title: Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.
abstract: The major Vibrio cholerae virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such as aldA, tagA, acfA, acfD, tcpI, and tarAB. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the V. cholerae cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Thomson
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA jwithey@med.wayne.edu.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Withey
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001639:Bicarbonates; D014157:Transcription Factors; C075626:tcpN protein, Vibrio cholerae