Abstract：
Under stress conditions, translationally stalled mRNA and associated proteins undergo liquid-liquid phase separation and condense into cytoplasmic foci called stress granules (SGs). Many viruses hijack SGs for their pathogenesis; however, whether pathogenic bacteria also exploit this pathway remains unknown. Here, we report that members of the OspC family of Shigella flexneri induce SG formation in infected cells. Mechanistically, the OspC effectors target multiple subunits of the host translation initiation factor 3 complex by ADP-riboxanation. The modification of eIF3 leads to translational arrest and thus the formation of SGs. Furthermore, OspC-mediated SGs are beneficial for S. flexneri replication within infected host cells, and bacterial strains unable to induce SGs are attenuated for virulence in a murine model of infection. Our findings reveal a mechanism by which bacterial pathogens induce SG assembly by inactivating host translational machinery and promote bacterial proliferation in host cells.
摘要：
在应力条件下，翻译中停滞的mRNA和相关蛋白质经历液-液相分离并凝结成称为应激颗粒（SGs）的细胞质灶。许多病毒劫持SGs的发病机理；然而，致病菌是否也利用这一途径仍不得而知。这里,我们报道了福氏志贺氏菌OspC家族的成员在感染细胞中诱导SG的形成。机械上,OspC效应子通过ADP-羧化作用靶向宿主翻译起始因子3复合物的多个亚基。eIF3的修饰导致翻译停滞,从而形成SGs。此外，OspC介导的SGs有利于在受感染的宿主细胞内复制。和不能诱导SGs的细菌菌株在鼠感染模型中的毒力被减毒。我们的发现揭示了细菌病原体通过灭活宿主翻译机制诱导SG组装并促进宿主细胞中的细菌增殖的机制。
