Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

Journal Article · Thu Mar 04 04:00:00 EST 2010 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.0915021107· OSTI ID:1002291

Lowden, Michael J; Skorupski, Karen; Pellegrini, Maria; Chiorazzo, Michael G; Taylor, Ronald K; Kull, F Jon ^[1]

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1. Dartmouth

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 {angstrom} 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002291
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (7) ; 02, 2010 Vol. 107; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CARBOXYLIC ACIDS
CHOLERA
CRYSTAL STRUCTURE
DNA
GENES
IN VITRO
REGULATIONS
RESOLUTION
TOXINS
VIRULENCE