title: The Salmonella effector SopB prevents ROS-induced apoptosis of epithelial cells by retarding TRAF6 recruitment to mitochondria.
abstract: Microbial pathogens enter host cells by injecting effector proteins of the Type III secretion system (T3SS), which facilitate pathogen translocation across the host cell membrane. These effector proteins exert their effects by modulating a variety of host innate immune responses, thereby facilitating bacterial replication and systemic infection. Salmonella enterica serovar typhimurium (S.typhimurium) is a clinically important pathogen that causes food poisoning and gastroenteritis. The SopB effector protein of S. typhimurium, encoded by Salmonella pathogenicity islands (SPI)-1 T3SS, protects host epithelial cells from infection-induced apoptosis. However, how SopB influences apoptosis induction remains unclear. Here, we investigated the mechanism of SopB action in host cells. We found that SopB inhibits infection-induced apoptosis by attenuating the production of reactive oxygen species (ROS) in mitochondria, the crucial organelles for apoptosis initiation. Further investigation revealed that SopB binds to cytosolic tumor necrosis factor receptor associated factor 6 (TRAF6) and forms a trap preventing the mitochondrial recruitment of TRAF6, an essential event for ROS generation within mitochondria. By studying the response of Traf6(+/+) and Traf6(-/-)mouse embryonic fibroblasts to S. typhimurium infection, we found that TRAF6 promoted apoptosis by increasing ROS accumulation, which led to increased Bax/Bcl-2 ratio, Bax recruitment to mitochondrial membrane, and release of Cyt c into the cytoplasm. These findings show that SopB suppresses host cell apoptosis by binding to TRAF6 and preventing mitochondrial ROS generation.
authors.affiliation: Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China. Electronic address: ruanhaihua@tjcu.edu.cn.
authors.forename: Haihua
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300192, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
authors.forename: Suying
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Hu
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300192, China. Electronic address: jianjunq@tju.edu.cn.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Qiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012480:Salmonella Infections / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000502:physiology*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; D048029:TNF Receptor-Associated Factor 6; C489224:SopB protein, Salmonella
keywords: Apoptosis; ROS; Salmonella infection; SopB; TRAF6