Application of autophagy-inducing factor Atg1 for candidiasis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagasaki University
• Principal Investigator: SHIMAMURA Shintaro 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (30547138)
• Co-Investigator(Kenkyū-buntansha): 宮崎 泰可 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60448496)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: カンジダ症 / オートファジー

Outline of Final Research Achievements

Autophagy was induced by nitrogen starvation and H2O2 in C. glabrata. A mutant strain lacking CgAtg1, an autophagy-inducing factor, was generated and confirmed to be deficient for autophagy. The Cgatg1 strain was sensitive to nitrogen starvation and H2O2, died rapidly in water without any nutrients, and showed high intracellular ROS levels compared with the wild-type strain and the CgATG1-reconstituted strain in vitro. Upon infecting mouse peritoneal macrophages, the Cgatg1 strain showed higher mortality from phagocytosis by macrophages. Finally, in vivo experiments were performed using two mouse models of disseminated candidiasis and intra-abdominal candidiasis. The Cgatg1 strain showed significantly decreased CFUs in the organs of the two mouse models. These results suggest that autophagy contributes to C. glabrata virulence by conferring resistance to unstable nutrient environments and immune defense of hosts, and that Atg1 is a novel fitness factor in Candida species.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

学術的意義としては、オートファジーはヒトや酵母でよく研究されているが、病原菌のオートファジーの研究は発展途上であり、Candida glabrataでAtg1の研究を行ったのは本研究が初であり、病原性とオートファジーの関係についての知見に貢献するものと考えられる。社会的意義については、オートファジーは患者の機能を高める観点でよく研究されているが、逆に、外敵側のオートファジー、特に常在菌を発症前に抑えることに本研究はつながり、臨床応用に役立つ成果と考えられる。