Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex

• Published in: Cell reports (Cambridge) Vol. 43; no. 2; p. 113789
• Main Authors: Zhang, Qinxin, Xian, Wei, Li, Zilin, Lu, Qian, Chen, Xindi, Ge, Jinli, Tang, Zhiheng, Liu, Bohao, Chen, Zhe, Gao, Xiang, Hottiger, Michael O., Zhang, Peipei, Qiu, Jiazhang, Shao, Feng, Liu, Xiaoyun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.02.2024; Elsevier
• Subjects: ADP-riboxanation; CP: Molecular biology; eIF3; OspC; Shigella flexneri; stress granules; stress granules; CP: Molecular biology; Shigella flexneri; OspC; ADP-riboxanation; eIF3
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113789

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. [Display omitted] •Shigella OspC family effectors ADP-riboxanate the eIF3 complex•Post-translational modifications of eIF3 inhibit host protein synthesis•OspCs induce stress granule formation different from classical eIF2α phosphorylation•Stress granules induced by OspCs promote bacterial replication during infection Zhang et al. found that Shigella OspC effectors target the eukaryotic translation initiation factor 3 (eIF3) complex by ADP-riboxanation. The modification of eIF3 leads to translational arrest and stress granule (SG) formation. Functionally, OspC-mediated SGs promote S. flexneri replication within infected host cells and contribute to bacterial virulence in vivo.