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

Hongxia Niu; Peng Cui; Wanliang Shi; Shuo Zhang; Jie Feng; Yong Wang; David Sullivan; Wenhong Zhang; Bingdong Zhu; Ying Zhang

doi:10.3390/antibiotics4020179

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

Antibiotics (Basel). 2015 May 12;4(2):179-87. doi: 10.3390/antibiotics4020179.

Authors

Hongxia Niu^{1

2}, Peng Cui^{3

4}, Wanliang Shi⁵, Shuo Zhang⁶, Jie Feng⁷, Yong Wang⁸, David Sullivan⁹, Wenhong Zhang⁴, Bingdong Zhu², Ying Zhang^{10

11}

Affiliations

¹ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
² Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. [email protected].
³ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
⁴ Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. [email protected].
⁵ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
⁶ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
⁷ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
⁸ Department of Clinical Microbiology Lab, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. [email protected].
⁹ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
¹⁰ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. [email protected].
¹¹ Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. [email protected].

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.

Keywords: Escherichia coli; anti-persister activity; clinical drug library; persisters; urinary tract infection.

Abstract

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