title: Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. bdzhu@lzu.edu.cn.|Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. bdzhu@lzu.edu.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. zhangwenhong@fudan.edu.cn.|Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. zhangwenhong@fudan.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. wshi3@jhu.edu.
authors.forename: Wanliang
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. shuozhang66@gmail.com.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. jfeng16@jhu.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Clinical Microbiology Lab, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. sdwangyong@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. dsulliv7@jhmi.edu.
authors.forename: David
authors.initials: D
authors.lastname: Sullivan
authors.affiliation: Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. zhangwenhong@fudan.edu.cn.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. bdzhu@lzu.edu.cn.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu.|Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. yzhang@jhsph.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
keywords: Escherichia coli; anti-persister activity; clinical drug library; persisters; urinary tract infection