Quercetin potentiates meropenem activity among pathogenic carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii

Aims Global spread of carbapenem-resistant Pseudomonas aeruginosa (CRPsA) and Acinetobacter baumannii (CRAB) is an emerging clinical problem. Since, quercetin is a well-known antibacterial agent; it would be relevant to demonstrate synergy between quercetin and meropenem and elucidate molecular basis of effective bactericidal activity of quercetin-meropenem against CRPsA and CRAB. Methods and Results Hence, minimum inhibitory concentration (MIC), checkerboard, time-kill and Baclight assays were performed to determine the antibacterial and synergistic activity of quercetin with meropenem against CRPsA and CRAB. To corroborate synergism, fractional inhibitory concentration index, combination index calculation and isobologram analysis were performed on selected isolates. Finally, to elucidate molecular basis of effective bactericidal activity of quercetin-meropenem against CRPsA and CRAB, effect of meropenem, quercetin and their combinations on cellular morphology and levels of bla(NDM), mexB and adeB expressions were evaluated on selected isolates by scanning electron microscope and qRT-PCR. Quercetin exhibited synergy with meropenem. It inhibited bla(NDM) and AdeB expression. Half-MIC combination of quercetin-meropenem exerted bactericidal activity by disrupting cell wall/membrane integrity and altering cellular morphology. Conclusion Quercetin could potentiate meropenem activity against CRPsA and CRAB. Significance and Impact of the Study This study had demonstrated bactericidal and synergistic activity of quercetin with meropenem against CRPsA and CRAB.