Shigella flexneri evades septin-mediated cell-autonomous immunity via protein ADP-riboxanation.

ABSTRACT: Cell-autonomous immunity represents evolutionarily conserved defense mechanisms present in both immune and non-immune cells. One of such mechanisms is mediated by cytoskeletal septins that entrap cytosolic bacterial pathogens within cage-like structures. To promote infection, Shigella flexneri delivers effector proteins directly into host cells via a type III secretion system. Here we demonstrate that OspC effectors enable Shigella flexneri to evade septin cage entrapment. Mechanistically, OspC catalyzes ADP-riboxanation of SEPT9 at Arg561, a site essential for stabilizing septin hetero-oligomers. Notably, Arg561 ADP-riboxanation impairs septin polymerization and hence assembly of higher-order structures, including filaments and cage-like structures. Furthermore, we provide evidence that O

SUBMITTER: Tang Z 

PROVIDER: S-EPMC12913881 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature