Xu Y Zhou P Cheng S Lu Q Nowak K Hopp AK Li L Shi X Zhou Z Gao W Li D He H Liu X Ding J Hottiger MO Shao F 2019 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 ΔsopF resembled S. flexneri ΔvirAΔicsB 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. application/pdf https://sonar.ch/global/documents/271330 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2019.06.007 info:eu-repo/semantics/altIdentifier/pmid/31327526 info:eu-repo/semantics/openAccess Cell. - 2019 ADP-ribosylation V-ATPase autophagy bacteria-host interaction innate immunity type III secretion system xenophagy ADP-Ribosylation Autophagy-Related Proteins Bacterial Proteins CRISPR-Cas Systems Gene Editing HeLa Cells Humans Macroautophagy Microtubule-Associated Proteins Protein Binding Salmonella Type III Secretion Systems Vacuolar Proton-Translocating ATPases Virulence Factors A Bacterial Effector Reveals the V-ATPase-ATG16L1 Axis that Initiates Xenophagy. http://purl.org/coar/resource_type/c_6501