Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex
Qinxin Zhang,
Wei Xian,
Zilin Li,
Qian Lu,
Xindi Chen,
Jinli Ge,
Zhiheng Tang,
Bohao Liu,
Zhe Chen,
Xiang Gao,
Michael O. Hottiger,
Peipei Zhang,
Jiazhang Qiu,
Feng Shao,
Xiaoyun Liu
Affiliations
Qinxin Zhang
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Wei Xian
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Zilin Li
National Institute of Biological Sciences, Beijing 102206, China
Qian Lu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Xindi Chen
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Jinli Ge
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Zhiheng Tang
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Bohao Liu
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Zhe Chen
State Key Laboratory of Microbial Technology, Microbial Technology Institute, School of Life Science, Shandong University, Qingdao 266000, China
Xiang Gao
State Key Laboratory of Microbial Technology, Microbial Technology Institute, School of Life Science, Shandong University, Qingdao 266000, China
Michael O. Hottiger
Department of Molecular Mechanisms of Disease, University of Zurich, 8057 Zurich, Switzerland
Peipei Zhang
Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Department of Biochemistry, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Corresponding author
Jiazhang Qiu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China; Corresponding author
Feng Shao
National Institute of Biological Sciences, Beijing 102206, China
Xiaoyun Liu
Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Corresponding author
Summary: 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.
