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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 7; pp. 2860 - 2865
• Main Authors: Lowden, Michael J., Skorupski, Karen, Pellegrini, Maria, Chiorazzo, Michael G., Taylor, Ronald K., Kull, F. Jon, Mekalanos, John J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16-02-2010; National Acad Sciences
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Base Sequence; Bile acids; Binding sites; Biological Sciences; CARBOXYLIC ACIDS; CHOLERA; CRYSTAL STRUCTURE; Crystallization; Deoxyribonucleic acid; DNA; DNA - metabolism; Electrophoretic Mobility Shift Assay; Fatty acids; Fatty Acids - metabolism; Fatty Acids, Monounsaturated - metabolism; Gene expression; Gene expression regulation; Gene Expression Regulation, Bacterial - genetics; GENES; Immunoblotting; IN VITRO; Magnetic Resonance Spectroscopy; MATERIALS SCIENCE; Models, Molecular; Molecular Sequence Data; Monomers; Monounsaturated fatty acids; Nonesterified fatty acids; Protein Structure, Tertiary - genetics; REGULATIONS; RESOLUTION; TOXINS; Transcription Factors - chemistry; Transcription Factors - metabolism; Vibrio cholerae; Vibrio cholerae - chemistry; Virology; VIRULENCE
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0915021107

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.