Mechanism of inhibition of host autolysosome formation by stimulation of T. cruzi infection.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16626
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Gunma University
• Principal Investigator: Onizuka Yoko 群馬大学, 大学院保健学研究科, 助教 (30710058)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: Trypanosoma cruzi / SNARE 複合体 / オートファジー

Outline of Final Research Achievements

In Trypanosoma cruzi-infected cells, the initial process of autophagy is activated but not completed and the protozoa survive without being eliminated. In this study, the SNARE complexes (stx17, VAMP8 and SNAP29) involved in autolysosome formation were analyzed. The results suggest that stx17, which is on autophagosomes, was degraded and reduced in T. cruzi-infected cells and that its function could be suppressed. Next, to search for protozoan factors that interact with the stx17 protein, a proteomic analysis by mass spectrometry was performed, and several candidate factors were identified. Knockout T. cruzi of the identified candidate factors were generated and the derived protozoa are currently being analyzed.

Free Research Field

分子寄生虫学

Academic Significance and Societal Importance of the Research Achievements

シャーガス病は、感染から数十年経後に慢性期の症状を呈するが、なぜ長期に渡り、患者体内での感染を維持できるか明らかにされておらず、宿主オートファジー抑制機構の解明は、原虫の長期持続感染機構解明の一助になると考えている。また、心疾患や消化管疾患などの慢性期の病態形成の詳しい機構も未だ明らかにされていない。本研究では、宿主オートファジー抑制の可能性を持つ、原虫側因子を同定することができた。今後詳細な研究を進めることにより、病態形成メカニズムの新たな知見が得られ、新しい治療薬候補の開発への応用も期待できる。