Environmental adaptation mechanisms of Clostridium difficile (CD)

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SAITO Ryoichi 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00581969)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: クロストリジウム・ディフィシル / デオキシコール酸 / 芽胞 / 毒素 / ラクトバシラス属 / 環境適応

Outline of Final Research Achievements

Clostridium difficile causes a spectrum of symptoms, ranging from mild diarrhea to severe pseudomembranous colitis and even death. C. difficile infection (CDI) is a well-known cause of health-care-associated infectious diarrhea related to the disruption of the indigenous intestinal microbiota due to prolonged drug treatment. We found that: DCA inhibited efficient C. difficile vegetative growth in a dose-dependent manner; DCA regulated toxin production under vegetative growth conditions by repressing tcdB expression; DCA reduced C. difficile sporulation efficiency via spo0A downregulation; and DCA downregulated spore coat-related genes. Furthermore, we also demonstrated that Lactobacillus leichmunnii strain ATCC 7830 impacted the C. difficile gene expressions such as toxin production, amino acid metabolism, and membrane transport.

Free Research Field

細菌学、感染症

Academic Significance and Societal Importance of the Research Achievements

CD感染症は先進国に加え、近年は途上国でも増加が認められるため、世界的に注視すべき重要な感染症である。本研究により、CDの環境適応機構で最も重要な発芽・芽胞形成に関わる生理学的機構や臨床にも有益な毒素産生機構の基盤情報を提供できた。これらの成果は、上記の機構に関わる主要タンパク質の機能解析等を通して、CD感染症の新たな治療戦略や感染対策についても貢献できる可能性を示す。