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Functional elucidation of novel effectors of Legionella pneumophila approached through interactions with unique ciliate

Research Project

Project/Area Number 22K07051
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Okubo Torahiko  北海道大学, 保健科学研究院, 講師 (90762196)

Co-Investigator(Kenkyū-buntansha) 中村 眞二  順天堂大学, 大学院医学研究科, 助教 (40207882)
山口 博之  北海道大学, 保健科学研究院, 教授 (40221650)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsレジオネラ / 繊毛虫 / 微生物間相互作用
Outline of Research at the Start

レジオネラは浴室の空気を介して肺炎を起こす病原菌である。これまではレジオネラとアメーバの共培養から病原性の検証が行なわれてきたが、その全容はまだ明らかではない。本研究では、レジオネラによって殺滅されてしまうユニークな繊毛虫Anteglaucomaと遺伝子組換えレジオネラの共培養実験を行ない、レジオネラがもつ未知の病原性因子の検出を行なう。得られた成果は将来的にレジオネラ感染症の制御につながると期待される。

Outline of Final Research Achievements

To search for novel virulence factors of Legionella pneumophila (Lp), we performed co-culture experiments of Lp with Anteglaucoma, a ciliate that dies rapidly upon Lp infection. Co-culturing of ciliates with transposon insertion mutants of Lp (n=782) resulted in the selection of mutants that do not kill ciliates and the identification of novel candidate virulence factors (n=7), excluding known virulence factors. Co-cultures with human cells (HeLa, THP-1) showed that all candidate factors were virulence factors acting only on ciliates. The unique ciliate-Lp co-culture allowed us to identify novel functions of several effector molecules of Lp and to elucidate some of the survival strategies of Lp in the natural environment.

Academic Significance and Societal Importance of the Research Achievements

本研究ではヒト病原細菌のLegionella pneumophila(レジオネラ)と、レジオネラに殺滅されるユニークな繊毛虫Anteglaucomaとの共培養系を確立し、ヒト上皮細胞や繊毛虫に作用する病原因子(n=7)を特定した。これらの存在自体は既知であるが、上皮細胞や繊毛虫への病原性は未報告であることから、レジオネラがもつ病原因子の新たな機能を見出すことができた。この成果は、レジオネラの病態形成や自然環境中での生存性向上に寄与する因子に関する知見を提供するものであり、レジオネラの病態増悪メカニズムや感染源の特定または予防策の基礎につながるものと考えられる。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (4 results)

All 2024 2023 2022

All Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] 野外繊毛虫を用いたレジオネラの新規病原因子の探索とその解析2024

    • Author(s)
      大久保寅彦, 山口博之
    • Organizer
      第97回日本細菌学会総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 繊毛虫の殺滅現象を利用したLegionella pneumophila の 新規病原因子の探索2023

    • Author(s)
      大久保寅彦、山口博之
    • Organizer
      第96回日本細菌学会総会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Interaction between Legionella pneumophila and ciliate Anteglaucoma , which is killed by co-culturing2022

    • Author(s)
      Okubo T, Kawashiro A, Gengyo R, Tanishi R, Yamaguchi H.
    • Organizer
      The 10th International Conference on Legionella
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Molecular Mechanism by Which Legionella Pneumophila JR32 Instantly Kills Anteglaucoma Harbinensis CS11A, a Ciliate Isolated from Sewage2022

    • Author(s)
      Okubo T.
    • Organizer
      ASM Microbe 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2026-01-16  

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