文献类型：期刊文献

英文题名：S-nitrosylation-mediated activation of a histidine kinase represses the type 3 secretion system and promotes virulence of an enteric pathogen

作者：Gu, Dan[1,2];Zhang, Yibei[1,3];Wang, Qiyao[3];Zhou, Xiaohui[1]

机构：[1]Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA;[2]Yangzhou Univ, Coll Biosci & Biotechnol, Yangzhou, Jiangsu, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2020

卷号：11

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000594648000013)】；

基金：This work was supported partially by US Department of Agriculture Grant CONS00935 and fund provided by the University of Connecticut. We gratefully acknowledge the quantitative proteomics analysis conducted by Dr. Jeremy L. Balsbaugh, Director of the Proteomics & Metabolomics Facility, a component of the Center for Open Research Resources and Equipment at the University of Connecticut.

语种：英文

摘要：Vibrio parahaemolyticus is the leading cause of seafood-borne diarrheal diseases. Experimental overproduction of a type 3 secretion system (T3SS1) in this pathogen leads to decreased intestinal colonization, which suggests that T3SS1 repression is required for maximal virulence. However, the mechanisms by which T3SS1 is repressed in vivo are unclear. Here, we show that host-derived nitrite modifies the activity of a bacterial histidine kinase and mediates T3SS1 repression. More specifically, nitrite activates histidine kinase sensor VbrK through S-nitrosylation on cysteine 86, which results in downregulation of the entire T3SS1 operon through repression of its positive regulator exsC. Replacement of cysteine 86 with a serine (VbrK C86S mutant) leads to increased expression of inflammatory cytokines in infected Caco-2 cells. In an infant rabbit model of infection, the VbrK C86S mutant induces a stronger inflammatory response at the early stage of infection, and displays reduced intestinal colonization and virulence at the later stage of infection, in comparison with the parent strain. Our results indicate that the pathogen V. parahaemolyticus perceives nitrite as a host-derived signal and responds by downregulating a proinflammatory factor (T3SS1), thus enhancing intestinal colonization and virulence.Vibrio parahaemolyticus causes seafood-borne diarrheal diseases. Here, the authors show that the pathogen uses a histidine kinase to sense host-derived nitrite and downregulate a proinflammatory type 3 secretion system, thus enhancing intestinal colonization and virulence.