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Elucidation of lethal intravascular hemolysis mechanism in Clostridium perfringens sepsis

Research Project

Project/Area Number 17K10034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNihon University

Principal Investigator

SUZAKI Ai  日本大学, 医学部, 兼任講師 (90251454)

Co-Investigator(Kenkyū-buntansha) 早川 智  日本大学, 医学部, 教授 (30238084)
相澤 志保子  日本大学, 医学部, 准教授 (30513858)
TRINH DUYQUANG  日本大学, 医学部, 助教 (90647190)
神谷 茂  杏林大学, 医学部, 特任教授 (10177587)
大谷 郁  東海大学, 医学部, 准教授 (30377410)
Project Period (FY) 2017-04-01 – 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 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsウェルシュ菌 / 敗血症 / 血管内溶血 / 溶血毒 / θトキシン / サイトカイン / 急性呼吸窮迫症候群 / 感染症
Outline of Final Research Achievements

To elucidate the mechanism of massive intravascular hemolysis (MIH) in Clostridium perfringens sepsis, biological characteristics were compared in two groups: blood-derived strains from patients with MIH (group H) and those from patients without MIH.
The culture supernatant of group H have significantly higher hemolytic activity on human erythrocytes. Hemolytic effects were correlated withθ-toxin levels in culture supernatant of clinical isolates. θ-toxin also showed a significant correlation with cytotoxicity in human peripheral blood mononuclear cells (PBMCs) and IL-6 and IL-8 production from human PBMCs. Furthermore, θ-toxin induced production of TNF-α, IL-5, IL-6, and IL-8 more strongly than α-toxin. These results suggest that θ-toxin is one of the major virulence factors of lethal sepsis with MIH.

Academic Significance and Societal Importance of the Research Achievements

ウェルシュ菌による敗血症のうち広範な血管内溶血を伴う症例は、頻度は少ないものの予後が非常に悪く、現在でも致死的な疾患である。しかしその稀少性と極めて電撃的な経過をとるため生前診断が困難で、病原因子については長い間不明のままであった。また平均在院時間が8時間と極めて短時間であることから、現在の抗菌薬の治療では救命が極めて困難であることも知られている。
今回この病態の主要病原因子の一つとしてθ毒素の関与が明らかになった。今後他のClostridium属の治療と同様、抗菌薬以外にトキソイドを使用するなど、新たな治療法の開発に寄与できると考えられる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2021 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Pathogenic characterization of Clostridium perfringens strains isolated from patients with sepsis associated with massive intravascular hemolysis2021

    • Author(s)
      Ai Suzaki, Kaori Ohtani, Shihoko Komine-Aizawa, Asami Matsumoto, Shigeru Kamiya, Satoshi Hayakawa
    • Journal Title

      frontiers in Microbiology

      Volume: 12

    • DOI

      10.3389/fmicb.2021.713509

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ウェルシュ菌(Clostridium perfringens)菌血症20症例の臨床的検討2019

    • Author(s)
      須崎 愛, 赤羽目翔悟, 下口和雄, 西山宏幸
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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