Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters

doi:10.1021/acsmedchemlett.5b00420

CORC > 北京大学 > 化学与分子工程学院

	Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters
	Li, Tongqing ; Yin, Ning ; Liu, Hongbo ; Pei, Jianfeng ; Lai, Luhua
刊名	ACS MEDICINAL CHEMISTRY LETTERS
	2016
关键词	Persistence toxin-antitoxin (TA) module HipA (high persistence A) drug discovery ESCHERICHIA-COLI BACTERIAL PERSISTENCE MOLECULAR-MECHANISMS CELLS
DOI	10.1021/acsmedchemlett.5b00420
英文摘要	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.; Ministry of Science and Technology of China [2012AA020308, 2012AA020301, 2015CB910300]; National Natural Science Foundation of China [81273436]; SCI(E); PubMed; ARTICLE; jfpei@pku.edu.cn; lhlai@pku.edu.cn; 5; 449-453; 7
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/433689]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Li, Tongqing,Yin, Ning,Liu, Hongbo,et al. Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters[J]. ACS MEDICINAL CHEMISTRY LETTERS,2016.
APA	Li, Tongqing,Yin, Ning,Liu, Hongbo,Pei, Jianfeng,&Lai, Luhua.(2016).Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters.ACS MEDICINAL CHEMISTRY LETTERS.
MLA	Li, Tongqing,et al."Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters".ACS MEDICINAL CHEMISTRY LETTERS (2016).