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

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 bla(NDM), bla(VIM), 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 bla(NDM), bla(VIM), 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 mu g/mL) than that of meropenem against CRE. It exhibited synergism with meropenem against 89.25% CRE. Again, only 128 mu g/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 bla(VIM), ompC expression and cellular morphology of bacteria. Quercetin exhibited bactericidal and synergistic activity with meropenem.