title: Biochemical basis for activation of virulence genes by bile salts in Vibrio parahaemolyticus.
abstract: Bile salts act as a stressor to bacteria that transit the intestinal tract. Enteric pathogens have hijacked bile as an intestinal signal to regulate virulence factors. We recently demonstrated that Vibrio parahemolyticus senses bile salts via a heterodimeric receptor formed by the periplasmic domains of inner-membrane proteins VtrA and VtrC. Crystal structures of the periplasmic complex reveal that VtrA and VtrC form a β-barrel that binds bile salts in its hydrophobic interior to activate the VtrA cytoplasmic DNA-binding domain. Proteins with the same domain arrangement as VtrA and VtrC are widespread in Vibrio and related bacteria, where they are involved in regulating virulence and other unknown functions. Here we discuss our findings and review current knowledge on VtrA and VtrC homologs. We propose that signaling by these membrane-bound transcription factors can be advantageous for the regulation of membrane and secretory proteins.
authors.affiliation: a Department of Molecular Biology , University of Texas Southwestern Medical Center , Dallas , Texas , USA.|b Howard Hughes Medical Institute, University of Texas Southwestern Medical Center , Dallas , Texas , USA.
authors.forename: Giomar
authors.identifier: 0000-0002-4909-4103
authors.initials: G
authors.lastname: Rivera-Cancel
authors.affiliation: a Department of Molecular Biology , University of Texas Southwestern Medical Center , Dallas , Texas , USA.|b Howard Hughes Medical Institute, University of Texas Southwestern Medical Center , Dallas , Texas , USA.|c Department of Biochemistry , University of Texas Southwestern Medical Center , Dallas , Texas , USA.
authors.forename: Kim
authors.identifier: 0000-0002-0678-7620
authors.initials: K
authors.lastname: Orth
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D014735:Vibrio Infections / Q000378:metabolism / Q000382:microbiology*; D014736:Vibrio parahaemolyticus / Q000235:genetics* / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D037521:Virulence Factors
keywords: T3SS; T3SS2; Vibrio; Vibrio cholerae; Vibrio parahaemolyticus; bile; bile salts; intestinal pathogens; signaling; type-three secretion