Structure of Vibrio cholerae ToxT Reveals a Mechanism for Fatty Acid Regulation of Virulence Genes

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraCfamily regulator, ToxT. We have solved the 1.9 Å resolution crystal structure of ToxT, which reveals folds in the N-and C-terminal domains that share a number of features in common with AraC, Mar A, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, c/s-palmitoleate. The finding that c/s-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.