title: Salmonella plasmid virulence gene spvB enhances bacterial virulence by inhibiting autophagy in a zebrafish infection model.
abstract: Salmonella enterica serovar typhimurium (S. typhimurium) is a facultative intracellular pathogen that can cause gastroenteritis and systemic infection in a wide range of hosts. Salmonella plasmid virulence gene spvB is closely related to bacterial virulence in different cells and animal models, and the encoded protein acts as an intracellular toxin required for ADP-ribosyl transferase activity. However, until now there is no report about the pathogenecity of spvB gene on zebrafish. Due to the outstanding advantages of zebrafish in analyzing bacteria-host interactions, a S. typhimurium infected zebrafish model was set up here to study the effect of spvB on autophagy and intestinal pathogenesis in vivo. We found that spvB gene could decrease the LD50 of S. typhimurium, and the strain carrying spvB promoted bacterial proliferation and aggravated the intestinal damage manifested by the narrowed intestines, fallen microvilli, blurred epithelium cell structure and infiltration of inflammatory cells. Results demonstrated the enhanced virulence induced by spvB in zebrafish. In spvB-mutant strain infected zebrafish, the levels of Lc3 turnover and Beclin1 expression increased, and the double-membraned autophagosome structures were observed, suggesting that spvB can inhibit autophagy activity. In summary, our results indicate that S. typhimurium strain containing spvB displays more virulence, triggering an increase in bacterial survival and intestine injuries by suppressing autophagy for the first time. This model provides novel insights into the role of Salmonella plasmid virulence gene in bacterial pathogenesis, and can help to further elucidate the relationship between bacteria and host immune response.
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Guang-Mei
authors.initials: GM
authors.lastname: Xu
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Niu
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: School of Biology & Basic Medical Sciences, Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, PR China. Electronic address: wushuyan@suda.edu.cn.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Wu
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D012480:Salmonella Infections / Q000382:microbiology* / Q000503:physiopathology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D037521:Virulence Factors; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid
keywords: Autophagy; Pathogenesis; Salmonella plasmid virulence gene; Zebrafish