Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library.
Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library.
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DOI：
10.3390/antibiotics4020179
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发表时间：
2015-05-12
期刊：
影响因子：
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通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Niu H;Cui P;Shi W;Zhang S;Feng J;Wang Y;Sullivan D;Zhang W;Zhu B;Zhang Y
肾盂肾炎大肠大肠杆菌是尿路感染的主要原因，但目前的抗生素并不总是有效地清除持续感染。确定消除尿路致病性大肠杆菌的药物。coli persisters，我们在96孔板中使用高通量药物暴露试验筛选了由1524个化合物组成的临床药物库。通过LB平板上的生长评估细菌存活。我们确定了14种候选药物（托氟沙星、粘菌素、司帕沙星、莫西沙星和加替沙星、恩诺沙星和沙拉沙星、奥克托林、氯氟苯酚、地贝卡星、头孢菌素C、帕珠沙星、链霉素和新霉素），它们具有较高的抗持久活性。其中，妥舒沙星和粘杆菌素的抗持久力最强，能完全杀灭大肠杆菌。大肠杆菌在体外持续3天，而目前的UTI抗生素未能做到这一点。我们的研究结果可能对开发更有效的UTI治疗方法具有重要意义。
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.