Document Detail


Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization.
MedLine Citation:
PMID:  16223984     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Deborah T Hung; Elizabeth A Shakhnovich; Emily Pierson; John J Mekalanos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2005-10-13
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  310     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-28     Completed Date:  2005-11-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  670-4     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. dhung@partners.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / biosynthesis,  drug effects
Butyric Acids / pharmacology*
Cell Line
Cholera / microbiology
Cholera Toxin / biosynthesis
Fimbriae, Bacterial / drug effects
Gene Expression Regulation, Bacterial / drug effects
Intestine, Small / microbiology*
Mice
Microbial Sensitivity Tests
Naphthalenes / pharmacology*
Naphthalimides
Transcription Factors / biosynthesis,  drug effects
Vibrio cholerae / drug effects*,  pathogenicity
Virulence / drug effects
Virulence Factors / biosynthesis
Grant Support
ID/Acronym/Agency:
AI26289/AI/NIAID NIH HHS; K08 AI060708-01/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bacterial Proteins; 0/Butyric Acids; 0/Naphthalenes; 0/Naphthalimides; 0/Transcription Factors; 0/Virulence Factors; 0/virstatin; 147979-50-8/tcpN protein, Vibrio cholerae; 9012-63-9/Cholera Toxin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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