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Originally published in Science Express on 13 October 2005
Science 28 October 2005:
Vol. 310. no. 5748, pp. 670 - 674
DOI: 10.1126/science.1116739
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Reports

Small-Molecule Inhibitor of Vibrio cholerae Virulence and Intestinal Colonization

Deborah T. Hung,* Elizabeth A. Shakhnovich, Emily Pierson, John J. Mekalanos

Increasing antibiotic resistance requires the development of new approaches to combating infection. Virulence gene expression in vivo represents a target for antibiotic discovery that has not yet been explored. A high-throughput, phenotypic screen was used to identify a small molecule 4-[N-(1,8-naphthalimide)]-n-butyric acid, virstatin, that inhibits virulence regulation in Vibrio cholerae. By inhibiting the transcriptional regulator ToxT, virstatin prevents expression of two critical V. cholerae virulence factors, cholera toxin and the toxin coregulated pilus. Orogastric administration of virstatin protects infant mice from intestinal colonization by V. cholerae.

Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: dhung{at}partners.org

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