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 AraC-family regulator, ToxT. We have solved the 1.9 A 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, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that cis-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.
Lowden
Michael J
MJ
Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, NH 03755, USA.
Skorupski
Karen
K
Pellegrini
Maria
M
Chiorazzo
Michael G
MG
Taylor
Ronald K
RK
Kull
F Jon
FJ
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D003460:Crystallization; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D015151:Immunoblotting; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014734:Vibrio cholerae / Q000737:chemistry*
D001426:Bacterial Proteins; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D014157:Transcription Factors; C075626:tcpN protein, Vibrio cholerae; C008757:palmitoleic acid; D004247:DNA