title: A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters.
abstract: To identify effective compounds that are active against Staphylococcus aureus (S. aureus) persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.
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. ryee2@jhu.edu.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Yee
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 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
keywords: Staphylococcus aureus; clinafloxacin; clinical drug library; persisters; tosufloxacin