Researcher basic information

• Ph.D. in Biological Science, Nara Institute of Science and Technology

• https://researchmap.jp/tomoe-kitao?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201701019825046937

• 201701019825046937

• 抗病原性ストラテジー
• タンパク質の機能・構造解析
• 病原性
• 細菌感染
• 薬剤耐性

• Life Science, Genome biology
• Life Science, Structural biochemistry
• Life Science, Molecular biology
• Life Science, Bacteriology

• Doctoral (PhD) degree program, Graduate School of Infectious Diseases

Research activity information

• 2019, 厚生労働省委託事業 第2回薬剤耐性あるある川柳, 佳作
  ペンネーム: T.K
• 2019, 日本細菌学会, 黒屋奨学賞
• Aug. 2017, 第11回細菌学若手コロッセウムinつくば, 優秀口頭発表賞
• Dec. 2015, BMB2015海外若手研究者招聘企画, Travel Grants for Early Career Researchers in Overseas
• Sep. 2015, 第2回バイオサイエンスグランプリ, 最優秀賞

• Legionella employs multimodal ubiquitination of Sec22b to modulate SNARE pairing
  Tomoe Kitao; Rina Iida; Hideki Kondo; Yoshiki Miura; Hikari Taka; Susan Kiiru; Toru Okamoto; Kohei Arasaki; Hideaki Higashi; Tomoko Kubori; Hiroki Nagai
  iScience, 29, 1, 1114341, Jan. 2026, [Peer-reviewed], [Lead author]
  English, Scientific journal
• EsxA, a type VII secretion system-dependent effector, reveals a novel function in the sporulation of Bacillus cereus ATCC14579
  Harvey K. Kamboyi; Atmika Paudel; Misheck Shawa; Misa Sugawara; Tuvshinzaya Zorigt; Joseph Y. Chizimu; Tomoe Kitao; Yoshikazu Furuta; Bernard M. Hang’ombe; Musso Munyeme; Hideaki Higashi
  BMC Microbiology, 24, 1, Springer Science and Business Media LLC, 17 Sep. 2024
  Scientific journal
• Multi-tiered actions of Legionella effectors to modulate host Rab10 dynamics
  Tomoko Kubori; Kohei Arasaki; Tomoe Kitao; Hiroki Nagai
  eLife Sciences Publications, Ltd, 08 Aug. 2023
  Rab GTPases are representative targets of manipulation by intracellular bacterial pathogens for hijacking membrane trafficking. Legionella pneumophila recruits many Rab GTPases to its vacuole and exploits their activities. Here, we found that infection-associated regulation of Rab10 dynamics involves ubiquitin signaling cascades mediated by the SidE and SidC families of Legionella ubiquitin ligases. Phosphoribosyl-ubiquitination of Rab10 catalyzed by the SidE ligases is crucial for its recruitment to the bacterial vacuole. SdcB, the previously uncharacterized SidC family effector, resides on the vacuole and contributes to retention of Rab10 at the late stages of infection. We further identified MavC as a negative regulator of SdcB. By the transglutaminase activity, MavC crosslinks ubiquitin to SdcB and suppresses its function, resulting in elimination of Rab10 from the vacuole. These results demonstrate that the orchestrated actions of many L. pneumophila effectors fine-tune the dynamics of Rab10 during infection.
• Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA
  Gus D. Warren; Tomoe Kitao; Tyler G. Franklin; Justine V. Nguyen; Paul P. Geurink; Tomoko Kubori; Hiroki Nagai; Jonathan N. Pruneda
  Molecular Cell, 83, 1, 105, 120.e5, Elsevier BV, Jan. 2023
  Scientific journal
• Synthetic engineering and biological containment of bacteriophages
  Shoichi Mitsunaka; Kohei Yamazaki; Ajeng K. Pramono; Megumi Ikeuchi; Tomoe Kitao; Naoya Ohara; Tomoko Kubori; Hiroki Nagai; Hiroki Ando
  Proceedings of the National Academy of Sciences, 119, 48, Proceedings of the National Academy of Sciences, 29 Nov. 2022
  Scientific journal, The serious threats posed by drug-resistant bacterial infections and recent developments in synthetic biology have fueled a growing interest in genetically engineered phages with therapeutic potential. To date, many investigations on engineered phages have been limited to proof of concept or fundamental studies using phages with relatively small genomes or commercially available “phage display kits”. Moreover, safeguards supporting efficient translation for practical use have not been implemented. Here, we developed a cell-free phage engineering and rebooting platform. We successfully assembled natural, designer, and chemically synthesized genomes and rebooted functional phages infecting gram-negative bacteria and acid-fast mycobacteria. Furthermore, we demonstrated the creation of biologically contained phages for the treatment of bacterial infections. These synthetic biocontained phages exhibited similar properties to those of a parent phage against lethal sepsis in vivo. This efficient, flexible, and rational approach will serve to accelerate phage biology studies and can be used for many practical applications, including phage therapy.
• Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
  Vijay K. Singh; Marianna Almpani; Damien Maura; Tomoe Kitao; Livia Ferrari; Stefano Fontana; Gabriella Bergamini; Elisa Calcaterra; Chiara Pignaffo; Michele Negri; Thays de Oliveira Pereira; Frances Skinner; Manos Gkikas; Danielle Andreotti; Antonio Felici; Eric Déziel; Francois Lépine; Laurence G. Rahme
  Nature Communications, 30 Aug. 2022
  Scientific journal
• Reversible modification of mitochondrial ADP/ATP translocases by paired Legionella effector proteins.
  Tomoko Kubori; Junyup Lee; Hyunmin Kim; Kohei Yamazaki; Masanari Nishikawa; Tomoe Kitao; Byung-Ha Oh; Hiroki Nagai
  Proceedings of the National Academy of Sciences of the United States of America, 119, 23, e2122872119, 07 Jun. 2022, [International Magazine]
  English, Scientific journal, SignificanceMitochondria are organelles of the central metabolism that produce ATP and play fundamental roles in eukaryotic cell function and thereby become targets for pathogenic bacteria to manipulate. We found that the intracellular bacterial pathogen, Legionella pneumophila, targets mitochondrial ADP/ATP translocases (ANTs), the function of which is linked to the mitochondrial ATP synthesis. This is achieved by a pair of effector proteins, Lpg0080 and Lpg0081, which have opposing enzymatic activities as an ADP ribosyltransferase (ART) and an ADP ribosylhydrolase (ARH), respectively, coordinately regulating the chemical modification of ANTs upon infection. Our structural analyses indicate that Lpg0081 is an ARH with a noncanonical macrodomain, whose folding topology is distinct from that of the canonical macrodomain of known eukaryotic, archaeal, and bacterial proteins.
• Requirement of phosphatidic acid binding for distribution of the bacterial protein Lpg1137 targeting syntaxin 17.
  Misaki Murata; Riku Kanamori; Tomoe Kitao; Tomoko Kubori; Hiroki Nagai; Mitsuo Tagaya; Kohei Arasaki
  Journal of cell science, 135, 6, 15 Mar. 2022, [International Magazine]
  English, Scientific journal, The gram-negative bacterium, Legionella pneumophila is known to manipulate the host cellular functions. L. pneumophila secretes bacterial proteins called Legionella effectors into the host cytosol that are necessary for these manipulations. The Legionella effector Lpg1137 was identified as a serine protease responsible for the degradation of syntaxin 17 (Stx17). However, how Lpg1137 specifically recognizes and degrades Stx17 remained unknown. Given that Stx17 is localized in the ER, mitochondria-associated membrane (MAM), and mitochondria, Lpg1137 likely distributes to these compartments to recognize Stx17. Here, we show that the C-terminal region of Lpg1137 binds to phosphatidic acid (PA), a MAM and mitochondria-enriched phospholipid, and that this binding is required for the correct intracellular distribution of Lpg1137. Two basic residues in the C-terminal region of Lpg1137 are required for PA binding and their mutation causes mislocalization of Lpg1137. This mutant also fails to degrade Stx17 while retaining protease activity. Taken together, our data reveal that Lpg1137 utilizes PA for its distribution to the membranous compartments in which Stx17 is localized.
• Recent advances in structural studies of the Legionella pneumophila Dot/Icm type IV secretion system.
  Tomoe Kitao; Tomoko Kubori; Hiroki Nagai
  Microbiology and immunology, 66, 2, 67, 74, Feb. 2022, [International Magazine]
  English, Scientific journal, The intracellular bacterial pathogen Legionella pneumophila utilizes the Dot/Icm type IV secretion system to translocate approximately 300 effector proteins to establish a replicative niche known as the Legionella-containing vacuole. The Dot/Icm system is classified as a type IVB secretion system, which is evolutionarily closely related to the I-type conjugation systems and is distinct from type IVA secretion systems, such as the Agrobacterium VirB/D4 system. Although both type IVA and IVB systems directly transport nucleic acids or proteins into the cytosol of recipient cells, the components and architecture of type IVB systems are much more complex than those of type IVA systems. Taking full advantage of rapidly developing cryo-electron microscopy techniques, the structural details of the transport apparatus and coupling complexes in the Dot/Icm system have been clarified in the past few years. In this review, we summarize recent progress in the structural studies of the L. pneumophila type IVB secretion system and the insights gained into the mechanisms of substrate recognition and transport.
• Protocol for imaging proteins associated with Legionella-containing vacuoles in host cells.
  Tomoe Kitao; Kohei Arasaki; Hiroki Nagai; Tomoko Kubori
  STAR protocols, 2, 2, 100410, 100410, 18 Jun. 2021, [International Magazine]
  English, Scientific journal, The intracellular bacterial pathogen Legionella pneumophila exploits host cellular systems using approximately 300 effector proteins to establish a replicative niche known as the Legionella-containing vacuole (LCV). During infection, both host and bacterial proteins interactively function on the LCVs. Here, we describe a detailed step-by-step protocol to visualize proteins associated with LCVs in host cells. This protocol can aid in analyzing whether a protein of interest influences the subcellular localization of LCV-associated proteins during infection. For complete details on the use and execution of this protocol, please refer to Kitao et al. (2020).
• Isolation and Characterization of a Novel Phage SaGU1 that Infects Staphylococcus aureus Clinical Isolates from Patients with Atopic Dermatitis.
  Yuzuki Shimamori; Ajeng K Pramono; Tomoe Kitao; Tohru Suzuki; Shin-Ichi Aizawa; Tomoko Kubori; Hiroki Nagai; Shigeki Takeda; Hiroki Ando
  Current microbiology, 78, 4, 1267, 1276, Apr. 2021, [International Magazine]
  English, Scientific journal, The bacterium Staphylococcus aureus, which colonizes healthy human skin, may cause diseases, such as atopic dermatitis (AD). Treatment for such AD cases involves antibiotic use; however, alternate treatments are preferred owing to the development of antimicrobial resistance. This study aimed to characterize the novel bacteriophage SaGU1 as a potential agent for phage therapy to treat S. aureus infections. SaGU1 that infects S. aureus strains previously isolated from the skin of patients with AD was screened from sewage samples in Gifu, Japan. Its genome was sequenced and analyzed using bioinformatics tools, and the morphology, lytic activity, stability, and host range of the phage were determined. The SaGU1 genome was 140,909 bp with an average GC content of 30.2%. The viral chromosome contained 225 putative protein-coding genes and four tRNA genes, carrying neither toxic nor antibiotic resistance genes. Electron microscopy analysis revealed that SaGU1 belongs to the Myoviridae family. Stability tests showed that SaGU1 was heat-stable under physiological and acidic conditions. Host range testing revealed that SaGU1 can infect a broad range of S. aureus clinical isolates present on the skin of AD patients, whereas it did not kill strains of Staphylococcus epidermidis, which are symbiotic resident bacteria on human skin. Hence, our data suggest that SaGU1 is a potential candidate for developing a phage therapy to treat AD caused by pathogenic S. aureus.
• Staphylococcal Phage in Combination with Staphylococcus Epidermidis as a Potential Treatment for Staphylococcus Aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants.
  Yuzuki Shimamori; Shoichi Mitsunaka; Hirotaka Yamashita; Tohru Suzuki; Tomoe Kitao; Tomoko Kubori; Hiroki Nagai; Shigeki Takeda; Hiroki Ando
  Viruses, 13, 1, 22 Dec. 2020, [International Magazine]
  English, Scientific journal, Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.
• Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase
  Tomoe Kitao; Kyoichiro Taguchi; Shintaro Seto; Kohei Arasaki; Hiroki Ando; Hiroki Nagai; Tomoko Kubori
  Cell Reports, 32, 10, 108107, 108107, Elsevier BV, Sep. 2020, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal, The intracellular bacterial pathogen Legionella pneumophila uses many effector proteins delivered by the bacterial type IV secretion system (T4SS) to hijack the early secretory pathway to establish its replicative niche, known as the Legionella-containing vacuole (LCV). On LCV biogenesis, the endoplasmic reticulum (ER) vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptors (v-SNARE) Sec22b is recruited to the bacterial phagosome and forms non-canonical pairings with target membrane SNAREs (t-SNAREs) from the plasma membrane. Here, we identify a Legionella deubiquitinase (DUB), LotB, that can modulate the early secretory pathway by interacting with coatomer protein complex I (COPI) vesicles when ectopically expressed. We show that Sec22b is ubiquitinated upon L. pneumophila infection in a T4SS-dependent manner and that, subsequently, LotB deconjugates K63-linked ubiquitins from Sec22b. The DUB activity of LotB stimulates dissociation of the t-SNARE syntaxin 3 (Stx3) from Sec22b, which resides on the LCV. Our study highlights a bacterial strategy manipulating the dynamics of infection-induced SNARE pairing using a bacterial DUB.
• Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination
  Tomoe Kitao; Hiroki Nagai; Tomoko Kubori
  Frontiers in Cellular and Infection Microbiology, 10, Frontiers Media SA, 21 Aug. 2020, [Peer-reviewed], [Lead author]
  English, Scientific journal
• Structural and Functional Analyses of the Legionella Virulence Secretion System
  Tomoe Kitao
  Seibutsu Butsuri, 2019
  Japanese, Scientific journal
• Molecular biological studies toward controlling infectious diseases caused by multidrug-resistant Pseudomonas aeruginosa.
  Kitao T
  Nihon saikingaku zasshi. Japanese journal of bacteriology, 74, 4, 177, 189, 2019, [Peer-reviewed]
  English, Scientific journal
• Emerging insights into bacterial deubiquitinases.
  Kubori T; Kitao T; Nagai H
  Current opinion in microbiology, 47, 14, 19, Nov. 2018, [Peer-reviewed]
  Scientific journal, Bacterial pathogens utilize eukaryotic cellular systems in various ways for their own benefits. To counteract host immune responses and survive in cells, bacteria modify host signaling pathways. For this aim, they have evolved virulence secretion systems. Bacteria-encoded effector proteins delivered via these secretion systems are the key players in bacterial pathogenesis. Ubiquitination is a post-translational modification that governs eukaryotic cellular systems. Recent studies have revealed that many bacterial effector proteins target the host ubiquitin system, often acting as ubiquitin-modulating enzymes such as ubiquitin ligases and deubiquitinases. Emerging lines of evidence have unveiled the diversity of bacterial deubiquitinases and have provided insights into the bacterial strategy to exploit the host ubiquitin system.
• LotA, a Legionella deubiquitinase, has dual catalytic activity and contributes to intracellular growth
  Tomoko Kubori; Tomoe Kitao; Hiroki Ando; Hiroki Nagai
  Cellular Microbiology, 20, 7, e12840, Blackwell Publishing Ltd, 01 Jul. 2018, [Peer-reviewed]
  English, Scientific journal
• Molecular Insights into Function and Competitive Inhibition of Pseudomonas aeruginosa Multiple Virulence Factor Regulator.
  Kitao T; Lepine F; Babloudi S; Walte F; Steinbacher S; Maskos K; Blaesse M; Negri M; Pucci M; Zahler B; Felici A; Rahme LG
  mBio, 9, 1, Jan. 2018, [Peer-reviewed]
  Scientific journal, New approaches to antimicrobial drug discovery are urgently needed to combat intractable infections caused by multidrug-resistant (MDR) bacteria. Multiple virulence factor regulator (MvfR or PqsR), a Pseudomonas aeruginosa quorum sensing transcription factor, regulates functions important in both acute and persistent infections. Recently identified non-ligand-based benzamine-benzimidazole (BB) inhibitors of MvfR suppress both acute and persistent P. aeruginosa infections in mice without perturbing bacterial growth. Here, we elucidate the crystal structure of the MvfR ligand binding domain (LBD) in complex with one potent BB inhibitor, M64. Structural analysis indicated that M64 binds, like native ligands, to the MvfR hydrophobic cavity. A hydrogen bond and pi interaction were found to be important for MvfR-M64 affinity. Surface plasmon resonance analysis demonstrated that M64 is a competitive inhibitor of MvfR. Moreover, a protein engineering approach revealed that Gln194 and Tyr258 are critical for the interaction between MvfR and M64. Random mutagenesis of the full-length MvfR protein identified a single-amino-acid substitution, I68F, at a DNA binding linker domain that confers M64 insensitivity. In the presence of M64, I68F but not the wild-type (WT) MvfR protein retained DNA binding ability. Our findings strongly suggest that M64 promotes conformational change at the DNA binding domain of MvfR and that the I68F mutation may compensate for this change, indicating allosteric inhibition. This work provides critical new insights into the molecular mechanism of MvfR function and inhibition that could aid in the optimization of anti-MvfR compounds and improve our understanding of MvfR regulation.IMPORTANCEPseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes serious acute, persistent, and relapsing infections. New approaches to antimicrobial drug discovery are urgently needed to combat intractable infections caused by this pathogen. The Pseudomonas aeruginosa quorum sensing transcription factor MvfR regulates functions important in both acute and persistent infections. We used recently identified inhibitors of MvfR to perform structural studies and reveal important insights that would benefit the optimization of anti-MvfR compounds. Altogether, the results reported here provide critical detailed mechanistic insights into the function of MvfR domains that may benefit the optimization of the chemical, pharmacological, and safety properties of MvfR antagonist series.
• Polypharmacology Approaches against the Pseudomonas aeruginosa MvfR Regulon and Their Application in Blocking Virulence and Antibiotic Tolerance
  Damien Maura; Steffen L. Drees; Arunava Bandyopadhaya; Tomoe Kitao; Michele Negri; Melissa Starkey; Biliana Lesic; Sylvain Milot; Eric Deziel; Robert Zahler; Mike Pucci; Antonio Felici; Susanne Fetzner; Francois Lepine; Laurence G. Rahme
  ACS CHEMICAL BIOLOGY, 12, 5, 1435, 1443, May 2017, [Peer-reviewed]
  English, Scientific journal
• Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection
  Dominique H. Limoli; Gregory B. Whitfield; Tomoe Kitao; Melissa L. Ivey; Michael R. Davis; Nora Grahl; Deborah A. Hogan; Laurence G. Rahme; P. Lynne Howell; George A. O'Toole; Joanna B. Goldberg
  MBIO, 8, 2, Mar. 2017, [Peer-reviewed]
  English, Scientific journal
• Evidence for Direct Control of Virulence and Defense Gene Circuits by the Pseudomonas aeruginosa Quorum Sensing Regulator, MvfR
  Damien Maura; Ronen Hazan; Tomoe Kitao; Alicia E. Ballok; Laurence G. Rahme
  SCIENTIFIC REPORTS, 6, 34083, Sep. 2016, [Peer-reviewed]
  English, Scientific journal
• Identification of Anti-virulence Compounds That Disrupt Quorum-Sensing Regulated Acute and Persistent Pathogenicity
  Melissa Starkey; Francois Lepine; Damien Maura; Arunava Bandyopadhaya; Biljana Lesic; Jianxin He; Tomoe Kitao; Valeria Righi; Sylvain Milot; Aria Tzika; Laurence Rahme
  PLOS PATHOGENS, 10, 8, e1004321, Aug. 2014, [Peer-reviewed]
  English, Scientific journal
• Development of an immunochromatographic assay for rapid detection of AAC(6 ')-Ib-producing Pseudomonas aeruginosa
  Tatsuya Tada; Tohru Miyoshi-Akiyama; Masashi Tanaka; Kenji Narahara; Masahiro Shimojima; Tomoe Kitao; Kayo Shimada; Teruo Kirikae
  JOURNAL OF MICROBIOLOGICAL METHODS, 91, 1, 114, 116, Oct. 2012, [Peer-reviewed]
  English, Scientific journal
• Emergence of a novel multidrug-resistant Pseudomonas aeruginosa strain producing IMP-type metallo-beta-lactamases and AAC(6 ')-Iae in Japan
  Tomoe Kitao; Tatsuya Tada; Masashi Tanaka; Kenji Narahara; Masahiro Shimojima; Kayo Shimada; Tohru Miyoshi-Akiyama; Teruo Kirikae
  INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 39, 6, 518, 521, Jun. 2012, [Peer-reviewed]
  English, Scientific journal
• Development of an immunochromatographic assay for diagnosing the production of IMP-type metallo-beta-lactamases that mediate carbapenem resistance in Pseudomonas
  Tomoe Kitao; Tohru Miyoshi-Akiyama; Masashi Tanaka; Kenji Narahara; Masahiro Shimojima; Teruo Kirikae
  JOURNAL OF MICROBIOLOGICAL METHODS, 87, 3, 330, 337, Dec. 2011, [Peer-reviewed]
  English, Scientific journal
• Complete Genome Sequence of Highly Multidrug-Resistant Pseudomonas aeruginosa NCGM2.S1, a Representative Strain of a Cluster Endemic to Japan
  Tohru Miyoshi-Akiyama; Tomoko Kuwahara; Tatsuya Tada; Tomoe Kitao; Teruo Kirikae
  JOURNAL OF BACTERIOLOGY, 193, 24, 7010, 7010, Dec. 2011, [Peer-reviewed]
  English, Scientific journal
• Genome Sequence of Multidrug-Resistant Pseudomonas aeruginosa NCGM1179
  Tatsuya Tada; Tomoe Kitao; Tohru Miyoshi-Akiyama; Teruo Kirikae
  JOURNAL OF BACTERIOLOGY, 193, 22, 6397, 6397, Nov. 2011, [Peer-reviewed]
  English, Scientific journal
• Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis
  Hiroki Ando; Tomoe Kitao; Tohru Miyoshi-Akiyama; Seiya Kato; Toru Mori; Teruo Kirikae
  MOLECULAR MICROBIOLOGY, 79, 6, 1615, 1628, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Development of an immunochromatographic assay for the rapid detection of AAC(6 ')-Iae-producing multidrug-resistant Pseudomonas aeruginosa
  Tomoe Kitao; Tohru Miyoshi-Akiyama; Kayo Shimada; Masashi Tanaka; Kenji Narahara; Nobuko Saito; Teruo Kirikae
  JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 65, 7, 1382, 1386, Jul. 2010, [Peer-reviewed]
  English, Scientific journal
• AAC(6 ')-Iaf, a Novel Aminoglycoside 6 '-N-Acetyltransferase from Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates
  Tomoe Kitao; Tohru Miyoshi-Akiyama; Teruo Kirikae
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 53, 6, 2327, 2334, Jun. 2009, [Peer-reviewed]
  English, Scientific journal
• KHM-1, a Novel Plasmid-Mediated Metallo-beta-Lactamase from a Citrobacter freundii Clinical Isolate
  Jun-ichiro Sekiguchi; Koji Morita; Tomoe Kitao; Noboru Watanabe; Mitsuhiro Okazaki; Tohru Miyoshi-Akiyama; Masato Kanamori; Teruo Kirikae
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 52, 11, 4194, 4197, Nov. 2008, [Peer-reviewed]
  English, Scientific journal
• The RGD motif in fibronectin is essential for development but dispensable for fibril assembly
  Seiichiro Takahashi; Michael Leiss; Markus Moser; Tomoo Ohashi; Tomoe Kitao; Dominik Heckmann; Alexander Pfeifer; Horst Kessler; Junichi Takagi; Harold P. Erickson; Reinhard Faessler
  JOURNAL OF CELL BIOLOGY, 178, 1, 167, 178, Jul. 2007, [Peer-reviewed]
  English, Scientific journal
• Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors
  Norihisa Yasui; Terukazu Nogi; Tomoe Kitao; Yoshimi Nakano; Mitsuharu Hattori; Junichi Takagi
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104, 24, 9988, 9993, Jun. 2007, [Peer-reviewed]
  English, Scientific journal
• Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha 1 beta 1 integrin
  Kazuhiro Suzuki; Tatsusada Okuno; Midori Yamamoto; R. Jeroen Pasterkamp; Noriko Takegahara; Hyota Takamatsu; Tomoe Kitao; Junichi Takagi; Paul D. Rennert; Alex L. Kolodkin; Atsushi Kumanogoh; Hitoshi Kikutani
  NATURE, 446, 7136, 680, 684, Apr. 2007, [Peer-reviewed]
  English, Scientific journal
• Display of alpha-amylase on the surface of Lactobacillus casei cells by use of the PgsA anchor protein, and production of lactic acid from starch
  J Narita; K Okano; T Kitao; S Ishida; T Sewaki; MH Sung; H Fukuda; A Kondo
  APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 72, 1, 269, 275, Jan. 2006, [Peer-reviewed]
  English, Scientific journal
• Structure of a closed-form uroporphyrinogen-III C-methyltransferase from Thermus thermophilus
  PH Rehse; T Kitao; TH Tahirov
  ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 61, Pt 7, 913, 919, Jul. 2005, [Peer-reviewed]
  English, Scientific journal
• Crystallization and preliminary crystallographic analysis of the nickel-responsive regulator NikR from Pyrococcus horikoshii
  T Kitao; C Kuroishi; TH Tahirov
  ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, 61, Pt 1, 43, 45, Jan. 2005, [Peer-reviewed]
  English, Scientific journal
• Crystal structure of purine nucleoside phosphorylase from Thermus thermophilus
  TH Tahirov; E Inagaki; N Ohshima; T Kitao; C Kuroishi; Y Ukita; K Takio; M Kobayashi; S Kuramitsu; S Yokoyama; M Miyano
  JOURNAL OF MOLECULAR BIOLOGY, 337, 5, 1149, 1160, Apr. 2004, [Peer-reviewed]
  English, Scientific journal

• 宿主ユビキチンリガーゼと相互作用するレジオネラエフェクターの機能解析
  科学研究費助成事業
  01 Apr. 2023 - 31 Mar. 2026
  北尾 公英
  重篤な肺炎を引き起こす病原細菌レジオネラは、IV型分泌装置を介して約300ものエフェクターと呼ばれる病原タンパク質群を宿主細胞に輸送することにより宿主システムを撹乱し感染を確立する。本研究では、これまでの研究から宿主ユビキチンリガーゼAと相互作用することが明らかとなった機能未知エフェクタータンパク質LpgXのレジオネラ感染における役割を明らかにすることを目的とし以下に示す2つの方向で研究を行なった。
  （1）宿主ユビキチンリガーゼAはマクロファージにおいてNLRP3をユビキチン化し、インフラマソーム活性のネガティブレギュレーターとして機能することが近年別の研究グループにより報告されている。そこで、まずレジオネラ感染がNLRP3のユビキチン化にどのような影響をあたえるのかをHEK293T細胞を用いて調べたところ、レジオネラ感染と非感染でNLRP3のユビキチン化レベルに若干の差異がみられたが、定量したところ、有意な差は認められなかった。
  （2）LpgXは予備実験から宿主ユビキチンリガーゼAと相互作用することが分かっているが、詳細なLC/MS-MS解析により別の宿主ユビキチンリガーゼCとも相互作用することが新たに判明した。宿主ユビキチンリガーゼAとCは宿主細胞内において複合体を形成することがしられ、この複合体形成はNEDD8を介した翻訳後修飾により制御されている。そこで、レジオネラ感染がこの複合体の形成にどのような影響を与えるのかを解析したところ、レジオネラ感染と非感染条件でこの複合体に差異は見られなかった。
  次年度は、THP-1由来のマクロファージを用いた実験系を構築し実験条件の検討を行い、引き続き研究を実施する予定である。
  日本学術振興会, 基盤研究(C), 岐阜大学, 23K06527
• 新しい細菌感染制御法開発に向けたIV型分泌装置の超分子構造解析
  Apr. 2020 - Mar. 2023
  北尾 公英
  立松財団, 基礎工学研究助成
• v-SNAREの翻訳後修飾を介した病原細菌の宿主細胞内生存戦略の解明
  科学研究費助成事業 基盤研究(C)
  Apr. 2020 - Mar. 2023
  北尾 公英
  レジオネラ感染初期に宿主小胞輸送における膜融合に関わるv-SNAREタンパク質がユビキチン化され、感染後期になるとそのユビキチン化がLotBによって解除（脱ユビキチン化）される。また、この感染後期における脱ユビキチン化プロセスは、LCV形成の際の膜融合を司るv-SNAREと細胞膜由来t-SNARE間の相互作用の解離を促進する。しかしながら、レジオネラ感染初期に何故v-SNAREがユビキチン化される必要があるのか、また、どの因子によってv-SNAREはユビキチン化されるのかについては明らかになっていない。
  本研究では、昨年度までにv-SNAREのユビキチン化を担うユビキチンリガーゼを同定した。同因子は真核細胞におけるATP依存的なユビキチン化反応とは全く異なるNAD依存的ユビキチンリガーゼ活性を有する。宿主v-SNAREはレジオネラ感染依存的に本来の仕事場である小胞体を離れて細胞膜由来t-SNAREと結合しLCV上に集積することが知られる。そこで本年度は、v-SNAREのユビキチン化の有無が、v-SNAREのLCV上への集積にどのような影響を与えるのかを調べた。その結果、ユビキチンリガーゼ存在下においてLCV上に集積するv-SNAREの割合は、ユビキチンリガーゼ非存在下におけるそれよりも有意に高いことが明らかとなった。本結果は、同定したユビキチンリガーゼによるv-SNAREのユビキチン化がv-SNAREのLCVへの集積を促進していることを強く示唆している。本実験以外には、同定したユビキチンリガーゼがin vitroにおいてv-SNAREをユビキチン化することを実証することができた。
  日本学術振興会, 基盤研究(C), 岐阜大学, 20K07477
• 病原因子を輸送中のIV型分泌装置を可視化する - レジオネラ感染機序の解明
  Jan. 2019 - Dec. 2020
  北尾 公英
  MSD財団女性研究者支援研究助成・感染症領域, Principal investigator, Competitive research funding
• COPI小胞を操作するレジオネラエフェクターの解析
  若手研究
  Apr. 2018 - Mar. 2020
  北尾 公英
  日本学術振興会 科学研究費助成事業, Principal investigator, Competitive research funding
• 細菌感染症制御に向けたIV型分泌装置の機能・構造解析
  特別研究員奨励費
  Apr. 2017 - Mar. 2020
  北尾 公英
  日本学術振興会 科学研究費助成事業, Principal investigator, Competitive research funding
• チオールプローブを用いたアミノグリコシド耐性菌迅速検出法の開発
  若手研究(B)
  Apr. 2012 - Mar. 2013
  北尾 公英
  日本学術振興会 科学研究費助成事業, Principal investigator, Competitive research funding
• 緑膿菌の細胞間シグナル伝達機構の解明
  海外留学助成金リサーチフェローシップ
  2013
  北尾 公英
  上原記念生命科学財団, Principal investigator, Competitive research funding
• 多剤耐性菌のアミノグリコシド耐性因子の解析
  疾病の治療方法、保健医療のEBMに資する研究2
  湯尾 明; 北尾 公英
  国際医療研究開発費, Principal investigator, Competitive research funding

• モノクローナル抗体、それを用いる検査装置
  Patent right, 秋山徹; 安藤公英; 斉藤 暢子; 切替 照雄; 田中 雅士; 楢原 謙次
  特願2011-109456, 16 May 2011
  特開2012-240923, 10 Dec. 2012
  特許5794450
  14 Oct. 2015