Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization
Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization
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DOI：
10.1126/science.1116739
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发表时间：
2005-10-28
期刊：
影响因子：
56.9
通讯作者：
Mekalanos, JJ
中科院分区：
文献类型：
--
作者：
Hung, DT;Shakhnovich, EA;Mekalanos, JJ
抗生素耐药性的增加需要开发新的方法来对抗感染。毒力基因在体内的表达代表了尚未探索的抗生素发现的靶点。一个高通量，表型筛选被用来确定一个小分子4-[N-（1，8-萘二甲酰亚胺）]-正丁酸，virstatin，抑制霍乱弧菌的毒力调节。通过抑制转录调节因子ToxT，virstatin阻止两个关键的霍乱弧菌毒力因子，霍乱毒素和毒素共调节的表达。菌毛口服给药。的virstatin保护幼鼠免受霍乱弧菌的肠道定植。
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.