Peng Cui: Key Laboratory of Molecular Virology, Institute of Medical Microbiology, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Hongxia Niu: Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology and Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Wanliang Shi: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Shuo Zhang: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Hao Zhang: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Joseph Margolick: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Wenhong Zhang: Key Laboratory of Molecular Virology, Institute of Medical Microbiology, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China zhangwenhong@fudan.edu.cn yzhang@jhsph.edu.
Ying Zhang: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA zhangwenhong@fudan.edu.cn yzhang@jhsph.edu.
Persisters are small populations of quiescent bacterial cells that survive exposure to bactericidal antibiotics and are responsible for many persistent infections and posttreatment relapses. However, little is known about how to effectively kill persister bacteria. In the work presented here, we found that colistin, a membrane-active antibiotic, was highly active against Escherichia coli persisters at high concentrations (25 or 50 μg/ml). At a clinically relevant lower concentration (10 μg/ml), colistin alone had no apparent effect on E. coli persisters. In combination with other drugs, this concentration of colistin enhanced the antipersister activity of gentamicin and ofloxacin but not that of ampicillin, nitrofurans, and sulfa drugs in vitro The colistin enhancement effect was most likely due to increased uptake of the other antibiotics, as demonstrated by increased accumulation of fluorescence-labeled gentamicin. Interestingly, colistin significantly enhanced the activity of ofloxacin and nitrofurantoin but not that of gentamicin or sulfa drugs in the murine model of urinary tract infection. Our findings suggest that targeting bacterial membranes is a valuable approach to eradicating persisters and should have implications for more effective treatment of persistent bacterial infections.
References
Clin Infect Dis. 2011 Mar 1;52(5):e103-20
[PMID: 21292654]
