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Host-pathogen interactions in antibiotic therapy for listeriosis

Research Project

Project/Area Number 18K07106
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionKanazawa University

Principal Investigator

Tsuchiya Kohsuke  金沢大学, がん進展制御研究所, 准教授 (50437216)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsパイロトーシス / インフラマソーム / ガスダーミンD / リステリア / inflammasome / pyroptosis / Listeria / AIM2 / 細菌感染治療 / 抗生物質 / GSDMD
Outline of Final Research Achievements

In macrophages infected, for example, by bacteria, the innate immune mechanism inflammasome is activated, which in turn induces the activation of the proteolytic enzyme caspase-1, leading to inflammatory programme cell death called pyrotosis. We found that the therapeutic effect of ampicillin administration during Listeria infection is promoted by an inflammasome and investigated the molecular mechanism of the improved therapeutic efficacy. We found that Listeria trapped within intracellular vacuoles become resistant to ampicillin treatment and prevent complete bacterial elimination, and that induction of pyrotosis is necessary to eliminate Listeria in the vacuoles. From this study, a co-ordinated action of antibiotic treatment and the immune system was revealed.

Academic Significance and Societal Importance of the Research Achievements

リステリアは汚染された食物を介して感染し、敗血症や髄膜炎といった重篤なリステリア症を引き起こす。リステリア症の治療には抗生物質が用いられるが依然として致死率が高い。リステリア症の第一選択薬はアンピシリンであるが、ゲンタマイシンなどとの併用が好ましいとされる。本研究は、インフラマソームを介したパイロトーシスの誘導がアンピシリンによる徹底した菌排除に必要であり、細胞内におけるアンピシリンとゲンタマイシンの併用効果の根底にあることを初めて明らかにした。さらに、小胞内に潜む細菌が抗生物質治療におけるリスク要因になり得ることを示した。これらの成果は適切な治療方針の決定に寄与するものである。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] 西南大学(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] 西南大学(中国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion2022

    • Author(s)
      Tanishita Yuko、Sekiya Hisateru、Inohara Naohiro、Tsuchiya Kohsuke、Mitsuyama Masao、Nunez Gabriel、Hara Hideki
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 8 Pages: 110414-110414

    • DOI

      10.1016/j.celrep.2022.110414

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gasdermin D mediates the maturation and release of IL-1α downstream of inflammasomes2021

    • Author(s)
      Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib M. R., Kinoshita T, Suda T
    • Journal Title

      Cell Rep.

      Volume: 34 Issue: 12 Pages: 108887-108887

    • DOI

      10.1016/j.celrep.2021.108887

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mint3 depletion-mediated glycolytic and oxidative alterations promote pyroptosis and prevent the spread of Listeria monocytogenes infection in macrophages2021

    • Author(s)
      Uematsu Takayuki、Tsuchiya Kohsuke、Kobayashi Noritada、Seiki Motoharu、Inoue Jun-ichiro、Kaneko Shuichi、Sakamoto Takeharu
    • Journal Title

      Cell Death and Disease

      Volume: 12 Issue: 4 Pages: 404-404

    • DOI

      10.1038/s41419-021-03691-y

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Switching from Apoptosis to Pyroptosis: Gasdermin-Elicited Inflammation and Antitumor Immunity2021

    • Author(s)
      Tsuchiya Kohsuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 1 Pages: 426-426

    • DOI

      10.3390/ijms22010426

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gasdermin D‐independent release of interleukin‐1 β by living macrophages in response to mycoplasmal lipoproteins and lipopeptides2020

    • Author(s)
      Saeki Ayumi、Tsuchiya Kohsuke、Suda Takashi、Into Takeshi、Hasebe Akira、Suzuki Toshihiko、Shibata Ken‐ichiro
    • Journal Title

      Immunology

      Volume: 161 Issue: 2 Pages: 114-122

    • DOI

      10.1111/imm.13230

    • NAID

      120007151366

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Caspase-7 mediates caspase-1-induced apoptosis independently of Bid.2020

    • Author(s)
      Mahib M.R., Hosojima S., Kushiyama H., Kinoshita T., Shiroishi T., Suda T.*, Tsuchiya K.
    • Journal Title

      Microbiology and Immunology

      Volume: 64 Issue: 2 Pages: 143-152

    • DOI

      10.1111/1348-0421.12756

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammasome-associated Cell Death: Pyroptosis, Apoptosis, and Physiological Implications.2020

    • Author(s)
      Tsuchiya K.
    • Journal Title

      Microbiology and Immunology

      Volume: In press Issue: 4 Pages: 252-269

    • DOI

      10.1111/1348-0421.12771

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Caspase-1 initiates apoptosis in the absence of gasdermin D2019

    • Author(s)
      Tsuchiya K, Nakajima S, SHosojima S, Nguyen DT, Hattori T, Le TM, Hori O, Mahib MR, Yamaguchi Y, Miura M, Kinoshita T, Kushiyama H, Sakurai M, Shiroishi T, Suda T
    • Journal Title

      Nature Communications

      Volume: In press Issue: 1 Pages: 2091-2091

    • DOI

      10.1038/s41467-019-09753-2

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism.2019

    • Author(s)
      Fang R., Uchiyama R., Sakai S., Hara H., Tsutsui H., Suda T., Mitsuyama M., Kawamura I., Tsuchiya K.
    • Journal Title

      Mucosal Immunology

      Volume: 12 Issue: 5 Pages: 1092-1103

    • DOI

      10.1038/s41385-019-0181-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Gasdermin D mediates the release and maturation of IL-1α during inflammasome formation.2021

    • Author(s)
      Kohsuke Tsuchiya, Takashi Suda.
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Pyroptosis enhances antibiotic therapy of listeriosis.2019

    • Author(s)
      Tsuchiya K, Suda T.
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Caspase-1 initiates apoptosis in the absence of gasdermin D.2019

    • Author(s)
      Tsuchiya K, Mahib MR, Suda T.
    • Organizer
      The 17th International Congress of Immunology (IUIS2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gasdermin D (GSDMD) mediates IL-1α maturation during inflammasome formation.2019

    • Author(s)
      Tsuchiya K, Suda T.
    • Organizer
      第 48 回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pyroptosis enhances killing of Listeria monocytogenes by ampicillin in vivo2018

    • Author(s)
      土屋晃介(筆頭演者)ほか
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Caspase-1 initiates apoptosis in the absence of gasdermin D2018

    • Author(s)
      土屋晃介(筆頭演者)ほか
    • Organizer
      第27回日本Cell Death学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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