The mechanism in transportation and inflammation of virulent factor which is carried by extracellular vesicles

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07481
• 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: Kyoto Prefectural University
• Principal Investigator: Oka Mayuko 京都府立大学, 生命環境科学研究科, 准教授 (40347498)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: extracellular vesicles / macrophage / Escherichia coli / inflammation / cytokine / collicin I receptor

Outline of Final Research Achievements

Extracellular vesicles (EVs) are considered to be an inflammatory factor in several acute and chronic inflammatory diseases. The present study shows that EVs (exosomes) from mouse macrophages (Mφ; RAW264.7) elicited by Escherichia coli K-12 strain-derived EVs increased in the expression of pro-inflammatory factors by uninfected Mφ. We identified E. coli protein, CirA (colicin Ia receptor) as such as an important factor in inflammatory responses from donor Mφ to recipient Mφ. The C-terminus of the CirA protein, which was relayed from E. coli-derived EVs to Mφ-derived exosomes, promoted exosome-mediated inflammatory responses by uninfected Mφ. Furthermore, CirA expression in E. coli increased under iron-limiting conditions (0.2 microM). Therefore, a low iron concentration would not only increase in the expression of CirA, but also enhance the inflammatory responses relayed by exosomes during E. coli infection of the host.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、大腸菌感染に伴う炎症が、大腸菌とマクロファージのそれぞれの細胞外小胞惹起され、新たな機構を明らかにした。これは、腸管上皮細胞が傷害を受けた時、腸内細菌叢の非病原性大腸菌が、細胞外小胞を介して炎症を惹起する可能性を示している。細菌の細胞外小胞が拡散する炎症は、既存の抗菌薬では治療できないため、これからの抗菌薬開発において、細菌の細胞外小胞は標的の1つになると考える。本研究成果で明らかにした宿主と細菌の新たな異種細胞間相互作用は、細菌感染症治療に新たな知見を与えると考える。