The interference of host exosome releases by entropathogenic Escherichia coli

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19126
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Osaka University
• Principal Investigator: Yen Hilo 大阪大学, 医学系研究科, 助教 (50612066)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: EPEC / Effector / T3SS / Exosome / Immune response / infection / エクソソーム / EHEC

Outline of Final Research Achievements

Recently infected cells were found to releases nano-size membranous particles that deliver inflammatory molecules to neighboring cells. As EPEC and EHEC are known to actively interfere host immune responses, we set out to investigate whether EPEC/EHEC could regulate the biogenesis of exosomes. We found that upon challenges of non- or pathogenic Escherichia coli (E. coli), cells released increasing amount of exosomes compared to non-treated cells. Furthermore, pathogenic strains caused much larger releases than that of non-pathogenic strain. Such high releases of exosomes by pathogens-infected cells was attenuated when using a non-infectious mutant strain. To further elucidate potential bacterial molecules capable of regulating exosomes, we identified multiple EPEC virulent factors, including factor A with confirmed ability to influence the generation of exosomes in infected cells.

Free Research Field

微生物学

Academic Significance and Societal Importance of the Research Achievements

病原菌と宿主細胞の相互作用の強弱が感染症のアウトカムに繋がることが知られている。その中、エクソソームは細胞間の情報運び屋として働き、感染細胞の炎症情報を伝播する役割を果たしている。本研究を通して初めて腸管病原性大腸菌と腸管出血性大腸菌が積極的にエクソソームの産生を影響する現象を見出し、さらに干渉しうる病原菌タンパク質を複数同定できた。この事から、エクソソーム機構をうまくコントロールする事が病原菌にとって大切である事を意味する。よって、本研究より同定された病菌タンパク質の働きとその干渉メカニズムをさらに解析を進む事で、これらを標的とするより良い治療薬の開発に繋がる可能性がある。