Identification of Agents Active against Methicillin-Resistant Staphylococcus aureus USA300 from a Clinical Compound Library
Hongxia Niu,
Rebecca Yee,
Peng Cui,
Lili Tian,
Shuo Zhang,
Wanliang Shi,
David Sullivan,
Bingdong Zhu,
Wenhong Zhang,
Ying Zhang
Affiliations
Hongxia Niu
Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
Rebecca Yee
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Peng Cui
Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
Lili Tian
Beijing Research Institute for Tuberculosis Control, Beijing 100035, China
Shuo Zhang
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Wanliang Shi
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
David Sullivan
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Bingdong Zhu
Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
Wenhong Zhang
Key Laboratory of Medical Molecular Virology, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
Ying Zhang
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat for effective treatment of several difficult-to-treat infections in humans. To identify potential new treatment options for MRSA infections, we screened a clinical compound library consisting of 1524 compounds using a growth inhibition assay in 96-well plates. We identified 34 agents which are either bacteriostatic or bactericidal against log-phase clinical MRSA strain USA300. Among them, 9 candidates (thonzonium, cetylpyridinium, trilocarban, benzododecinium, bithionol, brilliant green, chlorquinaldol, methylbenzethonium and green violet) are known antiseptics, 11 candidates are known antibiotics currently recommended for the treatment of MRSA. We identified 9 new drug candidates, 5 of which (thiostrepton, carbomycin, spiramycin, clofazimine and chloroxine) are antibiotics used for treating other infections than S. aureus infections; 4 of which (quinaldine blue, closantel, dithiazanine iodide and pyrvinium pamoate) are drugs used for treating parasitic diseases or cancer. We ranked these new drug candidates according to their MICs against the MRSA strain USA300. Our findings may have implications for more effective treatment of MRSA infections.
