TY - JOUR
T1 - Identification of agents active against methicillin- resistant staphylococcus aureus usa300 from a clinical compound library
AU - Niu, Hongxia
AU - Yee, Rebecca
AU - Cui, Peng
AU - Tian, Lili
AU - Zhang, Shuo
AU - Shi, Wanliang
AU - Sullivan, David
AU - Zhu, Bingdong
AU - Zhang, Wenhong
AU - Zhang, Ying
N1 - Funding Information:
Acknowledgments: The work was supported in part by China Scholarship Council, Major Projects of the 12th Five-Year Plan (2013ZX10003008-003 and 2013ZX10003001-002) and 13XD1401200. YZ was supported by NIH grants AI099512 and AI108535. The following reagent was provided by the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) for distribution by BEI Resources, NIAID, NIH: Staphylococcus aureus, Strain USA300-0114, NR-46070.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/9/20
Y1 - 2017/9/20
N2 - 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.
AB - 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.
KW - Antibiotics
KW - Clinical compound library
KW - MICs
KW - MRSA
KW - Repurposed drugs
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U2 - 10.3390/pathogens6030044
DO - 10.3390/pathogens6030044
M3 - Article
C2 - 28930155
AN - SCOPUS:85032858351
SN - 2076-0817
VL - 6
JO - Pathogens
JF - Pathogens
IS - 3
M1 - 44
ER -