Identification of EHEC virulent factors in exosome and its functional role during the infection

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07538
• 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: Osaka University
• Principal Investigator: Yen Hilo 大阪大学, 医学系研究科, 助教 (50612066)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: EPEC / inflammation / exosome / effector / T3SS

Outline of Final Research Achievements

Enteropathogenic Escherichia coli (EPEC) use its Type 3 secretion system (T3SS) to deliver virulent factors inside host cells. In a previous study, we have observed that EPEC infection induced a significant amount of exosome from the host cells. Recently, exosomes have been implicated in intracellular transmission of functionals molecules. However, how these exosomes contributed to the progression of EPEC infection is unknown. In current study, we found that the induction of exosome is dependent on the T3SS and that pharmacological inhibition of Caspase-4 could block T3SS-dependent induction of exosome. Lastly, we found a T3SS-associated virulent protein in exosomes. Functional studies showed that administration of these exosomes to non-infected cells allowed a higher attachment rate of EHEC compared to non-administrated cells. In all, current investigation showed the first time that EPEC induced exosome carrying a specific virulent factor to enhance secondary infection.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

EPEC はこれまでに直接感染した細胞に毒素を打ち込むことで、細胞の機能を制御することが知られている。本研究を介して、打ち込まれた毒素はエクソソームを介して他細胞に伝播し、その細胞に対する菌の接着率を高める効果がある事を初めて示した。EPEC感染を理解する上で、新しい見解を提供できるものである。さらに、感染細胞由来のエクソソームは感染の進行に正の働きをする事から、EPEC感染症の新規治療薬として、エクソソームは一つの標的になりうる可能性を示したことに意義が大きい。