title: Two regulators of Vibrio parahaemolyticus play important roles in enterotoxicity by controlling the expression of genes in the Vp-PAI region.
abstract: Vibrio parahaemolyticus is an important pathogen causing food-borne disease worldwide. An 80-kb pathogenicity island (Vp-PAI), which contains two tdh (thermostable direct hemolysin) genes and a set of genes for the type III secretion system (T3SS2), is closely related to the pathogenicity of this bacterium. However, the regulatory mechanisms of Vp-PAI's gene expression are poorly understood. Here we report that two novel ToxR-like transcriptional regulatory proteins (VtrA and VtrB) regulate the expression of the genes encoded within the Vp-PAI region, including those for TDH and T3SS2-related proteins. Expression of vtrB was under control of the VtrA, as vector-expressed vtrB was able to recover a functional protein secretory capacity for T3SS2, independent of VtrA. Moreover, these regulatory proteins were essential for T3SS2-dependent biological activities, such as in vitro cytotoxicity and in vivo enterotoxicity. Enterotoxic activities of vtrA and/or vtrB deletion strains derived from the wild-type strain were almost absent, showing fluid accumulation similar to non-infected control. Whole genome transcriptional profiling of vtrA or vtrB deletion strains revealed that the expression levels of over 60 genes were downregulated significantly in these deletion mutant strains and that such genes were almost exclusively located in the Vp-PAI region. These results strongly suggest that VtrA and VtrB are master regulators for virulence gene expression in the Vp-PAI and play critical roles in the pathogenicity of this bacterium.
authors.affiliation: Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. kodama@biken.osaka-u.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Kodama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Gotoh
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Hiyoshi
authors.forename: Mikiharu
authors.initials: M
authors.lastname: Morita
authors.forename: Kaori
authors.initials: K
authors.lastname: Izutsu
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.forename: Kwon-Sam
authors.initials: KS
authors.lastname: Park
authors.forename: Vlademir V
authors.initials: VV
authors.lastname: Cantarelli
authors.forename: Rikard
authors.initials: R
authors.lastname: Dryselius
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Honda
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005822:Genetic Vectors; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins