Quercetin 7-O-Glutamate Sensitizes P-aeruginosa to -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 -lactam antibiotics. Among the quercetin conjugates, quercetin 7-O-glutamate was as potent as phenylalanine-arginine -naphthylamide (PAN), and addition of this conjugate (25 mu g/mL) resulted in significant reduction of minimum inhibitory concentrations (MICs) of the -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 PAN, and it decreased the MICs of both vancomycin and erythromycin by 16-fold.