Latent infection of Helicobacter cinaedi in bone marrow sustained by reactive sulfur metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07554
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Tohoku University
• Principal Investigator: Matsunaga Tetsuro 東北大学, 医学系研究科, 助教 (00723206)
• Co-Investigator(Kenkyū-buntansha): 末田 大輔 熊本大学, 病院, 特任講師 (70750040)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Helicobacter cinaedi / 活性イオウ代謝 / 細胞内寄生 / 潜伏感染

Outline of Final Research Achievements

Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated to clarify the mechanism of pathogenesis in emerging infections by H. cineadi. We found that H. cinaedi persistently latent in the bone marrow in infected mice and enhance the pathogenesis of atherosclerosis. We also found that this bacterium parasitize intracellularly by avoiding from autophagic killing and hijacking of reactive persulfide-driven energy metabolism of mitochondria. These data provide the important findings for the elucidation of the theory of H. cinaedi infectious disease such as arteriosclerotic pathogenesis and the development of preventive / therapeutic methods.

Free Research Field

硫黄生物学

Academic Significance and Societal Importance of the Research Achievements

このような活性イオウによる親電子シグナルとオートファジーの制御およびイオウ呼吸によるミトコンドリア機能制御を基盤とした、H. cinaediの細胞内寄生性・骨髄内潜伏感染機構の解明は、全く独創的で革新的な研究アプローチである。以上より本研究の成果は、未解明な部分が多いH. cinaedi感染症における病原性発現機構の解明のみならず、動脈硬化症をはじめとする心血管疾患や生活習慣病・国民病の新たな予防・治療への応用に大きく貢献することが期待される。