Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization

被引：284

作者：

Hung, DT ^{[1
]}

Shakhnovich, EA ^{[1
]}

Pierson, E ^{[1
]}

Mekalanos, JJ ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA

来源：

SCIENCE | 2005年 / 310卷 / 5748期

关键词：

D O I：

10.1126/science.1116739

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：670 / 674

页数：5

共 19 条

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