Quercetin‐Pivaloxymethyl Conjugate Potentiates Antibiotics against Pseudomonas aeruginosa and Acinetobacter baumannii

[摘要] 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.

[学科分类] 化学（综合）

[关键词] Multidrug resistance;Gram‐negative;Inhibition;Quercetin conjugate