title: The orphan response regulator CovR: a globally negative modulator of virulence in Streptococcus suis serotype 2.
abstract: Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. However, the pathogenesis of S. suis serotype 2 infection is not well understood. In this study, we report that an orphan response regulator, CovR, globally regulates gene expression and negatively controls the virulence of S. suis 05ZYH33, a streptococcal toxic shock syndrome (STSS)-causing strain. A covR-defective (DeltacovR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the DeltacovR mutant to epithelial cells was greatly increased, and its resistance to phagocytosis and killing by neutrophils and monocytes was also significantly enhanced. More importantly, inactivation of covR increased the lethality of S. suis serotype 2 in experimental infection of piglets, and this phenotype was restored by covR complementation. Colonization experiments also showed that the DeltacovR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the DeltacovR mutant is in full agreement with the large number of genes controlled by CovR as revealed by transcription profile analysis: 2 genes are positively regulated, and 193 are repressed, including many that encode known or putative virulence factors. These findings suggested that CovR is a global repressor in virulence regulation of STSS-causing S. suis serotype 2.
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Pan
authors.forename: Junchao
authors.initials: J
authors.lastname: Ge
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Youjun
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Ji
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Peiju
authors.initials: P
authors.lastname: Shi
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Feng
authors.forename: Xina
authors.initials: X
authors.lastname: Hao
authors.forename: Ruiping
authors.initials: R
authors.lastname: Dong
authors.forename: Fuquan
authors.initials: F
authors.lastname: Hu
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006461:Hemolysis; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D017011:Streptococcus suis / Q000472:pathogenicity / Q000502:physiology*; D016019:Survival Analysis; D013552:Swine; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins