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Involvement in the pathogenic mechanism of Streptococcus pyogenes-derived extracellular vesicles

Research Project

Project/Area Number 20K07495
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Murase Kazunori  京都大学, 医学研究科, 助教 (40710869)

Co-Investigator(Kenkyū-buntansha) 菊地 泰生  宮崎大学, 医学部, 准教授 (20353659)
相川 知宏  京都大学, 医学研究科, 助教 (70725499)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords細胞外小胞 / A群レンサ球菌 / 細胞傷害性 / 免疫応答 / 病原機構 / 病原性メカニズム
Outline of Research at the Start

細胞外小胞(EVs)は、細菌が細胞外に放出する球状の構造体である。これらEVsの産生は細菌全体に備わっている生物学的プロセスであり、多様な病原因子のデリバリーシステムとして機能し、細菌の感染戦略や病原性発揮の観点から非常に重要な因子であると考えられている。本研究では、先行研究成果を基に、i)臨床分離株(劇症型・非劇症型)におけるEV産生量の把握、ii)EVに内包されるタンパクの網羅的な同定と、iii)In vitroにおけるEVの細胞傷害性と免疫応答の検討、iv)In vivoでのEV活性と宿主側との相互作用の解明を試みる。

Outline of Final Research Achievements

Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological functions including transport of virulence factors. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. Also, invasive GAS EVs showed slo-dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. Our findings indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.

Academic Significance and Societal Importance of the Research Achievements

EVsは多様な病原因子のデリバリーシステムとして機能し、細菌の感染戦略や病原性発揮の観点からも非常に重要な因子であると考えられているものの、その産生機構や宿主側との相互作用については、未だ不明な点が多い。そのため、EVsが直接的な病原性発揮機構の一つであることが明らかになれば、本研究の学術的意義は非常に大きい。さらに、EVsはワクチンとして利用することも可能である。近年、抗生物質耐性菌の増加など、細菌感染症に対する治療法の開発が急務であり、本研究による成果は、EVのワクチン応用のための効果的な利用法につながり、ワクチン開発における発展的な研究の一端になりうるため、社会的意義は高いと考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 Other

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

  • [Int'l Joint Research] INSERM/Toulouse University Hospital/INRA(フランス)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Wellcome Sanger Institute(英国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Clonal Expansion of Multidrug-Resistant <i>Streptococcus dysgalactiae</i> Subspecies <i>equisimilis</i> Causing Bacteremia, Japan, 2005?20212023

    • Author(s)
      Shinohara Koh、Murase Kazunori、Tsuchido Yasuhiro、Noguchi Taro、Yukawa Satomi、Yamamoto Masaki、Matsumura Yasufumi、Nakagawa Ichiro、Nagao Miki
    • Journal Title

      Emerging Infectious Diseases

      Volume: 29 Issue: 3 Pages: 528-539

    • DOI

      10.3201/eid2903.221060

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic dissection of the Vibrio cholerae O-serogroup global reference strains: reassessing our view of diversity and plasticity between two chromosomes2022

    • Author(s)
      Murase Kazunori、Arakawa Eiji、Izumiya Hidemasa、Iguchi Atsushi、Takemura Taichiro、Kikuchi Taisei、Nakagawa Ichiro、Thomson Nicholas R.、Ohnishi Makoto、Morita Masatomo
    • Journal Title

      Microbial Genomics

      Volume: 8 Issue: 8 Pages: 860-860

    • DOI

      10.1099/mgen.0.000860

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Global population structure of the Serratia marcescens complex and identification of hospital-adapted lineages in the complex2022

    • Author(s)
      Ono Tomoyuki、Taniguchi Itsuki、Nakamura Keiji、Nagano Debora Satie、Nishida Ruriko、Gotoh Yasuhiro、Ogura Yoshitoshi、Sato Mitsuhiko P.、Iguchi Atsushi、Murase Kazunori、Yoshimura Dai、Itoh Takehiko、Shima Ayaka、Dubois Damien、Oswald Eric、Shiose Akira、Gotoh Naomasa、Hayashi Tetsuya
    • Journal Title

      Microbial Genomics

      Volume: 8 Issue: 3

    • DOI

      10.1099/mgen.0.000793

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytolysin A (ClyA): A Bacterial Virulence Factor with Potential Applications in Nanopore Technology, Vaccine Development, and Tumor Therapy2022

    • Author(s)
      Murase Kazunori
    • Journal Title

      Toxins

      Volume: 14 Issue: 2 Pages: 78-78

    • DOI

      10.3390/toxins14020078

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological Effect of Streptococcus pyogenes-Released Extracellular Vesicles on Human Monocytic Cells, Induction of Cytotoxicity, and Inflammatory Response2021

    • Author(s)
      Murase Kazunori、Aikawa Chihiro、Nozawa Takashi、Nakatake Ayako、Sakamoto Kuniyo、Kikuchi Taisei、Nakagawa Ichiro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 711144-711144

    • DOI

      10.3389/fcimb.2021.711144

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Intraspecific genome diversity of Streptococcus dysgalactiae and the evolutional process with host switching2022

    • Author(s)
      村瀬一典
    • Organizer
      第95回細菌学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] A群レンサ球菌が産生する細胞外小胞の病原性への関与2021

    • Author(s)
      村瀬一典
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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