Quercetin 7‐O‐Glutamate Sensitizes P. aeruginosa to β‐Lactams and Vancomycin

Abstract

In this study, quercetin and its conjugates with pivaloxymethyl, glutamic acid, or alanine promoieties were evaluated for their ability to sensitize wild type P. aeruginosa to β‐lactam antibiotics. Among the quercetin conjugates, quercetin 7‐O‐glutamate was as potent as phenylalanine‐arginine β‐naphthylamide (PAβN), and addition of this conjugate (25 µg/mL) resulted in significant reduction of minimum inhibitory concentrations (MICs) of the β‐lactam antibiotics such as piperacillin, cefotaxime, and ceftazidime (two‐, four‐, and eight‐fold, respectively). Quercetin 7‐O‐glutamate was also effective in sensitizing P. aeruginosa to bulky antibiotics such as vancomycin and erythromycin through permeabilization of the outer membrane of the Gram‐negative bacterium. The outer membrane‐destabilizing activity of 7‐O‐glutamate was similar to that of PAβN, and it decreased the MICs of both vancomycin and erythromycin by 16‐fold.