4.5 Article

Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters

期刊

ACS MEDICINAL CHEMISTRY LETTERS
卷 7, 期 5, 页码 449-453

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.5b00420

关键词

Persistence; toxin-antitoxin (TA) module; HipA (high persistence A); drug discovery

资金

  1. Ministry of Science and Technology of China [2012AA020308, 2012AA020301, 2015CB910300]
  2. National Natural Science Foundation of China [81273436]

向作者/读者索取更多资源

Persisters are a small fraction of drug-tolerant bacteria without any genotype variations. Their existence in many life-threatening infectious diseases presents a major challenge to antibiotic therapy. Persistence is highly related to toxin-antitoxin modules. HipA (high persistence A) was the first toxin found to contribute to Escherichia coli persistence. In this study, we used structure-based virtual screening for HipA inhibitors discovery and identified several novel inhibitors of HipA that remarkably reduced E. coli persistence. The most potent one decreased the persister fraction by more than five-fold with an in vitro K-D of 270 +/- 90 nM and an ex vivo EC50 of 46 +/- 2 and 28 +/- 1 mu M for ampicillin and kanamycin screening, respectively. These findings demonstrated that inhibition of toxin can reduce bacterial persistence independent of the antibiotics used and provided a framework for persistence treatment by interfering with the toxin-antitoxin modules.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据