Demonstration of bactericidal and synergistic activity of quercetin with meropenem among pathogenic carbapenem resistant Escherichia coli and Klebsiella pneumoniae

Abstract

Rapid dissemination of carbapenem resistant Enterobacteriaceae (CRE) is considered to be a global issue. Quercetin is a well known antimicrobial agent. Hence, it would be important to investigate bactericidal and synergistic interaction of quercetin with meropenem and elucidate effects of quercetin alone and quercetin-meropenem combination on blaNDM, blaVIM,acrB, ompC, ompF, ompk35 and ompk36 expressions, cellular morphology and cell-wall/membrane integrity. MIC, Time-kill and Baclight assays were performed to determine antibacterial/bactericidal activity of quercetin. Synergism with meropenem was evaluated by checkerboard assay followed by dose-response, isobologram analysis and FIC index, combination index calculation. Effects of meropenem, quercetin and their combinations on blaNDM, blaVIM,acrB, ompC, ompF, ompk35 and ompk36 expressions were evaluated by qRT-PCR. SEM was performed to evaluate effects of aforesaid combinations on cellular morphology. Quercetin alone exhibited at least four-fold reduced MIC value (16–256 μg/mL) than that of meropenem against CRE. It exhibited synergism with meropenem against 89.25% CRE. Again, only 128 μg/mL quercetin killed upto 99.95% bacteria within 4–6 h of dosing, which increased further to 99.99% in MIC combination of meropenem-quercetin. Thus, effective bactericidal activity of quercetin-meropenem combination might have been achieved through alteration of blaVIM, ompC expression and cellular morphology of bacteria. Quercetin exhibited bactericidal and synergistic activity with meropenem.