Publication Date:
2005-10-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hung, Deborah T -- Shakhnovich, Elizabeth A -- Pierson, Emily -- Mekalanos, John J -- AI26289/AI/NIAID NIH HHS/ -- K08 AI060708-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2005 Oct 28;310(5748):670-4. Epub 2005 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. dhung@partners.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16223984" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anti-Bacterial Agents/*pharmacology
;
Bacterial Proteins/biosynthesis/drug effects
;
Butyrates/*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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink