 24, 11, 2253, 2257, 2022年03月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The total synthesis of the depsipeptide natural product plusbacin A3 (1) utilizing solid-phase peptide synthesis (SPPS) was disclosed. A 3-hydroxy-proline derivative compatible with Fmoc SPPS was prepared by a diastereoselective Joullié-Ugi three-component reaction (JU-3CR)/hydrolysis sequence. After peptide elongation on the solid support, cleavage of the peptide from the resin, followed by macrolactamization and global deprotection, gave plusbacin A3 (1).
• Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing.
  Kenji Yokota; Takako Osaki; Shunji Hayashi; Shin-Ichi Yokota; Hiroaki Takeuchi; Emiko Rimbara; Hinako Ojima; Toyotaka Sato; Hideo Yonezawa; Keigo Shibayama; Kengo Tokunaga; Shigeru Kamiya; Kazunari Murakami; Mototsugu Kato; Toshiro Sugiyama
  Helicobacter, 27, 3, e12874, 2022年03月07日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Eradication treatment for Helicobacter pylori gastritis is covered by national health insurance since 2013 in Japan. However, eradication failure due to the increase of antimicrobial resistance has become a serious problem. The present study aims to establish a reference panel of Japanese H. pylori strains for antimicrobial susceptibility testing. METHOD: A total of 28 strains were collected from 4 medical facilities in Japan. Antimicrobial susceptibility tests (ASTs) to clarithromycin (CLR), amoxicillin (AMX), and metronidazole (MNZ), were used to select standard reference strains. Complete genome sequences were also determined. RESULTS: Three H. pylori strains (JSHR3, JSHR6 and JSHR31) were selected as standard reference strains by the Japanese Society for Helicobacter Research (JSHR). The minimum inhibitory concentrations (MICs) of the antibiotics against these 3 strains by agar dilution method with Brucella-based horse-serum-containing agar medium were as follows: JSHR3 (CLR 16 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), JSHR6 (CLR 0.016 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), and JSHR31 (CLR 16 μg/ml, AMX 1 μg/ml and MNZ 64 μg/ml). CONCLUSIONS: A reference panel of H. pylori JSHR strains was established. The panel consisted of JSHR6, which was antibiotic-susceptible, JSHR3, which was CLR-resistant, and JSHR31, which was multi-resistant. This reference panel will be essential for standardized ASTs before the optimal drugs are selected for eradication treatment.
• Corrigendum to "Design, synthesis and biological evaluation of simplified analogues of MraY inhibitory natural product with rigid scaffold" Bioorganic & Medicinal Chemistry 55 (2021) 116556.
  Kazuhiro Okamoto; Aoi Ishikawa; Ryotaro Okawa; Kazuki Yamamoto; Toyotaka Sato; Shin-Ichi Yokota; Kazuhiro Chiba; Satoshi Ichikawa
  Bioorganic & medicinal chemistry, 61, 116689, 116689, 2022年03月07日, ［査読有り］, ［国際誌］
  英語
• わが国における伴侶動物由来薬剤耐性菌の現状
  佐藤 豊孝; 田村 豊
  日本化学療法学会雑誌, 70, 2, 189, 199, (公社)日本化学療法学会, 2022年03月, ［査読有り］, ［筆頭著者, 責任著者］
  日本語
• Colistin Susceptibility in Companion Animal-Derived Escherichia coli, Klebsiella spp., and Enterobacter spp. in Japan: Frequent Isolation of Colistin-Resistant Enterobacter cloacae Complex.
  Toyotaka Sato; Kazuki Harada; Masaru Usui; Shin-Ichi Yokota; Motohiro Horiuchi
  Frontiers in cellular and infection microbiology, 12, 946841, 946841, 2022年, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Transmission of colistin-resistant Enterobacterales from companion animals to humans poses a clinical risk as colistin is a last-line antimicrobial agent for treatment of multidrug-resistant Gram-negative bacteria including Enterobacterales. In this study, we investigated the colistin susceptibility of 285 Enterobacterales (including 140 Escherichia coli, 86 Klebsiella spp., and 59 Enterobacter spp.) isolated from companion animals in Japan. We further characterized colistin-resistant isolates by multilocus sequence typing (MLST), phylogenetic analysis of hsp60 sequences, and population analysis profiling, to evaluate the potential clinical risk of companion animal-derived colistin-resistant Enterobacterales to humans in line with the One Health approach. All E. coli isolates were susceptible to colistin, and only one Klebsiella spp. isolate (1.2%, 1/86 isolates) was colistin resistant. Enterobacter spp. isolates were frequently colistin resistant (20.3%, 12/59 isolates). In colistin-resistant Enterobacter spp., all except one isolate exhibited colistin heteroresistance by population analysis profiling. These colistin-heteroresistant isolates belonged to clusters I, II, IV, VIII, and XII based on hsp60 phylogeny. MLST analysis revealed that 12 colistin-resistant Enterobacter spp. belonged to the Enterobacter cloacae complex; five Enterobacter kobei (four ST591 and one ST1577), three Enterobacter asburiae (one ST562 and two ST1578), two Enterobacter roggenkampii (ST606 and ST1576), and Enterobacter hormaechei (ST1579) and E. cloacae (ST765) (each one strain). Forty-two percent of the colistin-resistant E. cloacae complex isolates (predominantly ST562 and ST591) belonged to lineages with human clinical isolates. Four E. kobei ST591 isolates were resistant to third-generation cephalosporines, aminoglycosides, and fluroquinolones but remained susceptible to carbapenems. In conclusion, our study is the first to our knowledge to report the frequent isolation of the colistin-resistant E. cloacae complex from companion animals. Furthermore, a subset of isolates belonged to human-associated lineages with resistance to multiple classes of antibiotics. These data warrant monitoring carriage of the colistin-resistant E. cloacae complex in companion animals as part of a domestic infection control procedure in line with the One Health approach.
• Design, synthesis and biological evaluation of simplified analogues of MraY inhibitory natural product with rigid scaffold.
  Kazuhiro Okamoto; Aoi Ishikawa; Ryotaro Okawa; Kazuki Yamamoto; Toyotaka Sato; Shin-Ichi Yokota; Kazuhiro Chiba; Satoshi Ichikawa
  Bioorganic & medicinal chemistry, 55, 116556, 116556, 2021年12月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Muraymycins and caprazamycins are strong inhibitors of MraY, which is responsible for peptidoglycan biosynthesis. Although they are promising antibacterial agents with a novel mode of action, their chemical structures are rather complex. This study investigated the simplification of these natural products by structure-based drug design, synthesis, and biological evaluation. We developed a simplified rigid scaffold with an arylalkyne moiety, which shows sub-micromolar MraY inhibitory activity. The scaffold is suitable for further investigating the structure-activity relationship by virtue of our synthetic strategy, where the substituent of interest is installed in the last stage of synthesis. This scaffold shows the potential for further use in optimizing MraY inhibitory and antibacterial activities.
• Isolation of Human Lineage, Fluoroquinolone-Resistant and Extended-β-Lactamase-Producing Escherichia coli Isolates from Companion Animals in Japan.
  Toyotaka Sato; Shin-Ichi Yokota; Tooru Tachibana; Satoshi Tamai; Shigeki Maetani; Yutaka Tamura; Motohiro Horiuchi
  Antibiotics (Basel, Switzerland), 10, 12, 2021年11月28日, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, An increase in human and veterinary fluoroquinolone-resistant Escherichia coli is a global concern. In this study, we isolated fluoroquinolone-resistant E. coli isolates from companion animals and characterized them using molecular epidemiological analysis, multiplex polymerase chain reaction to detect E. coli ST131 and CTX-M type extended-spectrum β-lactamases (ESBL), and multi-locus sequence typing analysis. Using plain-CHROMagar ECC, 101 E. coli isolates were isolated from 34 rectal swabs of dogs and cats. The prevalence of resistance to fluoroquinolone and cefotaxime was 27.7% and 24.8%, respectively. The prevalence of fluoroquinolone-resistant isolates (89.3%) was higher when CHROMagar ECC with CHROMagar ESBL supplement was used for E. coli isolation. The prevalence of cefotaxime resistance was also higher (76.1%) when 1 mg/L of ciprofloxacin-containing CHROMagar ECC was used for isolation. The cefotaxime-resistant isolates possessed CTX-M type β-lactamase genes (CTX-M-14, CTX-M-15, or CTX-M-27). Seventy-five percent of fluoroquinolone-resistant isolates were sequence types ST131, ST10, ST1193, ST38, or ST648, which are associated with extensive spread in human clinical settings. In addition, we isolated three common fluoroquinolone-resistant E. coli lineages (ST131 clade C1-M-27, C1-nM27 and ST2380) from dogs and their respective owners. These observations suggest that companion animals can harbor fluoroquinolone-resistant and/or ESBL-producing E. coli, in their rectums, and that transmission of these isolates to their owners can occur.
• Reduction of susceptibility to azoles and 5-fluorocytosine and growth acceleration in Candida albicans in glucosuria.
  Yoshiki Hiyama; Toyotaka Sato; Satoshi Takahashi; Soh Yamamoto; Noriko Ogasawara; Naoya Masumori; Shin-Ichi Yokota
  Diagnostic microbiology and infectious disease, 102, 1, 115556, 115556, 2021年09月25日, ［査読有り］, ［責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and glucosuria, and is a risk factor for Candida infections. To reveal the potential effects of glucosuria on Candida spp., we investigated their growth and antifungal susceptibilities in normal human urine to which glucose was added. The viable cell numbers of Candida spp. were more than 10 fold higher in the urine added 3000 mg/dL glucose than in plain urine. In antifungal susceptibility, more than 80% of Candida albicans clinical isolates increased minimum inhibitory concentrations of azoles and 5-fluorocytosine with the addition of glucose, and exceeded their breakpoints. In most of the C. albicans clinical isolates, the mRNA expression of the azole resistance genes ERG11, CDR1, CDR2, and MDR1 in the presence of glucose in urine. These observations provide valuable information about the clinical course and therapeutic effects of azoles against C. albicans infections in patients with diabetes mellitus and hyperglucosuria.
• 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09日, ［査読有り］, ［責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Fluoroquinolone (FQ) and third-generation cephalosporin resistant Escherichia coli are increasing in Japan. In early 2000s, a FQ-resistant E. coli clone, sequence type (ST) 131, has been increased in clinical settings worldwide. It exhibits frequently ESBL producer, 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 isolated FQ-resistant E. coli clinical isolates from urine samples in 2020 (151 isolates), and compared with FQ-resistant E. coli collection isolated in 2008-2009. Identification of E. coli ST131 clades and blaCTX-M were determined by multiplex PCR. STs of non-ST131 isolates were determined by whole-genome sequence. 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 the ST131 increased from 27.3% in 2008-2009 to 64.3% in 2020. The blaCTX-M were found in 80.6% and 93.8% of C1-M27 and C2 in 2020, respectively, and the blaCTX-M possession in C1-nM27 increased from 19.2% in 2008-2009 to 40% in 2020. The FQ-resistant ST1193 was detected in 2020 only (17.9% of 151 isolates, of which 14.8% possessed blaCTX-M). CONCLUSION: The increased resistance of E. coli to FQ and third-generation cephalosporins in Japan can be attributed to the accumulation of blaCTX-M in C1-nM27 and the increase of C1-nM27 and C2 clades with high blaCTX-M possession, alongside spread of ST1193.
• 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, ［査読有り］, ［筆頭著者, 責任著者］, ［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.
• Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection.
  Tasuku Mariya; Toyotaka Sato; Yuya Fujibe; Manami Ishido; Hiroshi Shimada; Terufumi Kubo; Yoko Nagai; Wataru Arai; Suguru E Tanaka; Kyota Ashikawa; Yoshiyuki Sakuraba; Shinichi Ishioka; Shin-Ichi Yokota; Tsuyoshi Saito
  Medical molecular morphology, 54, 4, 374, 379, 2021年07月21日, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.
• Interleukin-27 promotes autophagy in human serum-induced primary macrophages via an mTOR- and LC3-independent pathway.
  Sylvain Laverdure; Ziqiu Wang; Jun Yang; Takuya Yamamoto; Tima Thomas; Toyotaka Sato; Kunio Nagashima; Tomozumi Imamichi
  Scientific reports, 11, 1, 14898, 14898, 2021年07月21日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner.
• 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, ［査読有り］, ［筆頭著者, 責任著者］, ［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.
• 治療上重要となる抗菌薬耐性に関する細菌学的解析
  佐藤豊孝; 佐藤豊孝
  日本細菌学雑誌(Web), 76, 3, 161, 174, 日本細菌学会, 2021年, ［査読有り］, ［筆頭著者, 責任著者］, ［国内誌］
  日本語, 細菌感染症における抗菌薬耐性の問題は医療現場にとって大きな問題である。特に現在の医療現場で使用頻度の高い第3世代セファロスポリン系抗菌薬やフルオロキノロン（FQ）系抗菌薬に対して，基質拡張型β-ラクタマーゼ産生（ESBL）およびFQ耐性大腸菌が我が国でも近年増加傾向である。一方で，多剤耐性菌への切り札や最終選択薬となるタゾバクタム－ピペラシリンやコリスチン，チゲサイクリンといった抗菌薬も医療上重要である。頻用性の高い抗菌薬耐性と比較すると耐性菌の分離率は低いながらもこれらに耐性を示す腸内細菌科細菌の報告がなされている。著者はこれまでに臨床現場から分離された細菌の薬剤耐性と多剤耐性化に関する研究を行ってきた。特に上記のような治療上重要となる抗菌薬耐性に関する細菌学的解析を札幌医科大学および札幌市内の医療施設の臨床検体から分離された大腸菌を中心に行なってきた。本稿ではこれまでに著者が得てきた知見を紹介させていただく。
• 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, ［査読有り］, ［筆頭著者, 責任著者］, ［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 (SMKP01mutSA307T) 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 SMKP01mutSA307T 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.
• Whole-Genome Sequence of Fluoroquinolone-Resistant Escherichia coli HUE1, Isolated in Hokkaido, Japan.
  Montgomery Munby; Jumpei Fujiki; Kotaro Aoki; Chika Kawaguchi; Keisuke Nakamura; Tomohiro Nakamura; Michihito Sasaki; Toyotaka Sato; Masaru Usui; Hirofumi Sawa; Shin-Ichi Yokota; Yutaka Tamura; Hidetomo Iwano
  Microbiology resource announcements, 9, 46, 2020年11月12日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, We report the complete genome sequence of Escherichia coli strain HUE1, isolated from the urinary catheter of a female patient, showing fluoroquinolone resistance without quinolone resistance-determining region mutations. To facilitate the exploration of the molecular characteristics of HUE1, the whole genome was sequenced using long- and short-read platforms.
• 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, ［査読有り］, ［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.
• 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08月04日, ［査読有り］, ［責任著者］, ［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.
• 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］, ［筆頭著者, 責任著者］, ［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.
• 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.
• 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］, ［責任著者］, ［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.
• Prevalence and characterization of Clostridioides difficile isolates from retail food products (vegetables and meats) in Japan.
  Masaru Usui; Aika Maruko; Michiko Harada; Fumi Kawabata; Tsubasa Sudo; Sayo Noto; Toyotaka Sato; Masaaki Shinagawa; Satoshi Takahashi; Yutaka Tamura
  Anaerobe, 61, 102132, 102132, 2020年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The present study aimed to elucidate the prevalence of Clostridioides difficile in Japanese retail food products. For this purpose, retail food samples (242 fresh vegetables and 266 retail meat samples: 89 chicken meat; 28 chicken liver; 200 pork meat; 24 pig liver; 127 beef meat) were collected from 14 supermarkets between 2015 and 2019. C. difficile was isolated from eight (3.3%) fresh vegetable, six (6.7%) chicken meat, one (3.6%) chicken liver, one (0.5%) pork meat, and two (1.6%) beef meat samples; it was not isolated from pig liver. Of these isolates, 35% were toxigenic. All isolates were typable by PCR ribotyping and were resolved into 12 PCR ribotypes. Among these isolates, ribotype 014, which is distributed worldwide including in Japanese clinical cases, was detected among vegetable isolates. Therefore, although the C. difficile contamination rate in Japanese retail foods was low, these sources can be contaminated and could transmit these bacteria to humans.
• 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］, ［責任著者］, ［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.
• Clonality investigation of clinical Escherichia coli isolates by polymerase chain reaction-based open-reading frame typing method.
  Masachika Saeki; Toyotaka Sato; Daisuke Furuya; Yuki Yakuwa; Yuki Sato; Ryo Kobayashi; Mayumi Ono; Shinya Nirasawa; Makito Tanaka; Hirotaka Nakafuri; Mami Nakae; Masaaki Shinagawa; Kouichi Asanuma; Nozomi Yanagihara; Shin-Ichi Yokota; Satoshi Takahashi
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26, 1, 38, 42, 2020年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Escherichia coli (E. coli) causes urinary tract infections, pneumonia, surgical site infections, and bloodstream infections and is the important pathogen for both community-acquired and healthcare-associated infections. To investigate the clonality of E. coli is important for infection control and prevention. We aimed to investigate the clonality of clinical E. coli isolates using Cica Geneus E. coli polymerase chain reaction (PCR)-based open-reading frame typing (POT) KIT and clarify the clinical usefulness of this kit. About 124 E. coli isolates obtained from inpatients at Sapporo Medical University Hospital were used. The POT method was used to classify 124 clinical isolates into 87 POT numbers. In addition to the clonality, it was possible to obtain additional information that 20 of the 124 isolates were extended-spectrum β-lactamase (ESBL) producing E. coli (5 isolates of CTX-M-1 group and 15 isolates of CTX-M-9 group) and 13 were sequence type (ST) 131 clone. Furthermore, when these ESBL-producing 20 isolates were compared with pulsed-field gel electrophoresis (PFGE) or multilocus sequence typing (MLST), Simpson's index of diversity was 0.968 in POT method, 0.979 in PFGE, and 0.584 in MLST. POT method had an analytical power similar to that of PFGE. In conclusion, attention should be paid to the difference in the interpretation of the results between the POT method and the PFGE, but POT method may be useful to timely monitor the spread of E. coli in medical facilities.
• Synthesis and biological evaluation of a MraY selective analogue of tunicamycins.
  Kazuki Yamamoto; Toyotaka Sato; Yuta Hikiji; Akira Katsuyama; Takanori Matsumaru; Fumika Yakushiji; Shin-Ichi Yokota; Satoshi Ichikawa
  Nucleosides, nucleotides & nucleic acids, 39, 1-3, 1, 16, 2019年09月30日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described.
• 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.
• Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in mcr-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-H30Rx and Non-x.
  Toyotaka Sato; Tsukasa Shiraishi; Yoshiki Hiyama; Hiroyuki Honda; Masaaki Shinagawa; Masaru Usui; Koji Kuronuma; Naoya Masumori; Satoshi Takahashi; Yutaka Tamura; Shin-Ichi Yokota
  Antimicrobial agents and chemotherapy, 62, 9, pii: AAC.00864-18, 2018年09月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (mcr) gene-negative colistin-resistant Escherichia coli clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-H30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter). In this study, we investigated the colistin resistance mechanism and identified novel amino acid substitutions or deletions in the PmrAB two-component system that activates eptA (encoding a phosphoethanolamine transferase) and arnT (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates. SRE34 possessed deletion Δ27-45 (LISVFWLWHESTEQIQLFE) in PmrB, SRE44 possessed substitution L105P in PmrA, and both SME222 and SME296 included substitution G206D in PmrB. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that lipid A is modified with phosphoethanolamine in all four isolates. Deletion of pmrAB decreased colistin MICs to 0.5 mg/liter and lowered eptA and arnT expression. Chromosomal replacement of mutated pmrA or pmrB in colistin-susceptible O25b:H4-ST131 strain SME98 (colistin MIC = 0.5 mg/liter) increased the colistin MIC to that of the respective parent colistin-resistant isolate. In addition, SME98 mutants in which pmrAB was replaced with mutated pmrAB showed no significant differences in bacterial growth and competition culture from the parent strain, except for the mutant with L105P in PmrA, whose growth was significantly suppressed in the presence of the parent strain. In conclusion, some O25b:H4-ST131 strains appear to acquire colistin resistance via phosphoethanolamine modification of lipid A through amino acid changes in PmrAB, and the amino acid changes in PmrB do not influence bacterial growth.
• Multiclonal expansion and high prevalence of β-lactamase-negative high-level ampicillin-resistant Haemophilus influenzae 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
  Antimicrob Agents Chemother., 62, 9, pii: AAC.00851-18, 2018年09月, ［査読有り］, ［責任著者］, ［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.
• Response to pneumococcal vaccine in interstitial lung disease patients: Influence of systemic immunosuppressive treatment.
  Koji Kuronuma; Hiroyuki Honda; Tessei Mikami; Atsushi Saito; Kimiyuki Ikeda; Mitsuo Otsuka; Hirofumi Chiba; Gen Yamada; Toyotaka Sato; Shin-Ichi Yokota; Hiroki Takahashi
  Vaccine, 36, 33, 4968, 4972, 2018年08月09日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.
• 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.
• Tigecycline Susceptibility of Klebsiella pneumoniae Complex and Escherichia coli Isolates from Companion Animals: The Prevalence of Tigecycline-Nonsusceptible K. pneumoniae Complex, Including Internationally Expanding Human Pathogenic Lineages.
  Sato T; Harada K; Usui M; Tsuyuki Y; Shiraishi T; Tamura Y; Yokota SI
  Microb Drug Resist., 24, 6, 860, 867, 2018年07月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Isolation of a mcr-1-harbouring Escherichia coli isolate from a human clinical setting in Sapporo, Japan.
  Toyotaka Sato; Akira Fukuda; Masaru Usui; Masaaki Shinagawa; Tsukasa Shiraishi; Yutaka Tamura; Satoshi Takahashi; Shin-Ichi Yokota
  Journal of global antimicrobial resistance, 13, 20, 21, 2018年06月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin.
  Shin-Ichi Yokota; Hiroshi Hakamada; Soh Yamamoto; Toyotaka Sato; Tsukasa Shiraishi; Masaaki Shinagawa; Satoshi Takahashi
  International journal of antimicrobial agents, 51, 6, 888, 896, 2018年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Pseudomonas aeruginosa is an important etiological agent of opportunistic infections. Injectable colistin is available as a last-line treatment option for multidrug-resistant P. aeruginosa infections. When cells were inoculated at a high number, colistin-susceptible P. aeruginosa grew on agar medium containing colistin at a concentration 10-fold higher than the minimum inhibitory concentration without acquiring colistin resistance. This study examined the responsible mechanism for growth in the presence of a high concentration of colistin. Cell wash fluid derived from P. aeruginosa efficiently reduced colistin antimicrobial activity. This reduction was mediated by lipopolysaccharide (LPS) in the wash fluid. Extracellular LPS inhibited colistin activity more effectively than cell-bound LPS in fixed cells. Cell wash fluids from Escherichia coli and Acinetobacter baumannii also reduced colistin activity; however, they were less potent than those from P. aeruginosa. The amount of LPS in cell wash fluid from P. aeruginosa was approximately 10-fold higher than that in fluid from E. coli or A. baumannii. In conclusion, cell-free LPS derived from bacterial cells inhibited the antimicrobial activity of colistin, and this effect was greatest for P. aeruginosa. Thus, large amounts of broken and dead cells of P. aeruginosa at infection foci will reduce the effectiveness of colistin, even against cells that have not yet acquired resistance.
• Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.
  Keisuke Yamamoto; Noriko Ogasawara; Soh Yamamoto; Kenichi Takano; Tsukasa Shiraishi; Toyotaka Sato; Hiroyuki Tsutsumi; Tetsuo Himi; Shin-Ichi Yokota
  Microbiology and immunology, 62, 2, 90, 98, 2018年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.
• Lipoteichoic acids are embedded in cell walls during logarithmic phase, but exposed on membrane vesicles in Lactobacillus gasseri JCM 1131T
  T. Shiraishi; S. Yokota; Y. Sato; T. Ito; S. Fukiya; S. Yamamoto; T. Sato; A. Yokota
  Beneficial Microbes, 9, 4, 653, 662, Wageningen Academic Publishers, 2018年, ［査読有り］
  英語, 研究論文（学術雑誌）
• High prevalence of mcr-1, mcr-3 and mcr-5 in Escherichia coli derived from diseased pigs in Japan.
  Akira Fukuda; Toyotaka Sato; Masaaki Shinagawa; Satoshi Takahashi; Tetsuo Asai; Shin-Ichi Yokota; Masaru Usui; Yutaka Tamura
  International journal of antimicrobial agents, 51, 1, 163, 164, 2018年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Novel antimicrobial activities of a peptide derived from a Japanese soybean fermented food, Natto, against Streptococcus pneumoniae and Bacillus subtilis group strains.
  Manabu Kitagawa; Tsukasa Shiraishi; Soh Yamamoto; Ryosuke Kutomi; Yasuo Ohkoshi; Toyotaka Sato; Hideki Wakui; Hideaki Itoh; Atsushi Miyamoto; Shin-Ichi Yokota
  AMB Express, 7, 1, 127, 127, 2017年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, We recently isolated a tumoricidal peptide from Natto, a Japanese traditional fermented food. In the present study, antimicrobial activity of the Natto peptide was examined. The peptide consisted of 45 amino acid residues, and its structure was predicted to be rich in α-helix. It excreted antimicrobial activity only against Streptococcus pneumoniae and Bacillus subtilis group (B. subtilis, Bacillus pumilus, and Bacillus licheniformis). Lesser antimicrobial activity was observed for Streptococcus species other than S. pneumoniae. Hemolysate or hemin was required for the antimicrobial activity of the peptide. The Natto peptide damages the cell membrane of B. subtilis. On the other hand, chain morphology was induced in S. pneumoniae, which is naturally diplococcus, during the early phases of the Natto peptide treatment; following that the cells were rapidly lysed. This suggested that the Natto peptide displayed a novel narrow spectrum of bactericidal activity and inhibited cell separation during cell division of S. pneumoniae.
• 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, pii: e01239-17, 2017年11月02日, ［査読有り］, ［筆頭著者］, ［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.
• Mycoplasma bovis isolates from dairy calves in Japan have less susceptibility than a reference strain to all approved macrolides associated with a point mutation (G748A) combined with multiple species-specific nucleotide alterations in 23S rRNA.
  Toyotaka Sato; Hidetoshi Higuchi; Shin-Ichi Yokota; Yutaka Tamura
  Microbiology and immunology, 61, 6, 215, 224, 2017年06月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47phox.
  Bharatwaj Sowrirajan; Yoshiro Saito; Deepak Poudyal; Qian Chen; Hongyan Sui; Suk See DeRavin; Hiromi Imamichi; Toyotaka Sato; Douglas B Kuhns; Noriko Noguchi; Harry L Malech; H Clifford Lane; Tomozumi Imamichi
  Scientific reports, 7, 43441, 43441, 2017年02月27日, ［査読有り］, ［国際誌］
  英語, Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47phox, a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47phox upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.
• NIP-SNAP-1 and-2 mitochondrial proteins are maintained by heat shock protein 60
  Soh Yamamoto; Tomoya Okamoto; Noriko Ogasawara; Shin Hashimoto; Tsukasa Shiraishi; Toyotaka Sato; Keisuke Yamamoto; Hiroyuki Tsutsumi; Kenichi Takano; Testuo Himi; Hideaki Itoh; Shin-ichi Yokota
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 483, 3, 917, 922, 2017年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production.
  Yamamoto S; Ogasawara N; Yamamoto K; Uemura C; Takaya Y; Shiraishi T; Sato T; Hashimoto S; Tsutsumi H; Takano K; Himi T; Yokota SI
  Biochem Biophys Res Commun, 483, 3, 911, 916, 2017年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648
  Toyotaka Sato; Yuuki Suzuki; Tsukasa Shiraishi; Hiroyuki Honda; Masaaki Shinagawa; Soh Yamamoto; Noriko Ogasawara; Hiroki Takahashi; Satoshi Takahashi; Yutaka Tamura; Shin-ichi Yokota
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 61, 2, pii: e01654-16, 2017年02月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Mycoplasma bovis isolates from dairy calves in Japan have reduced susceptibility to all approved macrolides, resulting from a point mutation (G748A) combined with multiple species-specific nucleotide alterations in 23S rRNA.
  Sato T; Higuchi H; Yokota SI; Tamura Y
  Microbiol. Immunol., 61, 214, 225, 2017年, ［査読有り］, ［筆頭著者］
• Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates
  Yasuo Ohkoshi; Toyotaka Sato; Yuuki Suzuki; Soh Yamamoto; Tsukasa Shiraishi; Noriko Ogasawara; Shin-ichi Yokota
  BIOMED RESEARCH INTERNATIONAL, 2017, 5470241, 2017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
  Toyotaka Sato; Akira Fukuda; Yuuki Suzuki; Tsukasa Shiraishi; Hiroyuki Honda; Masaaki Shinagawa; Soh Yamamoto; Noriko Ogasawara; Masaru Usui; Hiroki Takahashi; Satoshi Takahashi; Yutaka Tamura; Shin-ichi Yokota
  EMERGING INFECTIOUS DISEASES, 22, 12, 2223, 2225, 2016年12月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Clarithromycin prevents human respiratory syncytial virus-induced airway epithelial responses by modulating activation of interferon regulatory factor-3
  Keisuke Yamamoto; Soh Yamamoto; Noriko Ogasawara; Kenichi Takano; Tsukasa Shiraishi; Toyotaka Sato; Ryo Miyata; Takuya Kakuki; Ryuta Kamekura; Takashi Kojima; Hiroyuki Tsutsumi; Tetsuo Himi; Shin-ichi Yokota
  PHARMACOLOGICAL RESEARCH, 111, 804, 814, 2016年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production
  Shin Hashimoto; Soh Yamamoto; Noriko Ogasawara; Toyotaka Sato; Keisuke Yamamoto; Hiroshi Katoh; Toru Kubota; Tsukasa Shiraishi; Takashi Kojima; Tetsuo Himi; Hiroyuki Tsutsumi; Shin-ichi Yokota
  PLOS ONE, 11, 8, e0161793, 2016年08月, ［査読有り］
  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10月, ［査読有り］
• Isolation of Escherichia coli Strains with AcrAB-TolC Efflux Pump-Associated Intermediate Interpretation or Resistance to Fluoroquinolone, Chloramphenicol and Aminopenicillin from Dogs Admitted to a University Veterinary Hospital
  Toyotaka Sato; Shin-ichi Yokota; Risa Ichihashi; Tomoka Miyauchi; Torahiko Okubo; Masaru Usui; Nobuhiro Fujii; Yutaka Tamura
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 7, 937, 945, 2014年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Association of Veterinary Third-Generation Cephalosporin Use with the Risk of Emergence of Extended-Spectrum-Cephalosporin Resistance in Escherichia coli from Dairy Cattle in Japan
  Toyotaka Sato; Torahiko Okubo; Masaru Usui; Shin-ichi Yokota; Satoshi Izumiyama; Yutaka Tamura
  PLOS ONE, 9, 4, e96101, 2014年04月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Comparison of broad-spectrum cephalosporin-resistant Escherichia coli isolated from dogs and humans in Hokkaido, Japan
  Torahiko Okubo; Toyotaka Sato; Shin-ichi Yokota; Masaru Usui; Yutaka Tamura
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 20, 3-4, 243, 249, 2014年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Phylogenetic association of fluoroquinolone and cephalosporin resistance of D-O1-ST648 Escherichia coli carrying bla(CMY-2) from faecal samples of dogs in Japan
  Toyotaka Sato; Shin-ichi Yokota; Torahiko Okubo; Masaru Usui; Nobuhiro Fujii; Yutaka Tamura
  JOURNAL OF MEDICAL MICROBIOLOGY, 63, Pt2, 263, 270, 2014年02月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• The role of flies in spreading the extended-spectrum β-lactamase gene from cattle
  Usui M; Iwasa T; Fukuda A; Sato T; Okubo T; Tamura Y
  Microb Drug Resist., 19, 5, 415, 420, 2013年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• High Prevalence of Cross-Resistance to Aminoglycosides in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates
  Naoyuki Tsukamoto; Yasuo Ohkoshi; Torahiko Okubo; Toyotaka Sato; Osamu Kuwahara; Nobuhiro Fujii; Yutaka Tamura; Shin-ichi Yokot
  CHEMOTHERAPY, 59, 5, 379, 384, 2013年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Fluoroquinolone resistance mechanisms in an Escherichia coli isolate, HUE1, without quinolone resistance-determining region mutations
  Toyotaka Sato; Shin-Ichi Yokota; Ikuo Uchida; Torahiko Okubo; Masaru Usui; Masahiro Kusumoto; Masato Akiba; Nobuhiro Fujii; Yutaka Tamura
  Frontiers in Microbiology, 4, MAY, Frontiers Research Foundation, 2013年, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Amino acid substitutions in gyrA and parC are associated with fluoroquinolone resistance in mycoplasma bovis isolates from Japanese dairy calves
  Toyotaka Sato; Torahiko Okubo; Masaru Usui; Hidetoshi Higuchi; Yutaka Tamura
  Journal of Veterinary Medical Science, 75, 8, 1063, 1065, 2013年, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Contribution of the AcrAB-TolC efflux pump to high-level fluoroquinolone resistance in Escherichia coli isolated from dogs and humans
  Toyotaka Sato; Shin-Ichi Yokota; Torahiko Okubo; Kanako Ishihara; Hiroshi Ueno; Yasukazu Muramatsu; Nobuhiro Fujii; Yutaka Tamura
  Journal of Veterinary Medical Science, 75, 4, 407, 414, 2013年, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Prevalence of Fluoroquinolone-Resistant Escherichia coli O25:H4-ST131 (CTX-M-15-Nonproducing) Strains Isolated in Japan
  Shin-ichi Yokota; Toyotaka Sato; Torahiko Okubo; Yasuo Ohkoshi; Tamaki Okabayashi; Osamu Kuwahara; Yutaka Tamura; Nobuhiro Fujii
  CHEMOTHERAPY, 58, 1, 52, 59, 2012年, ［査読有り］
  英語, 研究論文（学術雑誌）
• A Fluoroquinolone-Resistant Escherichia coli Clinical Isolate without Quinolone Resistance-Determining Region Mutations Found in Japan
  Toyotaka Sato; Shin-ichi Yokota; Ikuo Uchida; Torahiko Okubo; Kanako Ishihara; Nobuhiro Fujii; Yutaka Tamura
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55, 8, 3964, 3965, 2011年08月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）

• 「さらなる感染症対策の高みへ向けて さまざまな視点からのアプローチ」人獣共通感染症における現状とその感染対策
  佐藤 豊孝, 日本臨床微生物学会雑誌, 36, Suppl.1, 241, 241, 2025年12月
  (一社)日本臨床微生物学会, 日本語
• 初代培養神経細胞およびアストロサイトにおけるプリオン増殖機序の解明
  鈴木 章夫; エルデネバト テムーレン; 上森 望未; 田中 美咲; 佐藤 豊孝; 堀内 基広, 日本獣医学会学術集会講演要旨集, 168回, 231, 231, 2025年09月
  (公社)日本獣医学会, 日本語
• 獣医学分野からのOne Healthアプローチ:AMR対策の現状と課題 我が国における伴侶動物由来耐性菌とOne Healthの動向
  佐藤 豊孝, 日本獣医学会学術集会講演要旨集, 168回, 256, 256, 2025年09月
  (公社)日本獣医学会, 日本語
• 伴侶動物由来Klebsiella pneumoniaeの薬剤感受性と分子疫学的解析
  佐藤 豊孝; Toyting Jirachaya; 遠山 茉奈; 露木 勇三; 鈴木 章夫; 堀内 基広, 日本獣医学会学術集会講演要旨集, 168回, 267, 267, 2025年09月
  (公社)日本獣医学会, 日本語
• 大腸菌ST131に対する新規ファージの分離とファージ耐性変異体の病原性の検証
  山本 晴香; 藤木 純平; 佐藤 豊孝; 岩野 英知, 日本獣医学会学術集会講演要旨集, 168回, 334, 334, 2025年09月
  (公社)日本獣医学会, 日本語
• 北海道大学における野生動物死因究明への取り組み
  直 亨則; 日尾野 隆大; 青島 圭佑; 市川 世識; 大谷 祐紀; 佐藤 豊孝; 池中 良徳; 松野 啓太; 堀内 基広, 日本獣医学会学術集会講演要旨集, 168回, 373, 373, 2025年09月
  (公社)日本獣医学会, 日本語
• One Healthに基づく札幌市およびその近郊から分離されたフルオロキノロン耐性大腸菌ST131の分子疫学的解析
  前田 愛子; 佐藤 豊孝; 大久保 寅彦; 福田 昭; Toyting Jirachaya; 臼井 優; 鈴木 章夫; 星野 佑治; 鳥越 慎吾; 榊原 啓一郎; 玉井 聡; 立花 徹; 堀内 基広, 北海道獣医師会雑誌, 69, 8, 372, 372, 2025年08月
  (公社)北海道獣医師会, 日本語
• 国内におけるカラスオルソレオウイルスによるカラス大量死事例
  市川 世識; 鈴木 玲海; Pau Valcorza; 後藤 拓磨; 古田 若葉; 日尾野 隆大; 直 亨則; 佐藤 豊孝; 池中 良徳; 石塚 真由美; 青島 圭佑; 木村 享史, 北海道獣医師会雑誌, 69, 8, 374, 374, 2025年08月
  (公社)北海道獣医師会, 日本語
• One Healthに基づく伴侶動物由来肺炎桿菌の薬剤感受性と分子疫学的解析
  佐藤 豊孝, 日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集, 99回・73回, O, 048, 2025年04月
  日本感染症学会・日本化学療法学会, 日本語
• 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, 2025年04月
  日本細菌学会, 英語
• イヌ腸管内での生存に重要なフルオロキノロン耐性大腸菌ST131遺伝子の同定
  前田 愛子; 佐藤 豊孝; 岡田 佳帆; 鈴木 章夫; 堀内 基広, 日本細菌学雑誌, 80, 2, 67, 67, 2025年04月
  日本細菌学会, 日本語
• One Healthに基づく伴侶動物由来緑膿菌の解析
  佐藤 豊孝, 日本化学療法学会雑誌, 73, 1, 56, 56, 2025年01月
  (公社)日本化学療法学会, 日本語
• One Healthに基づく薬剤耐性菌対策に資する研究
  佐藤豊孝, JATAFFジャーナル, 13, 2, 2025年
• One Healthに基づく伴侶動物由来緑膿菌の解析
  佐藤 豊孝, 日本化学療法学会雑誌, 73, 1, 56, 56, 2025年01月
  (公社)日本化学療法学会, 日本語
• 【抗菌薬を使いこなす～耐性菌を知る・防ぐ～】薬剤耐性菌の歴史と現状
  佐藤 豊孝, CAP: Companion Animal Practice, 39, 12, 16, 23, 2024年12月
  (株)緑書房, 日本語
• 【抗菌薬を使いこなす～耐性菌を知る・防ぐ～】薬剤耐性菌の歴史と現状
  佐藤 豊孝, CAP: Companion Animal Practice, 39, 12, 16, 23, 2024年12月
  (株)緑書房, 日本語
• 細菌学的解析手法を用いた薬剤耐性菌対策への新規アプローチ
  佐藤 豊孝, 日本細菌学雑誌, 79, 2, 27, 27, 2024年06月
  日本細菌学会, 日本語
• 北海道から細菌学を発信する 獣医学から薬剤耐性菌問題へのOne Health Approach
  前田 愛子; 佐藤 豊孝; 岡田 佳帆; 鈴木 章夫; 小松 勇介; 堀内 基広, 日本細菌学雑誌, 79, 2, 29, 29, 2024年06月
  日本細菌学会, 日本語
• 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, 2024年06月
  日本細菌学会, 英語
• 細菌学的解析手法を用いた薬剤耐性菌対策への新規アプローチ
  佐藤 豊孝, 日本細菌学雑誌, 79, 2, 27, 27, 2024年06月
  日本細菌学会, 日本語
• 北海道から細菌学を発信する 獣医学から薬剤耐性菌問題へのOne Health Approach
  前田 愛子; 佐藤 豊孝; 岡田 佳帆; 鈴木 章夫; 小松 勇介; 堀内 基広, 日本細菌学雑誌, 79, 2, 29, 29, 2024年06月
  日本細菌学会, 日本語
• フルオロキノロン耐性大腸菌ST131の市中伝播メカニズムの解析
  前田愛子; 佐藤豊孝; 前田愛子; 佐藤豊孝; 佐藤豊孝; 岡田佳帆; 鈴木章夫; 堀内基広; 鈴木章夫; 堀内基広; 堀内基広, 日本獣医学会学術集会講演要旨集, 167th, 247, 247, 2024年
  (公社)日本獣医学会, 日本語
• 新規抗菌薬開発を目指したMraY阻害剤ムレイドマイシン誘導体の創出研究
  淺尾健太; 山本一貴; 佐藤豊孝; 堀内基広; 市川聡, 日本蛋白質科学会年会(Web), 24th, 2024年
• 薬剤耐性菌感染症における感染部位特異的治療法の可能性評価
  佐藤 豊孝; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 72, 1, 114, 114, 2024年01月
  (公社)日本化学療法学会, 日本語
• 薬剤耐性菌におけるワンヘルス・アプローチ 伴侶動物由来の薬剤耐性菌について
  佐藤 豊孝, 日本臨床微生物学会雑誌, 34, Suppl.1, 150, 150, 2023年12月
  (一社)日本臨床微生物学会, 日本語
• 伴侶動物由来フルオロキノロン耐性大腸菌の特徴とヒトとの伝播の可能性の評価
  佐藤 豊孝; 上村 幸二朗; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 71, 4, 503, 503, 2023年07月
  (公社)日本化学療法学会, 日本語
• Candida albicansは尿糖の存在下で増殖促進に加えてアゾール系やフルシトシンの抗真菌薬の感受性が低下する
  桧山 佳樹; 佐藤 豊孝; 高橋 聡; 舛森 直哉; 横田 伸一, 日本化学療法学会雑誌, 71, 2, 175, 175, 2023年03月
  (公社)日本化学療法学会, 日本語
• Klebsiella pneumoniaeにおける遺伝子変異頻度と病原性の関連性評価
  上村 幸二朗; 佐藤 豊孝; 黒沼 幸治; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 71, 2, 179, 179, 2023年03月
  (公社)日本化学療法学会, 日本語
• 伴侶動物由来フルオロキノロン耐性大腸菌の特徴とヒトとの伝播の可能性の評価
  佐藤 豊孝; 上村 幸二朗; 高橋 聡; 横田 伸一, 日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集, 97回・71回, O, 294, 2023年03月
  日本感染症学会・日本化学療法学会, 日本語
• 抗菌性物質・薬剤耐性/生体防御 大腸菌ST131におけるmcr-1保有プラスミドの獲得による病原性減弱機構(Antimicrobial agents and resistance/Host defense Virulent attenuation mechanism by acquisition of mcr-1-harboring plasmid into Escherichia coli ST131)
  佐藤 豊孝; 山本 聡; 小笠原 徳子; 臼井 優; 長野 則之; 土井 洋平; 堀内 基広; 高橋 聡; 横田 伸一; 田村 豊, 日本細菌学雑誌, 78, 1, 48, 48, 2023年02月
  日本細菌学会, 英語
• プリオン感染マウスの中枢神経組織で見られる領域特異的な神経細胞死
  星加恭; 小松勇介; 小松勇介; TEMUULEN Erdenebat; 鈴木章夫; 佐藤豊孝; 佐藤豊孝; 堀内基広; 堀内基広, 日本Cell Death学会学術集会プログラム抄録集, 31st, 2023年
• マウス脳組織に存在するReal-time quaking-induced conversion法に対する阻害因子の同定とその除去法の応用
  鈴木章夫; 澤田和平; 中島拓; 小松勇介; 小松勇介; 佐藤豊孝; 佐藤豊孝; 堀内基広; 堀内基広, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023年
• プリオン感染マウスの中枢神経組織で観察される領域特異的な神経細胞死
  星加恭; 星加恭; 小松勇介; 小松勇介; ERDENEBAT Temuulen; ERDENEBAT Temuulen; 鈴木章夫; 佐藤豊孝; 佐藤豊孝; 堀内基広; 堀内基広, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023年
• 漢方薬における感染部位特異的抗菌活性の効能評価
  佐藤 豊孝, 上原記念生命科学財団研究報告集, 36, 1, 5, 2022年12月
  (公財)上原記念生命科学財団, 日本語
• 臨床検体由来フルオロキノロン耐性大腸菌の分子疫学解析および伴侶動物由来株との比較
  佐藤 豊孝; 上村 幸二朗; 高橋 聡; 横田 伸一, 日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集, 71回・69回, 133, 133, 2022年10月
  日本感染症学会東日本地方会・日本化学療法学会東日本支部, 日本語
• One Health Approachに基づいたフルオロキノロン耐性大腸菌の市中内拡散・定着様式の解明
  佐藤 豊孝; 立花 徹; 玉井 聡; 星野 祐治; 鳥越 慎吾; 榊原 啓一郎; 前谷 茂樹; 福田 昭; 大久保 寅彦; 臼井 優; 高橋 聡; 横田 伸一; 田村 豊; 堀内 基広, 日本獣医学会学術集会講演要旨集, 165回, [F2A, 10], 2022年09月
  (公社)日本獣医学会, 日本語
• 院内湿潤環境に対する注意喚起 北大附属動物病院における環境サーベイランス結果
  笹岡 一慶; 新田 優里香; 佐藤 豊孝; 堀内 基広; 滝口 満喜, 北海道獣医師会雑誌, 66, 8, 287, 287, 2022年08月
  (公社)北海道獣医師会, 日本語
• アメーバによる共生細菌依存的な細菌運搬現象のメカニズムの検証
  大久保 寅彦; 佐藤 豊孝; 横田 伸一; 中村 眞二; 山口 博之; 田中 菜那, 日本細菌学雑誌, 77, 1, 64, 64, 2022年02月
  日本細菌学会, 日本語
• アメーバによる共生細菌依存的な細菌運搬現象のメカニズムの検証
  大久保寅彦; 佐藤豊孝; 佐藤豊孝; 横田伸一; 中村眞二; 山口博之, 日本細菌学雑誌(Web), 77, 1, 2022年
• ジペプチドを用いたスキャニングによる新規ポリミキシン誘導体の創製研究
  家口凜太郎; 勝山彬; 勝山彬; 佐藤豊孝; 堀内基広; 横田伸一; 市川聡; 市川聡, 創薬懇話会講演要旨集, 2022, 2022年
• 多剤耐性大腸菌(HUE1)におけるファージ耐性化機構の解明
  市川奈津子; 藤木純平; 藤木純平; 川口千佳; MUNBY Montgomery; 中村圭佑; 中村暢宏; 中村暢宏; 中村暢宏; 佐藤豊孝; 岩野英知, 日本分子生物学会年会プログラム・要旨集(Web), 45th, 2022年
• 臨床検体由来フルオロキノロン耐性大腸菌の分子疫学解析および伴侶動物由来株との比較
  佐藤豊孝; 佐藤豊孝; 佐藤豊孝; 上村幸二朗; 高橋聡; 高橋聡; 横田伸一, 日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集, 71st-69th, 133, 133, 2022年
  日本感染症学会東日本地方会・日本化学療法学会東日本支部, 日本語
• プリオン感染動物の中枢神経組織における異なる神経細胞死機構の進行
  星加恭; 星加恭; 小松勇介; ERDENEBAT Temuulen; ERDENEBAT Temuulen; 鈴木章夫; 佐藤豊隆; 堀内基広, 日本分子生物学会年会プログラム・要旨集(Web), 45th, 2022年
• プリオン病の神経変性における“Regulated Cell Death”の関与に関する研究
  星加恭; 星加恭; 小松勇介; 鈴木章夫; 佐藤豊隆; 堀内基広, 日本獣医学会学術集会講演要旨集, 165th (CD-ROM), 2022年
• 人と動物の健康を守るワンヘルスの取組み-北海道大学One Healthリサーチセンターの活動紹介-
  堀内基広; 池中良徳; 山崎淳平; 佐藤豊孝; 鈴木章夫; 直亨則; 松野啓太; 澤洋文, 日本獣医師会獣医学術学会年次大会講演要旨集, 2022, 2022年
• 迅速ライブラリー構築とin situスクリーニングによるムレイドマイシンの構造活性相関研究
  淺尾健太; 山本一貴; 佐藤豊孝; 堀内基広; 横田伸一; 市川聡; 市川聡, 反応と合成の進歩シンポジウム講演要旨集, 48th, 2022年
• 多角的な視点から薬剤耐性菌を捉える 伴侶動物由来薬剤耐性菌のヒトに及ぼす影響
  佐藤 豊孝, 日本臨床微生物学会雑誌, 32, Suppl.1, 139, 139, 2021年12月
  (一社)日本臨床微生物学会, 日本語
• 血液培養液を用いたメチシリン耐性遺伝子検出試薬と培養法の結果が乖離した一例
  韮澤 慎也; 佐伯 理知; 佐藤 勇樹; 佐藤 豊孝; 高橋 聡, 日本臨床微生物学会雑誌, 32, Suppl.1, 253, 253, 2021年12月
  (一社)日本臨床微生物学会, 日本語
• 多角的な視点から薬剤耐性菌を捉える 伴侶動物由来薬剤耐性菌のヒトに及ぼす影響
  佐藤 豊孝, 日本臨床微生物学会雑誌, 32, Suppl.1, 139, 139, 2021年12月
  (一社)日本臨床微生物学会, 日本語
• 治療上重要となる抗菌薬耐性に関する細菌学的解析
  佐藤 豊孝, 日本細菌学雑誌, 76, 3, 161, 174, 2021年11月
  日本細菌学会, 日本語
• 共生細菌依存的にアメーバに起こる細菌運搬現象には運ばれる細菌のNa+/H+アンチポーターNhaAが関与する
  田中 菜那; 大久保 寅彦; 佐藤 豊孝; 横田 伸一; タパ・ジーワン; 山口 博之, 日本細菌学雑誌, 76, 1, 68, 68, 2021年02月
  日本細菌学会, 日本語
• Na+/H+アンチポーター(NhaA)は大腸菌の乾燥抵抗性を規定する
  榎枝秀朗; 田中菜那; 大久保寅彦; 佐藤豊孝; 横田伸一; THAPA Jeewan; 山口博之, 日本細菌学雑誌(Web), 76, 1, 2021年
• 共生細菌依存的にアメーバに起こる細菌運搬現象には運ばれる細菌のNa⁺/H⁺アンチポーターNhaAが関与する
  田中菜那; 大久保寅彦; 佐藤豊孝; 横田伸一; THAPA Jeewan; 山口博之, 日本細菌学雑誌(Web), 76, 1, 2021年
• FFPE胎盤検体を用いた16S rRNA次世代シークエンス解析による後方視的周産期侵襲性感染精査手法の提案
  真里谷奨; 佐藤豊孝; 藤部佑哉; 石堂茉泉; 嶋田浩志; 久保輝文; 長井陽子; 芦川享大; 桜庭喜行; 石岡伸一; 横田伸一; 齋藤豪, 日本臨床分子形態学会総会・学術集会講演プログラム・要旨集, 53rd, 2021年
• 抗緑膿菌活性を有するウリジルペプチド系天然物の構造活性相関研究
  寺澤侑馬; 佐高千里; 佐藤豊孝; 山本一貴; 勝山彬; 松丸尊紀; 松丸尊紀; 薬師寺文華; 横田伸一; 市川聡; 市川聡, 日本薬学会年会要旨集(Web), 141st, 2021年
• 環境からヒトの生活に侵入する病原微生物 家庭内One-Health 伴侶動物由来耐性菌と人臨床検体由来耐性菌の比較
  佐藤 豊孝; 高橋 聡; 横田 伸一; 田村 豊, 日本化学療法学会雑誌, 69, 1, 50, 50, 2021年01月
  (公社)日本化学療法学会, 日本語
• 生体内菌発育必須因子(vivoEF)を標的した血流感染症特異的vivoEF阻害薬の感染部位特異的抗菌活性効果の検討
  佐藤 豊孝; 臼井 優; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 69, 1, 90, 90, 2021年01月
  (公社)日本化学療法学会, 日本語
• Fosfomycinによる術前除菌が無効であった尿道損傷患者の尿から検出されたESBL産生大腸菌の細菌学的検討
  桧山 佳樹; 佐藤 豊孝; 高橋 聡; 舛森 直哉; 横田 伸一, 日本化学療法学会雑誌, 68, 3, 451, 451, 2020年05月
  (公社)日本化学療法学会, 日本語
• 院内感染 病院から病院外へ 病院外から病院へ 伴侶動物領域におけるESBL産生菌の現状
  佐藤 豊孝; 田村 豊; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 68, 2, 249, 250, 2020年03月
  (公社)日本化学療法学会, 日本語
• 伴侶動物領域におけるESBL産生菌の現状
  佐藤 豊孝; 田村 豊; 高橋 聡; 横田 伸一, 感染症学雑誌, 94, 2, 223, 223, 2020年03月
  (一社)日本感染症学会, 日本語
• 生体内菌発育必須因子(vivoEF)を標的とする感染部位特異的(ピンポイント)抗菌薬のスクリーニング
  佐藤 豊孝; 小笠原 徳子; 霧島 正浩; 高橋 聡; 横田 伸一, 感染症学雑誌, 94, 2, 248, 248, 2020年03月
  (一社)日本感染症学会, 日本語
• なるほど微生物学講座-不思議なミクロの世界- インフルエンザ菌におけるβ-ラクタムおよびキノロン系抗菌薬耐性に関する分子遺伝学的解析
  佐藤 豊孝; 本田 宏幸; 黒沼 幸治; 高橋 聡; 横田 伸一, 感染症学雑誌, 94, 臨増, 142, 142, 2020年03月
  (一社)日本感染症学会, 日本語
• プラスミド性コリスチン耐性菌はヒトの健康に対するハザードか? mcr保有プラスミドが大腸菌の性状に及ぼす影響とゲノム解析
  臼井 優; 福田 昭; 鈴木 仁人; 矢原 耕史; 川西 路子; 佐藤 豊孝; 横田 伸一; 高橋 聡; 浅井 鉄夫; 田村 豊, 感染症学雑誌, 94, 臨増, 232, 232, 2020年03月
  (一社)日本感染症学会, 日本語
• Haemophilus influenzaeのキノロン系抗菌薬耐性に関与する遺伝子変異の解析
  本田 宏幸; 佐藤 豊孝; 黒沼 幸治; 高橋 聡; 高橋 弘毅; 横田 伸一, 感染症学雑誌, 94, 臨増, 317, 317, 2020年03月
  (一社)日本感染症学会, 日本語
• Haemophilus influenzaeのキノロン系抗菌薬耐性に関与する遺伝子変異の解析
  本田宏幸; 本田宏幸; 佐藤豊孝; 黒沼幸治; 高橋聡; 高橋弘毅; 横田伸一, 感染症学雑誌, 94, 臨増, 317, 317, 2020年
  (一社)日本感染症学会, 日本語
• コリスチン耐性菌の定着性と治療効果に及ぼす影響
  佐藤豊孝; 小笠原徳子; 臼井優; 鈴木仁人; 長野則之; 土井洋平; 土井洋平; 田村豊; 高橋聡; 高橋聡; 横田伸一, 感染症学雑誌, 94, 臨増, 232, 233, 2020年
  (一社)日本感染症学会, 日本語
• フラグメント連結戦略を用いたポリミキシン類誘導体ライブラリーの簡便かつ迅速な構築
  家口凜太郎; 勝山彬; 佐藤豊孝; 横田伸一; 市川聡, 万有札幌シンポジウム, 32nd, 2020年
• ウリジルペプチド系天然物の構造活性相関研究
  寺澤侑馬; 佐高千里; 佐藤豊孝; 山本一貴; 勝山彬; 松丸尊紀; 松丸尊紀; 薬師寺文華; 横田伸一; 市川聡; 市川聡, 反応と合成の進歩シンポジウム講演要旨集, 2020年
• 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, 2020年01月
  日本細菌学会, 英語
• Campylobacter upsaliensisが検出された巨大肝嚢胞の1症例
  大越 康雄; 佐藤 豊孝; 村林 広美; 酒井 昂平; 横田 伸一, 日本臨床微生物学会雑誌, 30, Suppl.1, 308, 308, 2019年12月
  (一社)日本臨床微生物学会, 日本語
• 伴侶動物由来Klebsiella pneumoniae complexにおけるチゲサイクリン非感受性(Tigecycline-Nonsusceptible Klebsiella pneumoniae Complex Isolated from Companion Animals)
  佐藤 豊孝; 原田 和記; 横田 伸一, 日本細菌学雑誌, 74, 1, 102, 102, 2019年03月
  日本細菌学会, 英語
• 人臨床検体から分離された腸内細菌科細菌のコリスチン感受性および分子遺伝学的解析
  佐藤 豊孝; 品川 雅明; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 67, Suppl.A, 248, 248, 2019年03月
  (公社)日本化学療法学会, 日本語
• 侵襲性肺炎球菌感染症患者から分離された多剤耐性肺炎球菌の全ゲノム解析
  大越 康雄; 佐藤 豊孝; 村林 広美; 横田 伸一, 日本臨床微生物学会雑誌, 29, Suppl.1, 417, 417, 2018年12月
  (一社)日本臨床微生物学会, 日本語
• Lactobacillus gasseriに共通する種特異的なリポテイコ酸の化学構造
  白石 宗; 久富 亮佑; 佐藤 耶舞羽; 森田 直樹; 吹谷 智; 佐藤 豊孝; 横田 篤; 横田 伸一, エンドトキシン・自然免疫研究, 21, 35, 37, 2018年11月
  The lipoteichoic acid (LTA) is a specific polymer on Gram-positive bacterial cell surfaces, and is not found in Gram-negative bacterial cells. LTA is an amphipathic anionic polymer typically comprised of poly-glycerophosphate (GroP) linked to glycolipid of cell membrane. In general, hydroxyl groups of GroP residues in polymer region are often substituted by D-alanine and/or carbohydrates. Glycolipid anchor typically comprises diglycosylglycerolipid containing two acyl groups. On the other hand, structural variation on species-or strain-level has been observed in degree of polymerization, substitution ratio of the GroP repeating unit, and numbers of carbohydrate and acyl groups in glycolipid moiety. However, structural information has not sufficiently accumulated to discuss unity and diversity of LTA structures.
  
   We determined chemical structure of LTA derived from seven strains of Lactobacillus gasseri, an intestinal lactic acid bacterium. All strains shared common structure. Polymer chain comprised poly-GroP with partial substitution with D-alanine. Glycolipid anchor contained novel tetrasaccharide structure and two or three acyl groups. The three acyl group-containing glycolipid anchor is characteristic LTA structure in lactic acid bacteria, including Lactobacillus genus, Lactococcus genus and Leuconostoc genus. The tetrasaccharide structure has not been reported in other Gram-positive bacterial LTA. In conclusion, the tetrasaccharide-containing glycolipid anchor is unique and species-specific LTA structure in L. gasseri., 日本エンドトキシン・自然免疫研究会, 日本語
• 緑膿菌はリポ多糖の菌体外放出量が多く、高菌量下でコリスチンの抗菌活性が減弱する
  横田 伸一; 袴田 浩; 山本 聡; 佐藤 豊孝; 白石 宗, 緑膿菌感染症研究会講演記録, 52回, 52, 54, 2018年10月
  緑膿菌感染症研究会, 日本語
• 淋菌に対するpiperacillinとtazobactam/piperacillinの薬剤感受性の検討
  桧山 佳樹; 高橋 聡; 佐藤 豊孝; 山本 聡; 品川 雅明; 横田 伸一; 舛森 直哉, 日本性感染症学会誌, 29, 2, 236, 236, 2018年10月
  (一社)日本性感染症学会, 日本語
• 乳酸桿菌の対数期に膜小胞上に局在するリポテイコ酸
  白石 宗; 横田 伸一; 佐藤 耶舞羽; 伊藤 利章; 吹谷 智; 山本 聡; 佐藤 豊孝; 横田 篤, 日本乳酸菌学会誌, 29, 2, 116, 116, 2018年07月
  日本乳酸菌学会, 日本語
• 入院治療中にアミカシン耐性を獲得した多剤耐性Klebsiella pneumoniaeの全ゲノム解析
  佐藤 豊孝; 品川 雅明; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 66, Suppl.A, 252, 252, 2018年04月
  (公社)日本化学療法学会, 日本語
• 緑膿菌で汚染させた末端透析液および金属腐食ポンプに対する洗浄・消毒効果に関する検討
  中村 実; 横田 伸一; 白石 宗; 佐藤 豊孝; 木村 主幸; 岡山 雅哉; 小林 陽介; 柴田 晴昭; 萩原 誠也; 名和 伴恭, 日本臨床工学技士会会誌, 63, 142, 142, 2018年04月
  (公社)日本臨床工学技士会, 日本語
• 侵襲性肺炎球菌感染症患者から分離された多剤耐性肺炎球菌の解析
  本田 宏幸; 佐藤 豊孝; 大越 康雄; 村林 広美; 小林 智史; 齋藤 充史; 錦織 博貴; 黒沼 幸治; 高橋 弘毅; 横田 伸一, 日本化学療法学会雑誌, 66, Suppl.A, 289, 289, 2018年04月
  (公社)日本化学療法学会, 日本語
• 免疫抑制療法中の間質性肺疾患患者における肺炎球菌ワクチンの効果の検討
  黒沼 幸治; 本田 宏幸; 齋藤 充史; 小林 智史; 錦織 博貴; 佐藤 豊孝; 横田 伸一; 高橋 弘毅, 日本化学療法学会雑誌, 66, Suppl.A, 378, 378, 2018年04月
  (公社)日本化学療法学会, 日本語
• 種特異的な構造を有するLactobacillus gasseriリポテイコ酸のヒト腸管上皮細胞株でのIL-8産生への影響
  久富 亮佑; 白石 宗; 佐藤 豊孝; 横田 伸一, 日本細菌学雑誌, 73, 1, 89, 89, 2018年02月
  日本細菌学会, 日本語
• 大腸菌臨床分離株におけるepidemic clone ST131のコリスチンおよびチゲサイクリン耐性(Colistin and tigecycline resistance in an epidemic clone, ST131, Escherichia coli clinical isolates)
  佐藤 豊孝; 臼井 優; 品川 雅明; 福田 昭; 本田 宏幸; 白石 宗; 田村 豊; 高橋 聡; 横田 伸一, 日本細菌学雑誌, 73, 1, 146, 146, 2018年02月
  日本細菌学会, 英語
• β-lactamase-negative ampicillin-resistant Haemophilus influenzae臨床分離株の遺伝学的特徴
  本田 宏幸; 佐藤 豊孝; 高橋 弘毅; 横田 伸一, 日本細菌学雑誌, 73, 1, 147, 147, 2018年02月
  日本細菌学会, 日本語
• 緑膿菌はリポ多糖の菌体外放出量が多く,高菌量下でコリスチンの抗菌活性が減弱する。
  横田伸一; 袴田浩; 塚本尚行; 山本聡; 佐藤豊孝; 白石宗, 緑膿菌感染症研究会プログラム・抄録集, 52nd, 2018年
• β-lactamase-negative ampicillin-resistant Haemophilus influenzae臨床分離株の遺伝学的特徴
  本田宏幸; 本田宏幸; 佐藤豊孝; 高橋弘毅; 横田伸一, 日本細菌学雑誌(Web), 73, 1, 2018年
• 種特異的な構造を有するLactobacillus gasseriリポテイコ酸のヒト腸管上皮細胞株でのIL-8産生への影響
  久富亮佑; 白石宗; 佐藤豊孝; 横田伸一, 日本細菌学雑誌(Web), 73, 1, 2018年
• 納豆由来ペプチドの特異な殺菌効果とその作用機序
  白石 宗; 北川 学; 山本 聡; 久富 亮佑; 佐藤 豊孝; 涌井 秀樹; 伊藤 英晃; 宮本 篤; 横田 伸一, エンドトキシン・自然免疫研究, 20, 39, 42, 2017年10月
  日本エンドトキシン・自然免疫研究会, 日本語, 記事・総説・解説・論説等（その他）
• 連載 私達の研究(173) 抗菌薬多剤耐性におけるefflux pumpの役割を見直す
  横田伸一; 佐藤豊孝, 化学療法の領域, 33, 8, 150, 155, 2017年07月25日
  医薬ジャーナル社
• 私達の研究 抗菌薬多剤耐性におけるefflux pumpの役割を見直す
  横田 伸一; 佐藤 豊孝, 化学療法の領域, 33, 8, 1698, 1703, 2017年07月
  (株)医薬ジャーナル社, 日本語, 記事・総説・解説・論説等（学術雑誌）
• Lactobacillus gasseri種に共通する種特異的なリポテイコ酸の化学構造
  久富 亮佑; 白石 宗; 佐藤 耶舞羽; 森田 直樹; 吹谷 智; 佐藤 豊孝; 横田 篤; 横田 伸一, 日本乳酸菌学会誌, 28, 2, 123, 123, 2017年06月
  日本乳酸菌学会, 日本語
• Haemophilus influenzaeのキノロン系抗菌薬耐性獲得機序についての検討
  本田 宏幸; 佐藤 豊孝; 高橋 弘毅; 横田 伸一, 感染症学雑誌, 91, 臨増, 376, 376, 2017年03月
  (一社)日本感染症学会, 日本語
• マクロライド作用機序 クラリスロマイシンの炎症反応修飾作用の分子機構の解明 気道上皮細胞のクラリスロマイシン結合タンパク質の同定と機能解析
  横田 伸一; 山本 聡; 小笠原 徳子; 植村 知加; 高谷 芳明; 伊藤 英晃; 山本 圭佑; 白石 宗; 佐藤 豊孝; 氷見 徹夫, The Japanese Journal of Antibiotics, 70, Suppl.A, 60, 64, 2017年03月
  (公財)日本感染症医薬品協会, 日本語
• 大腸菌臨床分離株におけるフルオロキノロン系抗菌薬耐性とチゲサイクリン耐性との関連性
  佐藤 豊孝; 品川 雅明; 高橋 聡; 横田 伸一, 日本化学療法学会雑誌, 65, Suppl.A, 274, 274, 2017年03月
  (公社)日本化学療法学会, 日本語
• Lactobacillus gasseri種に共通するリポテイコ酸の特異的構造
  久富 亮佑; 白石 宗; 佐藤 耶舞羽; 森田 直樹; 吹谷 智; 佐藤 豊孝; 横田 篤; 横田 伸一, 日本細菌学雑誌, 72, 1, 86, 86, 2017年02月
  日本細菌学会, 日本語
• タゾバクタム/ピペラシリン耐性大腸菌の耐性機構の解析
  鈴木 裕樹; 佐藤 豊孝; 山本 聡; 小笠原 徳子; 白石 宗; 品川 雅明; 高橋 聡; 横田 伸一, 日本細菌学雑誌, 72, 1, 138, 138, 2017年02月
  日本細菌学会, 日本語
• 日本のダイズ発酵食品である納豆由来ペプチドの新規の抗菌活性(Novel antimicrobial activities of a peptide derived from a Japanese soy-bean fermented food, Natto)
  北川 学; 白石 宗; 山本 聡; 久富 亮佑; 佐藤 豊孝; 小笠原 徳子; 宮本 篤; 横田 伸一, 日本細菌学雑誌, 72, 1, 145, 145, 2017年02月
  日本細菌学会, 日本語
• Haemophilus influenzaeのキノロン系抗菌薬耐性獲得機序についての検討
  本田宏幸; 佐藤豊孝; 高橋弘毅; 横田伸一, 日本化学療法学会雑誌, 65, Supplement-A, 2017年
• 日本の大豆発酵食品,納豆から抽出されたペプチドの新規殺菌作用
  北川学; 北川学; 白石宗; 山本聡; 久富亮佑; 佐藤豊孝; 小笠原徳子; 宮本篤; 横田伸一, 日本細菌学雑誌(Web), 72, 1, 2017年
• タゾバクタム/ピペラシリン耐性大腸菌の耐性機構の解析
  鈴木裕樹; 佐藤豊孝; 山本聡; 小笠原徳子; 白石宗; 品川雅明; 高橋聡; 高橋聡; 横田伸一, 日本細菌学雑誌(Web), 72, 1, 2017年
• Lactobacillus gasseri種に共通するリポテイコ酸の特異的構造
  久富亮佑; 白石宗; 佐藤耶舞羽; 森田直樹; 吹谷智; 佐藤豊孝; 横田篤; 横田伸一, 日本細菌学雑誌(Web), 72, 1, 2017年
• POTキット大腸菌用による分子疫学解析の検討
  佐伯 理知; 品川 雅明; 佐藤 豊孝; 八鍬 佑貴; 韮澤 慎也; 佐藤 勇樹; 高橋 聡, 日本臨床微生物学雑誌, 27, Suppl., 373, 373, 2016年12月
  (一社)日本臨床微生物学会, 日本語
• 日本における大腸菌のプラスミド性コリスチン耐性遺伝子(mcr-1)保有状況とヒト医療に与える影響
  福田 昭; 佐藤 豊孝; 鈴木 裕樹; 臼井 優; 浅井 鉄夫; 横田 伸一; 田村 豊, 日本獣医学会学術集会講演要旨集, 159回, 415, 415, 2016年08月
  (公社)日本獣医学会, 日本語
• 対数期におけるLactobacillus gasseri JCM1131^Tのリポテイコ酸の局在
  白石宗; 横田伸一; 佐藤耶舞羽; 伊藤利章; 吹谷智; 山本聡; 小笠原徳子; 佐藤豊孝; 横田篤, 日本農芸化学会大会講演要旨集(Web), 2016, 2016年
• 日本における子牛鼻腔内マイコプラズマ種の浸潤状況
  吉田 慎吾; 樋口 豪紀; 岩野 英知; 河合 一洋; 佐藤 豊孝; 田村 豊; 小岩 政照; 永幡 肇, 日本マイコプラズマ学会雑誌, 41, 34, 34, 2015年03月
  日本マイコプラズマ学会, 日本語
• 哺乳類HSP60の新規基質であるNIP-SNAP2タンパク質の機能
  山本聡; 小笠原徳子; 白石宗; 佐藤豊孝; 氷見徹夫; 伊藤英晃; 横田伸一, 臨床ストレス応答学会大会抄録集, 10th, 2015年
• 北海道で分離された大腸菌におけるキノロン、アミノグリコシド、セフェム交叉耐性株に関する検討
  横田 伸一; 大越 康雄; 大久保 寅彦; 佐藤 豊孝; 田村 豊; 塚本 尚行; 桑原 理, 日本化学療法学会雑誌, 62, Suppl.A, 403, 403, 2014年05月
  (公社)日本化学療法学会, 日本語
• 緑膿菌疫学マーカーの今昔 分子疫学的解析手法を用いた犬由来大腸菌におけるフルオロキノロン耐性およびセファロスポリン耐性の関連性
  佐藤 豊孝, 緑膿菌感染症研究会講演記録, 47回, 44, 46, 2013年12月
  分子疫学的解析手法を用いた犬由来大腸菌におけるフルオロキノロン耐性およびセファロスポリン耐性の関連性について検討した。患犬の直腸スワブから分離した大腸菌81株を用いた。フルオロキノロン(FQ)耐性を示す株(38株)は全てに(QRDR)内にアミノ酸置換を伴う変異を複数認めた。セファロスポリン(CEP)耐性を示す株(32株)では、blaCMY-2(18株)、blaCTX-M-14(4株)、blaCTM-M-27(1株)を保有していた。その他β-ラクタマーゼ遺伝子保有CEP耐性株は全てampC promoter region内にampCの過剰産生を伴う変異を保有していた。FQRECsとFQ-CEPRECs間に系統発生分類の分布に有意な相関が得られた。, 緑膿菌感染症研究会, 日本語
• 動物病院来院猫からのセファロスポリン耐性およびフルオロキノロン耐性大腸菌の検出
  大久保 寅彦; 小野 匡; 佐藤 豊孝; 臼井 優; 田村 豊, 北海道獣医師会雑誌, 57, 8, 411, 411, 2013年08月
  (公社)北海道獣医師会, 日本語
• 犬由来大腸菌におけるフルオロキノロン耐性及びセファロスポリン耐性の関連
  佐藤 豊孝; 横田 伸一; 大久保 寅彦; 臼井 優; 藤井 暢弘; 田村 豊, 日本獣医師会雑誌, 66, 5, 350, 350, 2013年05月
  (公社)日本獣医師会, 日本語
• 伴侶動物由来細菌へのフルオロキノロン剤曝露による耐性菌出現リスク
  臼井 優; 佐藤 豊孝; 大久保 寅彦; 田村 豊, 獣医畜産新報, 66, 4, 279, 282, 2013年04月
  文永堂出版(株), 日本語
• 分子疫学的解析手法を用いた犬由来大腸菌におけるフルオロキノロン耐性およびセファロスポリン耐性の関連性
  佐藤豊孝, 緑膿菌感染症研究会プログラム・抄録集, 47th, 2013年
• 北海道における子ウシ鼻腔内Mycoplasma種の浸潤調査
  樋口 豪紀; 岩野 英知; 河合 一洋; 榊原 優子; 佐藤 豊孝; 小岩 政照; 田村 豊; 永幡 肇, 北海道獣医師会雑誌, 56, 8, 390, 390, 2012年08月
  (公社)北海道獣医師会, 日本語
• 市販鶏肉由来薬剤耐性サルモネラ属菌における耐性遺伝子の解析
  小川 紋; 佐藤 豊孝; 大久保 寅彦; 臼井 優; 田村 豊, 北海道獣医師会雑誌, 56, 8, 436, 436, 2012年08月
  (公社)北海道獣医師会, 日本語
• 薬剤耐性大腸菌の畜舎内伝播におけるハエの役割
  臼井 優; 岩佐 友寛; 佐藤 豊孝; 大久保 寅彦; 田村 豊, 北海道獣医師会雑誌, 56, 8, 437, 437, 2012年08月
  (公社)北海道獣医師会, 日本語
• 犬由来大腸菌におけるフルオロキノロン耐性およびセファロスポリン耐性の関連
  佐藤 豊孝; 横田 伸一; 大久保 寅彦; 臼井 優; 藤井 暢弘; 田村 豊, 北海道獣医師会雑誌, 56, 8, 438, 438, 2012年08月
  (公社)北海道獣医師会, 日本語
• 牛呼吸器由来Mycoplasma bovisにおけるフルオロキノロン系抗菌薬耐性機構
  佐藤 豊孝; 大久保 寅彦; 臼井 優; 樋口 豪紀; 永幡 肇; 田村 豊, 日本獣医学会学術集会講演要旨集, 154回, 226, 226, 2012年08月
  (公社)日本獣医学会, 日本語
• 南極の氷中に含まれていた細菌叢の解析
  大久保 寅彦; 佐藤 豊孝; 中村 昇太; 飯田 哲也; 臼井 優; 能田 淳; 萩原 克郎; 田村 豊, 日本獣医学会学術集会講演要旨集, 154回, 229, 229, 2012年08月
  (公社)日本獣医学会, 日本語
• 薬剤耐性大腸菌の畜舎内伝播におけるハエの役割
  臼井 優; 岩佐 友寛; 佐藤 豊孝; 大久保 寅彦; 田村 豊, 日本獣医学会学術集会講演要旨集, 154回, 273, 273, 2012年08月
  (公社)日本獣医学会, 日本語
• 市販鶏肉由来薬剤耐性サルモネラ属菌における耐性遺伝子の解析
  小川 紋; 佐藤 豊孝; 大久保 寅彦; 臼井 優; 田村 豊, 日本獣医学会学術集会講演要旨集, 154回, 276, 276, 2012年08月
  (公社)日本獣医学会, 日本語
• イエネズミ糞便由来大腸菌の薬剤耐性調査
  吉沢 創太; 大久保 寅彦; 佐藤 豊孝; 臼井 優; 田中 和之; 石塚 真由美; 田村 豊, 北海道獣医師会雑誌, 56, 8, 437, 437, 2012年08月
  (公社)北海道獣医師会, 日本語
• イエネズミ糞便由来大腸菌の薬剤耐性調査
  吉沢 創太; 大久保 寅彦; 佐藤 豊孝; 臼井 優; 田中 和之; 石塚 真由美; 田村 豊, 日本獣医学会学術集会講演要旨集, 154回, 275, 275, 2012年08月
  (公社)日本獣医学会, 日本語
• 犬及び人由来フルオロキノロン耐性大腸菌におけるプラスミド介在性キノロン耐性遺伝子oqxABの検出
  佐藤 豊孝; 横田 伸一; 内田 郁夫; 大久保 寅彦; 石原 加奈子; 岡林 環樹; 藤井 暢弘; 田村 豊, 感染症学雑誌, 85, 5, 557, 557, 2011年09月
  (一社)日本感染症学会, 日本語
• マイコプラズマ性乳房炎の摘発を目的としたバルクスクリーニングの実施とその評価
  樋口 豪紀; 岩野 英知; 河合 一洋; 馬場 幸宏; 古岡 みゆき; 斉藤 哲; 佐藤 豊孝; 大林 哲; 小岩 政照; 横田 博; 田村 豊; 永幡 肇, 北海道獣医師会雑誌, 55, 8, 353, 353, 2011年08月
  (公社)北海道獣医師会, 日本語
• 犬および人由来フルオロキノロン耐性大腸菌の性状比較
  佐藤 豊孝; 横田 伸一; 大久保 寅彦; 石原 加奈子; 藤井 暢弘; 田村 豊, 北海道獣医師会雑誌, 55, 8, 417, 417, 2011年08月
  (公社)北海道獣医師会, 日本語
• ヒト及びイヌ由来大腸菌におけるプラスミド介在性キノロン耐性遺伝子aac(6')-Ib-crの検出
  北原 尚英; 佐藤 豊孝; 大久保 寅彦; 石原 加奈子; 田村 豊, 北海道獣医師会雑誌, 55, 8, 418, 418, 2011年08月
  (公社)北海道獣医師会, 日本語
• 牛における第三世代セファロスポリン使用による薬剤耐性菌の発生評価試験
  佐藤 豊孝; 大久保 寅彦; 石原 加奈子; 泉山 諭; 田村 豊, 日本獣医学会学術集会講演要旨集, 152回, 215, 215, 2011年08月
  (公社)日本獣医学会, 日本語
• 牛呼吸器由来マイコプラズマにおけるマクロライド系抗菌薬の薬剤感受性調査
  佐藤 豊孝; 樋口 豪紀; 大久保 寅彦; 石原 加奈子; 永幡 肇; 田村 豊, 日本獣医学会学術集会講演要旨集, 152回, 217, 217, 2011年08月
  (公社)日本獣医学会, 日本語
• ヒト及びイヌ由来大腸菌におけるプラスミド介在性キノロン耐性遺伝子aac(6')-Ib-crの検出
  北原 尚英; 佐藤 豊孝; 大久保 寅彦; 石原 加奈子; 田村 豊, 日本獣医学会学術集会講演要旨集, 152回, 262, 262, 2011年08月
  (公社)日本獣医学会, 日本語
• 犬及び人由来フルオロキノロン耐性大腸菌におけるプラスミド介在性キノロン耐性遺伝子oqxABの検出
  佐藤 豊孝; 横田 伸一; 内田 郁夫; 大久保 寅彦; 石原 加奈子; 岡林 環樹; 藤井 暢弘; 田村 豊, 感染症学雑誌, 85, 臨増, 191, 191, 2011年03月
  (一社)日本感染症学会, 日本語
• 犬および人から分離されたセファロスポリン耐性大腸菌における耐性性状の比較
  大久保 寅彦; 佐藤 豊孝; 石井 良和; 横田 伸一; 石原 加奈子; 田村 豊, 感染症学雑誌, 85, 臨増, 301, 301, 2011年03月
  (一社)日本感染症学会, 日本語
• 犬および人由来フルオロキノロン耐性大腸菌の性状比較
  佐藤 豊孝; 横田 伸一; 岡林 環樹; 石原 加奈子; 藤井 暢弘; 田村 豊, 感染症学雑誌, 84, 6, 821, 822, 2010年11月
  (一社)日本感染症学会, 日本語
• 犬由来フルオロキノロン-セファロスポリン多剤耐性大腸菌の系統発生分類による解析
  佐藤 豊孝; 横田 伸一; 大久保 寅彦; 石原 加奈子; 岡林 環樹; 藤井 暢弘; 田村 豊, 日本獣医学会学術集会講演要旨集, 150回, 253, 253, 2010年09月
  (公社)日本獣医学会, 日本語
• 犬および人由来セファロスポリン耐性大腸菌における耐性因子の比較
  大久保 寅彦; 佐藤 豊孝; 石原 加奈子; 石井 良和; 田村 豊, 日本獣医学会学術集会講演要旨集, 150回, 254, 254, 2010年09月
  (公社)日本獣医学会, 日本語
• 薬剤耐性 北海道で分離されたキノロン耐性大腸菌臨床分離株の分子疫学的解析
  横田 伸一; 佐藤 豊孝; 大越 康雄; 岡林 環樹; 田村 豊; 藤井 暢弘, 感染症学雑誌, 84, 臨増, 226, 227, 2010年03月
  (一社)日本感染症学会, 日本語
• 犬および人由来フルオロキノロン耐性大腸菌の性状比較
  佐藤 豊孝; 横田 伸一; 岡林 環樹; 石原 加奈子; 藤井 暢弘; 田村 豊, 感染症学雑誌, 84, 臨増, 436, 436, 2010年03月
  (一社)日本感染症学会, 日本語
• 犬由来大腸菌のフルオロキノロン耐性機構
  佐藤 豊孝; 石原 加奈子; 村松 康和; 上野 弘志; 岡林 環樹; 横田 伸一; 藤井 暢弘; 田村 豊, 日本獣医学会学術集会講演要旨集, 146回, 319, 319, 2008年09月
  (公社)日本獣医学会, 日本語
• 大容量PWRプラントの格納施設
  佐藤広栄; 音田豊孝, 火力発電, 23, 1, 1972年

• Antimicrobial resistance in respiratory pathogens in companion animals
  Toyotaka Sato
  U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) 25th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim, 2025年03月15日, 口頭発表（招待・特別）
  ［招待講演］
• Farm to table: the spread of antibiotic-resistant foodborne pathogens
  佐藤 豊孝
  Tokyo AMR One-Health Conference 2025, 2025年02月19日, 英語, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• 獣医学における感染症と耐性菌へのワンヘルスアプローチ
  佐藤 豊孝
  第一回日本危機管理医学会学術総会, 2025年02月15日, 日本語, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• Alternative Educational Tools to Enhance Learning on Responsible Antimicrobial Use in the Asia-Pacific Region
  Toyotaka Sato
  World Organisation for Animal Health (WOAH), 2025年02月06日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• 細菌学的解析手法を用いた薬剤耐性菌対策への新規アプローチ
  佐藤豊孝
  第97回日本細菌学会総会, 2024年08月07日, 口頭発表（招待・特別）
  ［招待講演］
• 機能性食品素材の薬剤耐性菌に対する抗菌効果の検証
  佐藤豊孝; 堀内基広
  統合医療機能性食品国際学会 第32回年会 （ICNIM 2024）, 2024年07月20日, 口頭発表（一般）
• 伴侶動物由来の薬剤耐性菌について
  佐藤 豊孝
  第35回日本臨床微生物学会総会・学術集会, 2024年02月10日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• DNA修復機構欠損変異株を用いた Klebsiella pneumoniaeの薬剤耐性および病原性進化予測
  佐藤 豊孝; 上村 幸二朗; 小笠原 徳子; 山本 聡; 齋藤 充; 黒沼 幸治; 堀内 基広; 髙橋 聡; 千葉 弘文; 横田 伸一
  第52回 薬剤耐性菌研究会, 2023年11月17日, 口頭発表（一般）
• 病原性細菌の加速度進化モデルを用いた未来予測
  佐藤 豊孝; 上村 幸二朗; 小笠原 徳子; 山本 聡; 齋藤 充史; 黒沼 幸治; 堀内 基広; 髙橋 聡; 千葉 弘文; 横田 伸一
  第 88 回 日本細菌学会北海道支部学術総会, 2023年08月26日, 口頭発表（一般）
• One Health Approachに基づく人と伴侶動物由来薬剤耐性菌の解析とその対策
  佐藤 豊孝
  第10回One World One Health 研究会, 2023年06月30日, 口頭発表（招待・特別）
  ［招待講演］
• 薬剤耐性菌の 国際的なトレンドを把握する
  佐藤 豊孝
  札幌医科大学附属病院 感染症医療教育・支援センター 主催 WEBセミナー, 2023年05月25日, 公開講演，セミナー，チュートリアル，講習，講義等
  ［招待講演］
• 伴侶動物由来フルオロキノロン耐性大腸菌の特徴とヒトとの伝播の可能性の評価
  佐藤 豊孝; 上村幸二郎; 髙橋 聡; 横田 伸一
  第97回日本感染症学会総会・学術講演会 第71回日本化学療法学会学術集会 合同学会, 2023年04月30日, 口頭発表（一般）
• Virulent attenuation mechanism by acquisition of mcr-1-harboring plasmid into Escherichia coli ST131
  佐藤豊孝; 山本聡; 小笠原徳子; 臼井優; 長野則之; 土井洋平; 堀内基広; 髙橋聡; 横田伸一; 田村豊
  第96回日本細菌学会総会, 2023年03月17日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• 薬剤耐性菌の克服に向けた感染部位特異的治療薬の開発
  佐藤 豊孝
  第18回 霊長類医科学フォーラム, 2022年11月22日, 英語, 口頭発表（招待・特別）
  ［招待講演］
• mcr-1保有プラスミドの付与が及ぼす大腸菌の病原性減弱メカニズムの解明
  佐藤豊孝; 山本聡; 小笠原徳子; 臼井優; 鈴木仁人; 林 航; 長野則之; 土井洋平; 田村豊; 髙橋聡; 横田伸一; 堀内基広
  第51回薬剤耐性菌研究会, 2022年11月12日, 日本語, 口頭発表（一般）
• Klebsiella pneumoniaeにおける遺伝子変異頻度と病原性の関連性評価
  上村幸二朗; 佐藤豊孝; 横田伸一
  第71回日本感染症学会東日本地方会学術集会・第69回日本化学療法学会東日本支部総会 合同学会, 2022年10月28日, 口頭発表（一般）
• 臨床検体由来フルオロキノロン耐性大腸菌の分子疫学解析および伴侶動物由来株との比較
  佐藤豊孝; 上村幸二郎; 髙橋 聡; 横田伸一
  第71回日本感染症学会東日本地方会学術集会・第69回日本化学療法学会東日本支部総会 合同学会, 2022年10月28日, 口頭発表（一般）
• 多剤耐性菌の克服に向けた新たなアプローチ 感染部位特異的細菌感染症治療法の開発
  佐藤 豊孝
  北海道大学 第8回部局横断シンポジウム 「新たな学際領域を生み出す異分野融合研究」, 2022年10月28日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• One Health Approachに基づいたフルオロキノロン耐性大腸菌の市中内拡散・定着様式の解明
  佐藤豊孝; 立花徹; 玉井聡; 星野祐治; 鳥越 慎吾; 榊原啓一郎; 前谷茂樹; 福田昭; 大久保寅彦; 臼井優; 髙橋聡; 横田伸一; 田村豊; 堀内基広
  第165回日本獣医学会学術集会, 2022年09月07日, 口頭発表（一般）
• 遺伝子修復機構欠損株を用いたKlebsiella pneumoniaeのheterogeneityが与える病原性と宿主内適応進化への影響評価
  上村幸二朗; 佐藤 豊孝; 小笠原徳子; 山本聡; 白石宗; 齋藤充史; 黒沼幸治; 堀内基広; 髙橋聡; 千葉弘文; 横田伸一
  第87回細菌北海道支部学術総会, 2022年08月27日, 口頭発表（一般）
• 従来の抗菌薬開発法にとらわれない、新たな細菌感染症治療薬のスクリーニングに関する研究開発
  佐藤豊孝
  第3回モダリティ創薬デザイン研究会シンポジウム～最先端のアカデミア研究がもたらす革新的モダリティ開発～, 2022年02月03日, シンポジウム・ワークショップパネル（指名）
  2022年02月03日 - 2022年02月03日, ［招待講演］
• 伴侶動物由来薬剤耐性菌のヒトに及ぼす影響
  佐藤 豊孝
  第33回日本臨床微生物学会総会・学術集会, 2022年01月29日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• 家庭内One-Health: 伴侶動物由来耐性菌と人臨床検体由来耐性菌の比較
  佐藤 豊孝、臼井 優、高橋 聡、横田 伸一
  第69回日本感染症学会東日本地方会学術集会・第67回日本化学療法学会東日本支部総会合同学会 シンポジウム11「環境からヒトの生活へ侵入する病原微生物」, 2020年10月22日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• コリスチン耐性菌の定着性と治療効果に及ぼす影響
  佐藤 豊孝
  第94回日本感染症学会学術講演会 シンポジウム 47 「プラスミド性コリスチン耐性菌はヒトの健康に対するハザードか？」, 2020年08月21日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• インフルエンザ菌におけるβ-ラクタムおよびキノロン系抗菌薬耐性に関する分子遺伝学的解析
  佐藤 豊孝
  第94回日本感染症学会学術講演会 シンポジウム 6 「なるほど微生物学講座-不思議なミクロの世界」, 2020年08月19日, シンポジウム・ワークショップパネル（指名）
  ［招待講演］
• 伴侶動物領域におけるESBL産生菌の現状
  佐藤 豊孝
  第68回日本感染症学会東日本地方会学術集会・第66回日本化学療法学会東日本支部総会合同学会 シンポジウム「院内感染 病院から病院外へ 病院外から病院へ」, 2019年10月18日, 日本語, シンポジウム・ワークショップパネル（指名）
  ［招待講演］, ［国内会議］
• 感染部位特異的細菌感染症治療法の確立に向けたvivoEF阻害剤の検索
  佐藤 豊孝
  BioJapan2019, 2019年10月11日, 日本語, 口頭発表（招待・特別）
• 既存抗菌薬の概念にとらわれない抗菌活性物質の検索とその評価
  佐藤 豊孝
  医薬品産業情報研究会, 2019年05月24日, 日本語, 口頭発表（招待・特別）
  ［招待講演］
• Molecular epidemiological analysis of antimicrobial drug-resistant Streptococcus penumoniae and Haemophilus influenzae isolated in Sapporo, in Japan.
  佐藤 豊孝
  U.S.-Japan Cooperative Medical Sciences Program (USJCMSP), 21st Acute Respiratory Infections (ARI) Panel Meeting – Bacterial Diseases, 2019年02月28日, 英語, 口頭発表（一般）
  ［招待講演］, ［国際会議］
• 医療で重要なペット由来薬剤耐性大腸菌の現状
  佐藤 豊孝
  第 8 回 日本医師会・日本獣医師会連携シンポジウム「家庭内ワンヘルスの取組み -人と動物における薬剤耐性(AMR)の実態と課題-」, 2018年11月15日, 日本語, シンポジウム・ワークショップパネル（指名）
  ［招待講演］, ［国内会議］
• Molecular epidemiological analysis of antimicrobial resistant bacteria isolated from animals and human.
  佐藤 豊孝
  The 7th bacteriology Special Seminar., 2018年08月10日, 英語, 口頭発表（招待・特別）
  ［招待講演］
• 基礎から見た臨床現場の耐性菌
  佐藤 豊孝
  第2回北海道微生物検査研究会, 2017年, 日本語, 口頭発表（招待・特別）
  ［招待講演］, ［国内会議］
• 人と動物から分離された薬剤耐性大腸菌の分子疫学的解析
  佐藤 豊孝
  札幌微生物研究者合同セミナー, 2015年, 日本語, 口頭発表（招待・特別）
  ［招待講演］

• 獣医衛生学特論, 2024年, 博士後期課程, 獣医学院
• 獣医衛生学特論, 2024年, 博士後期課程, 国際感染症学院
• 家畜育種学, 2024年, 学士課程, 獣医学部
• 動物衛生学実習, 2024年, 学士課程, 獣医学部
• 食品衛生学実習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部

• 2023年 - 現在
  薬剤耐性菌研究会
• 2023年 - 現在
  日本獣医師会
• 2024年
  動物用抗菌剤研究会
• 米国微生物学会
• 日本臨床微生物学会
• 日本化学療法学会
• 日本感染症学会
• 日本細菌学会
• 日本獣医学会

• ペプチドの迅速最適化プラットフォームの開発
  令和7年度 創薬基盤推進研究事業
  2025年04月 - 2030年03月
  市川 聡, 勝山 彬, 山本一貴, 佐藤 豊孝
  国立研究開発法人日本医療研究開発機構, 研究分担者
• 細菌のパンデミック成立様式解明への統合的アプローチ
  科学研究費助成事業
  2025年04月 - 2030年03月
  佐藤 豊孝
  日本学術振興会, 基盤研究(A), 研究代表者
• 非抗菌性物質を用いた細菌感染症治療薬に対する新規モダリティー創出技術の開発
  革新的先端研究開発支援事業 AMED-CREST
  2023年10月 - 2029年03月
  佐藤豊孝
  国立研究開発法人日本医療研究開発機構, ユニットタイプ「感染症創薬に向けた研究基盤の構築と新規モダリティ等の技術基盤の創出」研究開発領域, 国立大学法人 北海道大学 大学院獣医学研究院, 研究代表者
• パンデミッククローンST131をモデルとした大腸菌臨床株の乾燥抵抗性メカニズムの解明
  科学研究費助成事業
  2025年04月 - 2028年03月
  大久保 寅彦; 佐藤 豊孝; 山口 博之
  日本学術振興会, 基盤研究(C), 北海道大学, 研究分担者, 25K10357
• ワンヘルスアプローチによるモンゴルにおける食中毒起因菌と薬剤耐性菌の調査研究
  科学研究費助成事業
  2024年09月 - 2028年03月
  堀内 基広; 佐藤 豊孝; 笹岡 一慶
  日本学術振興会, 国際共同研究加速基金(海外連携研究), 北海道大学, ［国際共著］, 24KK0134
• 中分子天然物・天然物模倣ライブラリー構築支援と高機能化
  生命科学・創薬研究支援基盤事業(BINDS)
  2022年10月 - 2027年03月
  市川 聡; 勝山 彬; 山本一貴; 佐藤 豊孝
  国立研究開発法人日本医療研究開発機構(AMED), 研究分担者
• 進化学的トレードオフによる革新的ファージ療法の創出
  科学研究費助成事業
  2022年04月 - 2027年03月
  藤木 純平; 木下 真央; 佐藤 豊孝; 田村 昌大; 青木 弘太郎; 岩野 英知; 臼井 優; 権平 智; 酒井 俊和
  日本学術振興会, 基盤研究(B), 酪農学園大学, 研究分担者, 22H02526
• 病原性細菌の加速度進化モデルを用いた未来予測
  挑戦的研究(萌芽)
  2022年06月 - 2025年03月
  佐藤 豊孝
  日本学術振興会 科学研究費助成事業, 研究代表者
• 既存抗菌薬の副作用低減に必要な抗菌薬併用剤の最適化
  2022年度 武田科学振興財団 医学系研究助成 感染領域
  2022年09月 - 2024年03月
  佐藤 豊孝
  研究代表者
• 大腸菌バイオセンシングを応用した犬の消化器型リンパ腫の診断法の開発
  2022年度臨床研究推進研究
  2022年04月 - 2024年03月
  横山 望
  北海道大学動物医療センター, 研究分担者
• 小動物臨床における細菌性尿路感染症の迅速診断法の確立
  2022年度臨床研究推進研究
  2022年04月 - 2024年03月
  佐藤豊孝
  北海道大学動物医療センター, 研究代表者
• 「血流感染症特異的治療薬の開発に向けた大規模スクリーニングと vivoEF 阻害剤ライブラリーの構築」
  大学発新産業創出プログラム(START)「プロジェクト支援型」
  2021年11月 - 2024年03月
  佐藤 豊孝
  科学技術振興機 構(JST), 北海道大学獣医学研究院衛生分野獣医衛生学教室, 研究代表者
• 次世代の耐性菌対策を考慮した、国際的ハイリスク病原性細菌の市中内 定着様式の解明
  科学研究費助成事業 基盤研究(B)
  2021年04月 - 2024年03月
  佐藤 豊孝
  日本学術振興会, 研究代表者
• 低活性を示すToll様受容体アゴニストの情報伝達経路の解明
  科学研究費助成事業 基盤研究(B)
  2020年04月 - 2022年04月
  横田 伸一
  日本学術振興会, 研究分担者
• 家畜由来薬剤耐性菌の水圏・土壌環境を介した野菜汚染の定量評価及びヒトへの伝播に関する研究
  令和2年度食品健康影響評価技術研究
  2020年04月 - 2022年04月
  臼井 優
  内閣府食品安全委員会, 研究分担者
• 漢方薬における感染部位特異的抗菌活性の効能評価
  2020年度研究奨励
  2021年03月 - 2022年03月
  佐藤 豊孝
  上原記念生命科学財団, 研究代表者
• 従来の抗菌薬開発法にとらわれない、新たな細菌感染症治療薬のスクリーニングに関する研究開発
  令和元年度 「創薬基盤推進研究事業」
  2019年12月 - 2022年03月
  佐藤 豊孝
  国立研究開発法人日本医療研究開発機構(AMED), 研究代表者, 競争的資金
• 人に伝播し得る伴侶動物由来薬剤耐性菌の特性把握
  一般共同研究
  2020年04月 - 2021年03月
  佐藤 豊孝
  北海道大学人獣共通感染症リサーチセンター, 研究代表者
• 血液内における未知の生体内菌発育必須因子の同定および血流感染症特異的治療法の評価
  科学研究費助成事業 若手研究
  2019年04月 - 2021年03月
  佐藤 豊孝
  敗血症などの血流感染症は時に生命に関わる重篤な疾患であり、その多くが細菌感染症が原因とされる。本研究では、疾患敗血症などの血流感染症の成立に必要な病原菌の細菌因子の探索と同定を行い、複数の血液内での生存に必須な細菌因子を同定した。また、この細菌因子の働きを抑える化合物の同定にも成功した。
  日本学術振興会, 若手研究, 札幌医科大学, 研究代表者, 競争的資金, 19K16648
• ヒト小児咽頭扁桃における粘膜免疫誘導メカニズムの解明
  科学研究費助成事業 基盤研究(C)
  2018年04月 - 2021年03月
  小笠原 徳子; 山本 聡; 佐藤 豊孝
  小児期に最も発達を示す鼻咽腔粘膜関連リンパ組織(NALT)の構成成分であるヒト咽頭扁桃組織を用いて，ヒトNALTの機能解析を行うことを目的とした。初年度は1) ヒト咽頭扁桃組織、鼻腔洗浄液などを使用するために院内倫理委員会において本研究計画実施に関する倫理審査を受け、2) ヒト小児咽頭扁桃上皮細胞における検討の前に正常気道上皮細胞(NHBE)を購入し、NHBEによる単層培養および気液界面細胞培養系(Air-Liquid Interface: ALI)による気道上皮細胞の機能に関する予備検討を行なった。具体的には、RSウイルスやライのウイルスなどの呼吸器感染性ウイルス感染によるサイトカイン産生能力の誘導とサイトカイン産生誘導の阻害効果を持つ薬剤の気道上皮細胞における作用点の解析を行い、気道上皮細胞の果たす自然免疫の機能解析を行った。さらに3) フローサイトメトリ によるcell sortingを行うための細胞接着剥離に関する予備検討をNHBEを用いて行い、接着細胞剥離に使用できかつ細胞表面抗原の活性や発現を損なわない条件・薬剤を各種検討した。NHBEと咽頭扁桃上皮細胞の反応性に大きな違いがないかをウイルス感染に伴うサイトカイン産生能力や細胞間の接着を担うタイト結合タンパク質の局在を免疫染色で比較解析を試みNHBEと咽頭扁桃上皮細胞に大きな違いがないことを確認した。また粘膜免疫に関する知識を深めるためにThe 3rd international conference on innate lymphoid cell (2018年11月29日から12月1日、東京)に参加、鼻腔から得られた組織における2型自然リンパ球に関する研究結果をまとめposter 発表を行った。
  日本学術振興会, 基盤研究(C), 札幌医科大学, 18K09381
• 抗菌活性増強剤を用いた新規多剤耐性菌感染症治療法の検証
  令和２年度 創薬総合支援事業 (創薬ブースター)
  2020年04月
  佐藤 豊孝
  国立研究開発法人日本医療研究開発機構 (AMED), 研究代表者
• 伴侶動物およびヒト由来薬剤耐性菌の遺伝子学的類似性の検討
  一般共同研究
  2019年04月 - 2020年03月
  佐藤 豊孝
  北海道大学人獣共通感染症リサーチセンター, 研究代表者, 競争的資金
• The Young Ambassador Project Fund
  2019年02月 - 2019年12月
  佐藤 豊孝
  アメリカ微生物学会(ASM), 研究代表者, 競争的資金
• 多剤耐性菌感染症の克服に向けた、生体内菌発育必須因子の解析とその阻害剤の検索
  科学研究費助成事業 若手研究(B)
  2017年04月01日 - 2019年03月31日
  佐藤 豊孝
  本研究では、『試験管内では菌の生育・増殖には影響を与えないが、生体内(組織や血液内などの感染部位)において菌の発育・増殖に大きな影響を与える因子』を標的にし、これまでの新規抗菌性物質の検索手法(＝試験管内で菌体の発育・増殖を抑える化合物を検索)とは異なる視点で、今後より問題視される多剤耐性菌の制御に関する研究(本因子を阻害する化合物の検索、その阻害部位の同定、生体内での効果を明らかにする)を行った。その結果、血液内でのみ抗菌活性を示す化合物を複数同定し、その化合物が菌の莢膜の産生を抑えることを明らかとした。以上から、本研究で敗血症といった細菌性血流感染症の新たな治療法に関する科学的知見を得た。
  日本学術振興会, 若手研究(B), 札幌医科大学, 研究代表者, 競争的資金, 17K15688
• 薬剤耐性菌制圧に向けた天然物から創薬リードへの変換研究
  科学研究費助成事業 基盤研究(B)
  2016年04月01日 - 2019年03月31日
  市川 聡; 勝山 彬; 佐藤 豊孝
  １）ムライマイシンの制御型誘導体の合成を行った。２）スファエリミシン誘導体の合成とMraY阻害活性評価を行い、高いMraY阻害活性を有する誘導体を見出した。３）ムレイドマイシンA誘導体を合成し、高いMraY阻害活性と抗緑膿菌活性を有する誘導体を見出した。さらにMraYとの複合体のX線結晶構造解析を行った。４）プラスバシンA３誘導体の合成を行った。またプラスバシンA３の作用機構解析も行った。５）コリスチン耐性細菌に有効な誘導体を見出すべく、コリスチン誘導体30個を合成しその抗菌活性を評価した。本研究では、抗薬剤耐性菌薬リードを開発する事が出来たと言える。
  日本学術振興会, 基盤研究(B), 北海道大学, 16H05097
• 次世代シークエンサーを用いた、動物および人医療に潜む超低頻度薬剤耐性菌または未知の耐性獲得機構を持つ薬剤耐性菌の耐性機構の解明と分子疫学的解析
  一般共同研究
  2018年05月 - 2019年03月
  佐藤 豊孝
  北海道大学人獣共通感染症リサーチセンター, 研究代表者, 競争的資金
• コリスチン耐性菌の出現状況と特性解析に関する研究
  平成29年度食品健康影響評価技術研究
  2017年08月 - 2019年03月
  田村 豊
  内閣府食品安全委員会, 競争的資金
• 最先端次世代シークエンサーを用いた札幌医科大学附属病院から分離される薬剤耐性菌の耐性機構および分子疫学的解析
  特定医学研究推進事業・学術振興事業（教育研究事業）
  2017年07月 - 2018年03月
  佐藤 豊孝
  札幌医科大学, 研究代表者, 競争的資金
• リポ多糖による抗菌活性減弱を考慮した、多剤耐性緑膿菌感染症に対するコリスチンの適正使用に関する研究
  GSK Japan Research Grant 2016
  2016年11月 - 2017年04月
  佐藤 豊孝
  GSK グラクソ・スミスクライン株式会社, 研究代表者, 競争的資金
• インフルエンザ菌のフルオロキノロン低感受性に関わる分子疫学および分子遺伝学的解析
  科学研究費助成事業 研究活動スタート支援
  2015年08月28日 - 2017年03月31日
  佐藤 豊孝
  Haemophils influenzaeは気道常在菌であり，呼吸器感染症の起炎菌として知られる。 キノロン系抗菌薬は本菌に対する有効な治療薬である。キノロン耐性H.influenzaeの出現・拡大を阻止する上で、キノロン低感受性株の出現メカニズムの詳細な解析は重要であるが、明らかでない点が多い。本研究では、検査した全株がキノロン感受性であったが、64株中2株(3.1%)は感受性が低下しており、QRDR内にアミノ酸置換が認められた。キノロン誘導実験では55.2%がキノロン感受性の低下を起こし、34.4%がキノロン耐性を獲得した。またアンピシリン耐性とキノロン感受性低下に関連性が認められた。
  日本学術振興会, 研究活動スタート支援, 札幌医科大学, 15H06521
• 大腸菌臨床分離株における抗菌薬耐性の分子疫学的解析と耐性機構の解明
  研究助成
  2016年03月 - 2017年03月
  佐藤 豊孝
  湯浅記念会, 研究代表者, 競争的資金

• 抗菌剤のスクリーニング方法
  特許権, 佐藤 豊孝; 横田 伸一, 北海道公立大学法人 札幌医科大学
  特願2017-201889, 2017年10月18日
  特開2019-071853, 2019年05月16日
  特許第7515092号, 2024年07月04日
  202403012889979039

• 薬剤耐性菌、地球的脅威に 渡り鳥介し、南極のペンギンからも
  2024年07月
  本人以外
  毎日新聞
  ［新聞・雑誌］
• 抗生物質が効かない薬剤耐性菌 自然界に拡散
  2024年06月
  本人以外
  北海道新聞
  20面, ［新聞・雑誌］
• 薬剤耐性菌」人から自然環境に拡散か 早急な対策を 北大など
  2024年04月
  NHK
  ［テレビ・ラジオ番組］
• 抗生物質効かない薬剤耐性菌 人から自然環境に拡散の可能性
  2024年04月
  本人以外
  NHK北海道
  ［テレビ・ラジオ番組］
• 国際的啓発、学問発展に寄与
  2017年02月
  本人以外
  北海道医療新聞
  ４面, ［新聞・雑誌］
• 耐性菌生まない抗菌薬開発へ
  2017年02月
  本人以外
  北海道医療新聞
  ６面, ［新聞・雑誌］