细菌效应体揭示了V-ATPase-ATG16L1系统，该系统启动了异源吞噬，这一成果由清华大学邵峰研究组取得。这一研究成果于2019年7月25日发表在国际学术期刊《细胞》上。

该团队进行了细菌转座子筛选，并确定了一个沙门氏菌III型分泌系统（T3SS）效应蛋白SopF，能够有效阻止沙门氏菌的自噬。SopF是一种不影响经典自噬途径的常用异源自噬抑制剂。鼠伤寒沙门氏菌ΔSopF与挠曲沙门氏菌ΔvirAΔicsB相似，是大多数细胞内细菌自噬目标，研究者通过CRISPR筛选，发现宿主V-ATPase是自噬的必要因素。当细菌引起液泡损伤时，V-ATPase将ATG16L1引入含有细菌的液泡中，该过程能够被SopF阻断。哺乳动物ATG16L1具有与V-ATPase相互作用所需的WD40结构域。通过SopF抑制自噬，可促进鼠伤寒杆菌的体内增殖。SopF以V-ATPase中的ATP6V0C的124位谷氨酰胺为靶点，促使其进行ADP核糖基化。124位谷氨酰胺的突变也能够阻止异源自噬，但不能阻止经典自噬。因此，SopF的发现揭示了ATPase-ATG16L1这一对细胞内病原体的自噬识别起关键性作用的系统。

据悉，异源自噬(xenophagy)是一种重要的宿主防御手段，但是尚不清楚该过程是如何开始的。

附：英文原文

Title: A Bacterial Effector Reveals the V-ATPase-ATG16L1 Axis that Initiates Xenophagy

Author: Yue Xu, Ping Zhou, Sen Cheng, Jingjin Ding, Michael O.Hottiger, Feng Shao

Issue&Volume: 25 JULY 2019

Abstract: 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 Δ sopF resembled S. flexneri Δ virAΔ icsB with the majority of intracellular bacteria targeted by autophagy, permitting a CRISPR screen that identified host V-ATPase as an essential factor. Upon bacteria-caused vacuolar damage, the V-ATPase recruited ATG16L1 onto bacteria-containing vacuole, which was blocked by SopF. Mammalian ATG16L1 bears a WD40 domain required for interacting with the V-ATPase. Inhibiting autophagy by SopF promoted S. Typhimurium proliferation in vivo. SopF targeted Gln124 of ATP6V0C 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.

DOI: https://doi.org/10.1016/j.cell.2019.06.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30635-X