Journal
SCIENCE
Volume 310, Issue 5748, Pages 670-674Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1116739
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Funding
- NIAID NIH HHS [AI26289, K08 AI060708-01] Funding Source: Medline
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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.
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