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Molecular epidemiology and mechanism of quorum sensing system in C. difficile

Research Project

Project/Area Number 19K08949
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionThe University of Tokyo

Principal Investigator

OKUGAW SHU  東京大学, 医学部附属病院, 准教授 (20376461)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsC. difficile / クオラムセンシング / agr / accessory gene regulator / agr遺伝子 / CRISPR-Cas9 / Clostridioides difficile / quorum sensing / 分子疫学 / 機能 / クロストリジウム
Outline of Research at the Start

C. difficile感染症は近年強毒株による重篤化や治療後の再発など新たな問題が出現し、さらなる治療法の研究、開発が望まれる。
申請者らはC. difficileのクオラムセンシング機構に着目し、その機構を介した病原因子制御を解明することにより、新たな治療戦略を見出すことを本研究の目的とする。これまで詳細に検討されていない臨床分離株を用いたC. difficileのクオラムセンシング機構関連遺伝子の分子疫学的解析を行い、病態との関連を検証する。さらに、クオラムセンシング機構の微生物学的な病原性への影響とその機序解明、新たな治療戦略を検証する。

Outline of Final Research Achievements

C. difficile is the causative agent of antibiotic-associated diarrhea. Toxins produced by C. difficile are essential virulence to cause enteritis. In recent years, the emergence of hypervirulent strains has become a global problem. In this study, we found that the agr quorum-sensing mechanism that regulates toxin production has genetic diversity.

Academic Significance and Societal Importance of the Research Achievements

高齢化や医療の高度化でC.difficile感染症の再発や重症化は今後も世界的問題になると考えられる。本研究で示されたC. difficileの主たる病原因子である毒素の産生制御機構が遺伝的多様性を有していることは、菌株によって発症要因が異なる可能性を示した点で学術的意義がある。本知見は毒素産生をターゲットとした治療薬開発に貢献する可能性を秘めている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019

All Journal Article (26 results) (of which Peer Reviewed: 21 results,  Open Access: 18 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] A Cold-Blooded Tiptoer: class FormattedString { value: Nonresolving Cellulitis in an Immunocompromised Patient }2022

    • Author(s)
      Kitaura Satoshi、Okamoto Koh、Wakabayashi Yoshitaka、Okada Yuta、Okazaki Aiko、Ikeda Mahoko、Okugawa Shu、Fujimoto Fumie、Bujo Chie、Minatsuki Shun、Tsushima Kensuke、Chikamatsu Kinuyo、Mitarai Satoshi、Moriya Kyoji
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 9 Issue: 4

    • DOI

      10.1093/ofid/ofac074

    • URL

      https://localhost/en/publications/b364c725-0e39-4f77-8d0a-d8e1dc44710c

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urine sediment findings were milder in patients with COVID-19-associated renal injuries than in those with non-COVID-19-associated renal injuries2022

    • Author(s)
      Morita Yoshifumi、Kurano Makoto、Jubishi Daisuke、Ikeda Mahoko、Okamoto Koh、Tanaka Masami、Harada Sohei、Okugawa Shu、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      International Journal of Infectious Diseases

      Volume: 117 Pages: 302-311

    • DOI

      10.1016/j.ijid.2022.02.024

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report2022

    • Author(s)
      Yamashita Marie、Ikeda Mahoko、Kato Ito、Ohama Yuki、Ando Mizuo、Ikemura Masako、Jubishi Daisuke、Kanno Yoshiaki、Okamoto Koh、Umeyama Takashi、Nakamura Shigeki、Miyazaki Yoshitsugu、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Annals of Clinical Microbiology and Antimicrobials

      Volume: 21 Issue: 1 Pages: 5-5

    • DOI

      10.1186/s12941-022-00495-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] First Reported Human Case of Spondylodiscitis by <i>Staphylococcus condimenti</i>: A Case Report and Literature Review2021

    • Author(s)
      Kobayashi T, Nakajima K, Oshima Y, Ikeda M, Kitaura S, Ikeuchi K, Okamoto K, Okada Y, Ohama Y, Higurashi Y, Okugawa S, Moriya K.
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 4 Pages: 635-637

    • DOI

      10.2169/internalmedicine.5180-20

    • NAID

      130007986378

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-02-15
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical and Microbiological Characteristics of Recurrent Escherichia coli Bacteremia2021

    • Author(s)
      Kobayashi Tatsuya、Ikeda Mahoko、Okada Yuta、Higurashi Yoshimi、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Microbiology Spectrum

      Volume: 9 Issue: 3

    • DOI

      10.1128/spectrum.01399-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The prevalence of the iutA and ibeA genes in Escherichia coli isolates from severe and non-severe patients with bacteremic acute biliary tract infection is significantly different2021

    • Author(s)
      Ikeda Mahoko、Kobayashi Tatsuya、Fujimoto Fumie、Okada Yuta、Higurashi Yoshimi、Tatsuno Keita、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Gut Pathogens

      Volume: 13 Issue: 1 Pages: 32-32

    • DOI

      10.1186/s13099-021-00429-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Disseminated Gonococcal Infection in a Japanese Man with Novel C5 Gene Mutation.2021

    • Author(s)
      Ikeuchi, K., Okamoto, K., Inoue, N., Okugawa, S., Moriya, K.
    • Journal Title

      J Clin Immunol

      Volume: 41 Issue: 3 Pages: 691-693

    • DOI

      10.1007/s10875-020-00959-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changing trends in lipid profile and biomarkers of renal function and bone metabolism before and after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: a prospective observational study2021

    • Author(s)
      Ikeda Mahoko、Wakabayashi Yoshitaka、Okamoto Koh、Yanagimoto Shintaro、Okugawa Shu、Moriya Kyoji
    • Journal Title

      AIDS Research and Therapy

      Volume: 18 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s12981-021-00354-y

    • URL

      https://pure.teikyo.jp/en/publications/8a3f510b-b430-4f77-a1f4-01c405c1eeaf

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incidence and Risk Factors for Inappropriate Use of Non-Culture-Based Fungal Assays: Implication for Diagnostic Stewardship2021

    • Author(s)
      Ito Hiroshi、Okamoto Koh、Yamamoto Shinya、Yamashita Marie、Kanno Yoshiaki、Jubishi Daisuke、Ikeda Mahoko、Harada Sohei、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 9 Issue: 1

    • DOI

      10.1093/ofid/ofab601

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] First human case of catheter-related blood stream infection caused by Staphylococcus schleiferi subspecies coagulans: a case report and literature review2021

    • Author(s)
      Kobayashi Tatsuya、Ikeda Mahoko、Ohama Yuki、Murono Koji、Ikeuchi Kazuhiko、Kitaura Satoshi、Okamoto Koh、Okugawa Shu、Ishihara Soichiro、Moriya Kyoji
    • Journal Title

      Annals of Clinical Microbiology and Antimicrobials

      Volume: 20 Issue: 1 Pages: 68-68

    • DOI

      10.1186/s12941-021-00474-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plesiomonas shigelloides Septic Shock Following Ingestion of Dojo Nabe (Loach Hotpot)2021

    • Author(s)
      Shinohara Takayuki、Okamoto Koh、Koyano Saho、Otani Amato、Yamashita Marie、Wakimoto Yuji、Jubishi Daisuke、Hashimoto Hideki、Ikeda Mahoko、Harada Sohei、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 8 Issue: 8

    • DOI

      10.1093/ofid/ofab401

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clot waveform of APTT has abnormal patterns in subjects with COVID-192021

    • Author(s)
      Shimura Takuya、Kurano Makoto、Kanno Yoshiaki、Ikeda Mahoko、Okamoto Koh、Jubishi Daisuke、Harada Sohei、Okugawa Shu、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 5190-5190

    • DOI

      10.1038/s41598-021-84776-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe cellulitis caused by Achromobacter xylosoxidans after allogeneic hematopoietic stem cell transplantation2021

    • Author(s)
      Oyama Yu、Yasunaga Megumi、Honda Akira、Maki Hiroaki、Masamoto Yosuke、Kobayashi Tatsuya、Wakabayashi Yoshitaka、Okugawa Shu、Moriya Kyoji、Kurokawa Mineo
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 27 Issue: 5 Pages: 770

    • DOI

      10.1016/j.jiac.2020.12.025

    • URL

      https://localhost/en/publications/d4184b2d-a7e9-489b-8e85-f101ce937ecc

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic diversity and epidemiology of accessory gene regulator loci in Clostridioides difficile2020

    • Author(s)
      Yuta Okada, Shu Okugawa, Mahoko Ikeda, Tatsuya Kobayashi, Ryoichi Saito, Yoshimi Higurashi, Kyoji Moriya
    • Journal Title

      Access Microbiology

      Volume: (2)7 Issue: 7

    • DOI

      10.1099/acmi.0.000134

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of deoxycholate on Clostridioides difficile growth, toxin production, and sporulation2020

    • Author(s)
      Usui Y, Ayibieke A, Kamiichi Y, Okugawa S, Moriya K, Tohda S, Saito R.
    • Journal Title

      Heliyon

      Volume: 6(4) Issue: 4 Pages: e03717-e03717

    • DOI

      10.1016/j.heliyon.2020.e03717

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microbiological analysis of infectious lymphocele: Case series and literature review.2020

    • Author(s)
      Yamamoto S, Ikeda M, Kanno Y, Okamoto K, Okugawa S, Moriya K.
    • Journal Title

      J Infect Chemother.

      Volume: 27(2) Issue: 2 Pages: 172-178

    • DOI

      10.1016/j.jiac.2020.08.021

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute Pancreatitis During COVID-19 Pneumonia.2020

    • Author(s)
      Shinohara T, Otani A, Yamashita M, Wakimoto Y, Jubishi D, Okamoto K, Kanno Y, Ikeda M, Ishigaki K, Nakai Y, Harada S, Okugawa S, Koike K, Moriya K.
    • Journal Title

      Pancreas

      Volume: 49(10) Issue: 10 Pages: e106-e108

    • DOI

      10.1097/mpa.0000000000001695

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vibrio fluvialis liver abscess and bacteremia in a sashimi lover: A case report and review of the literature2020

    • Author(s)
      Kitaura S, Okamoto K, Wakabayashi Y, Okada Y, Okazaki A, Ikeda M, Hakuta R, Nakai Y, Okugawa S, Koike K, Moriya K.
    • Journal Title

      Open Forum Infect Dis.

      Volume: 7 Issue: 6

    • DOI

      10.1093/ofid/ofaa212

    • URL

      https://pure.teikyo.jp/en/publications/77a973fd-a830-4d95-b0ab-2f0b458ae109

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiology and virulence-associated genes of Clostridioides difficile isolates and factors associated with toxin EIA results at a university hospital in Japan2020

    • Author(s)
      Okada Yuta、Yagihara Yuka、Wakabayashi Yoshitaka、Igawa Gene、Saito Ryoichi、Higurashi Yoshimi、Ikeda Mahoko、Tatsuno Keita、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Access Microbiology

      Volume: 2 Issue: 2 Pages: 1-9

    • DOI

      10.1099/acmi.0.000086

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Poor penetration of cefcapene into aqueous humor after oral administration of cefcapene pivoxil to patients undergoing cataract surgery2020

    • Author(s)
      Okamoto Koh、Asano Shotaro、Yamamoto Takehito、Toyono Tetsuya、Yamaguchi Ryo、Okada Yuta、Okugawa Shu、Suzuki Hiroshi、Moriya Kyoji、Aihara Makoto
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 2 Pages: 312-315

    • DOI

      10.1016/j.jiac.2019.08.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【ウイルス肝炎アップデート】ウイルス性肝炎のトピックス しばしば見かける肝炎ウイルス以外のウイルス感染症による肝機能障害2020

    • Author(s)
      岡田 雄大, 奥川 周
    • Journal Title

      診断と治療

      Volume: 108 Pages: 253-256

    • Related Report
      2019 Research-status Report
  • [Journal Article] Clinical Features of Bloodstream Infections Associated With Peripheral Versus Central Venous Catheters2019

    • Author(s)
      Keita Tatsuno, Mahoko Ikeda, Yoshitaka Wakabayashi, Shintaro Yanagimoto, Shu Okugawa, Kyoji Moriya
    • Journal Title

      Infectious Diseases and Therapy

      Volume: 8 Issue: 3 Pages: 343-352

    • DOI

      10.1007/s40121-019-00257-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: class FormattedString { value: Case report and review of literature }2019

    • Author(s)
      Miyashita Hirotaka、Okamoto Koh、Kobayashi Tatsuya、Wakabayashi Yoshitaka、Kitaura Satoshi、Ikeuchi Kazuhiko、Ishigaki Kazunaga、Nakai Yosuke、Okugawa Shu、Koike Kazuhiko、Moriya Kyoji
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 6 Pages: 473

    • DOI

      10.1016/j.jiac.2019.01.007

    • URL

      https://localhost/en/publications/57b1b5e1-b078-4bc0-b33f-b3b5e0b5f9ed

    • Related Report
      2019 Research-status Report
  • [Journal Article] Fusobacterium necrophorum septic pelvic thrombophlebitis after intrauterine device insertion2019

    • Author(s)
      Yamamoto Shinya、Okamoto Koh、Okugawa Shu、Moriya Kyoji
    • Journal Title

      International Journal of Gynecology & Obstetrics

      Volume: 145 Issue: 1 Pages: 122-123

    • DOI

      10.1002/ijgo.12760

    • Related Report
      2019 Research-status Report
  • [Journal Article] A rare case of a prostatic abscess, bacteremia and chronic granulomatous disease associated with Klebsiella pneumoniae2019

    • Author(s)
      Wakabayashi Yoshitaka、Jubishi Daisuke、Okamoto Koh、Ikeda Mahoko、Tatsuno Keita、Mizoguchi Miyuki、Sato Tomoaki、Okugawa Shu、Moriya Kyoji
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 5 Pages: 365

    • DOI

      10.1016/j.jiac.2018.11.015

    • URL

      https://pure.teikyo.jp/en/publications/987b4d5e-cc35-47cb-9fc0-5033ef3db447

    • Related Report
      2019 Research-status Report
  • [Journal Article] 感染症の病原体核酸検査の現状と将来展望 細菌感染症診療における遺伝子検査 感染症専門医の立場から2019

    • Author(s)
      池田 麻穂子, 奥川 周, 森屋 恭爾
    • Journal Title

      臨床病理

      Volume: 67 Pages: 1179-1185

    • Related Report
      2019 Research-status Report
  • [Presentation] Clinical and Microbiological Differences in Recurrent Escherichia coli Bacteremia Is Dependent on the Bacteria Genetic Identity2021

    • Author(s)
      T. Kobayashi, M. Ikeda, Y. Okada, Y. Higurashi, S. Okugawa, K. Moriya
    • Organizer
      WORLD MICROBE FORUM 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 繰り返す大腸菌菌血症における遺伝的相同性の有無による臨床的・微生物学的特徴の検討2021

    • Author(s)
      小林 竜也、池田 麻穂子、岡田 雄大、日暮 芳己、奥川 周、森屋 恭爾
    • Organizer
      第70回日本感染症学会東日本地方会学術集会・第68回日本化学療法学会東日本支部総会合同学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Genetic Diversity and Epidemiology of Accessory Gene Regulator Loci in the Clinical Isolates of Clostridioides Difficile2020

    • Author(s)
      Yuta Okada, Shu Okugawa, Mahoko Ikeda, Tatsuya Kobayashi, Ryoichi Saito, Yoshimi Higurashi, Kyoji Moriya
    • Organizer
      ASM microbe 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] リンパ嚢胞感染の微生物学的検討:当院での8年 間における症例検討とliterature review2019

    • Author(s)
      山本 真也、池田麻穂子、菅野 芳明、岡本 耕、奥川 周、森屋 恭爾
    • Organizer
      第68回日本感染症学会東日本地方会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] .生焼けのサバ摂取後に発症した Raoultella ornithi nolytica 菌血症2019

    • Author(s)
      伊東 完,岡本 耕,山本 真也 山下麻梨絵,菅野 芳明,池田麻穂子 奥川 周,森屋 恭爾
    • Organizer
      第68回日本感染症学会東日本地方会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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