期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 4, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02045-19
关键词
lipopeptide; paenipeptin; mcr-1; potentiator; combination therapy
资金
- National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) award [R21AI146693]
- Center for Microbial Pathogenesis and Host Inflammatory Responses through the Center of Biomedical Research Excellence Award from National Institute of General Medical Sciences (NIH/NIGMS). [P20GM103625]
- Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000
Polymyxin resistance mediated by the rncr-1 gene threatens the last-resort antibiotics. Linear lipopeptide paenipeptin analogues 1 and 15 disrupted the outer membrane of Gram-negative pathogens and potentiated clarithromycin and rifampin against mcr-1-positive Escherichia coli from the FDA-CDC Antimicrobial Resistance Isolate Bank. In the presence of paenipeptin, clarithromycin and rifampin resulted in over 3-log reduction of E. coli in vitro. Moreover, paenipeptin-antibiotic combinations significantly reduced E. coli in a murine thigh infection model.
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