Toxin and Virulence Regulation inVibrio cholerae

Of the more than 200 different serogroups of Vibrio cholerae that have been isolated, only two of these, O1 and O139, have been found to have epidemic and pandemic potential. CTXφ carries the genes for CT (ctxA and ctxB) and the VPI contains the genes (tcpA-E and tcpJ) responsible for the synthesis and assembly of the essential colonization factor toxin-coregulated pilus (TCP). As part of the acetoin operon, AphA represses the expression of two PhoB-activated genes, acgA and acgB, that encode proteins which influence motility and biofilm formation by altering c-di-GMP levels in the cell. Bicarbonate may be an important in vivo signal that increases the activity of ToxT during infection and induces virulence gene expression. Once V. cholerae has disseminated out of the host and virulence gene expression is no longer required, TcpP and ToxT levels are decreased by proteolysis and H-NS reestablishes repression at the various promoters. Thus, like GbpA, FrhA plays an important role in V. cholerae in both the host and in the aquatic environment. A model for V. cholerae infection involves motile bacteria attaching to the intestinal cell surface, after which they upregulate virulence factor expression and downregulate motility. The flagellar regulatory hierarchy also influences virulence gene expression in V. cholerae through the quorum sensing system. Recent advances in the development of cDNA sequencing (RNA-seq) have facilitated the generation of comprehensive transcriptome profiles of V. cholerae during infection in both the rabbit and mouse models of cholera.