Open AccessPaenipeptin Analogues Potentiate Clarithromycin and Rifampin against mcr-1 -Mediated Polymyxin-Resistant Escherichia coli In Vivo
Author(s) -
Sun Hee Moon,
Yihong Kaufmann,
En Huang
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02045-19
Subject(s) - microbiology and biotechnology , escherichia coli , clarithromycin , polymyxin , polymyxin b , antibiotics , in vivo , antimicrobial , biology , antibacterial agent , gene , biochemistry
Polymyxin resistance mediated by the mcr-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.