Analysis of pneumococci-induced autophagy aiming at the development of drug discoivery for IPD-treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07568
• 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: National Institute of Infectious Diseases
• Principal Investigator: Ogawa Michinaga 国立感染症研究所, 細菌第一部, 室長 (80361624)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肺炎球菌 / 病原性 / オートファジー

Outline of Final Research Achievements

We have previously reported that intracellular pneumococci are detected by hierarchical autophagic processes that ultimately lead to bacterial elimination. However, it remains unclear whether intracellular pneumococci can evade autophagy by deploying their own virulence factors. In this study, we investigated the biological functions of Cbps and found that CbpC-activated autophagy occurs via its interactions with autophagy-related (ATG)14 and sequestosome (SQSTM)1/p62. In pneumococcal-infected cells, ATG14 levels were dramatically reduced in a CbpC-dependent manner, resulting in suppression of autophagy-mediated degradation and enhanced bacterial survival. These results reveal a novel mechanism by which pneumococci can manipulate host autophagy responses, in this case by using CbpC as a decoy to promote ATG14 degradation.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究により、細胞内に侵入した肺炎球菌は宿主の殺菌機構から逃れるために病原因子CbpCをおとりにしてAtg14を分解することによりゼノファジーを抑制していることが明らかになった。肺炎球菌感染細胞において、菌体から放出された病原因子が宿主因子との相互作用を介して病原性を発揮することを解明したのは本研究が世界で初めてである。本研究の成果は次世代肺炎球菌ワクチン開発および新規予防法・治療法開発に必要な肺炎球菌が保有する病原因子に関する分子基盤構築に寄与するものとである。