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Science. 2005 Oct 28;310(5748):670-4. Epub 2005 Oct 13.

Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization.

Author information

1
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. dhung@partners.org

Abstract

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.

PMID:
16223984
DOI:
10.1126/science.1116739
[Indexed for MEDLINE]
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