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Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library

机译：从临床药物库中鉴定抗致病性大肠杆菌的抗Persister活性

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Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine, clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin), which had high anti-persister activity. Among them, tosufloxacin and colistin had the highest anti-persister activity and could completely eradicate E. coli persisters in 3 days in vitro while the current UTI antibiotics failed to do so. Our findings may have implications for the development of a more effective treatment for UTIs.
机译：致病性大肠杆菌是尿路感染（UTI）的主要原因，但是目前的抗生素并不总是能有效清除持续性感染。为了鉴定消除尿路致病性大肠杆菌残留的药物，我们在96孔板上使用高通量药物暴露试验筛选了由1524种化合物组成的临床药物文库。通过在LB平板上的生长来评估细菌存活率。我们确定了14种候选药物（托舒沙星，大肠菌素，司帕沙星，莫西沙星和加替沙星，恩诺沙星和沙拉沙星，八度碱，氯氟辛醇，地贝卡星，头孢菌素C，帕唑沙星，链霉素和新霉素），它们具有很高的抗perperpers活性。其中，tosufloxacin和粘菌素具有最高的抗-杀虫剂活性，可以在3天的时间内彻底清除大肠杆菌中的持久性，而目前的UTI抗生素未能做到。我们的发现可能对开发更有效的尿路感染治疗有影响。

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