A Salmonella Effector Reveals the V-ATPase-ATG16L1 Axis that Initiates Bacterial Autophagy

论文摘要

Antibacterial autophagy（xenophagy） is an important host defense, but how it is initiated is unclear. Here we performed a bacterial transposon screen and identified a T3SS effector SopF that potently blocked Salmonella autophagy. SopF was a general xenophagy inhibitor without affecting canonical autophagy. S. Typhimurium ?sopF resembled S. flexneri ?virA?icsB with the majority of intracellular bacteria targeted by autophagy, which permitted a CRISPR screen to identify host V-ATPase as an essential factor. Upon bacteria-triggered vacuolar damage, the V-ATPase recruited ATG16L1 onto bacteria-containing vacuole, which was blocked by SopF. Mammalian ATG16L1 bears a WD40 domain that was required for interacting with the V-ATPase. Inhibiting autophagy by SopF promoted S. Typhimurium proliferation in vivo. SopF targeted Gln124 of ATP6V0 C in the V-ATPase for ADP-ribosylation. Mutation of Gln124 also blocked xenophagy but not canonical autophagy. Thus, the discovery of SopF reveals the V-ATPase-ATG16L1 axis that critically mediates autophagic recognition of intracellular pathogen.

论文目录

文章来源

类型: 国内会议

作者: Yue Xu,Ping Zhou,Jingjin Ding,Sen Cheng,Michael Hottiger,Feng Shao

来源: 中国生物化学与分子生物学会2019年全国学术会议暨学会成立四十周年 2019-10-24

年度: 2019

分类: 基础科学

专业: 生物学

单位: National Institute of Biological SciencesCollege of Biological Sciences, China Agricultural UniversityInstitute of Biophysics, Chinese Academy of SciencesCollege of Chemistry and Molecular Engineering,Peking UniversityDepartment of Molecular Mechanisms of Disease, University of Zurich

分类号: Q935

页码: 130

总页数: 1

文件大小: 772k

下载量: 18

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