Affiliation:
1. Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
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
.
Publisher
American Association for the Advancement of Science (AAAS)
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3. Materials and methods are available as supporting material on Science Online.
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