Abstract
Outer membrane of Gram-negative bacteria continues to be the biggest hurdle in developing new antimicrobials that target these notorious antibiotic-resistant pathogens. In this study, based on the previously identified bacterial membrane-permeabilizing effect of 7-O-pivaloxymethyl quercetin (Q-POM), we investigated bactericidal activity of various antibiotics against Gram-negative bacteria upon combination with Q-POM. Carbapenem-susceptible and resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) were evaluated for their antibacterial activity in the presence of Q-POM, which effectively sensitized both carbapenem-sensitive and resistant P. aeruginosa and A. baumannii to antibiotics. In particular, in the presence of Q-POM, the carbapenem-resistant strains, CRPA and CRAB, were sensitized to the antibiotics, and, approximately, 2–64 times decrease in MIC values were observed. Most combinations of antibiotics with Q-POM turned out to be synergistic or partially synergistic and, among those, combination of CAZ or FEP with Q-POM showed strong synergy against CRAB.
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