Reversing bacterial resistance to antibiotics: Exploring natural elements and plant-derived metallo-βeta-lactamase inhibitors

Objectives: Carbapenem resistance driven by metallo-β-lactamase (MBL) production represents a major limitation in the treatment of urinary tract infections (UTIs) caused by extensively drug-resistant (XDR) bacteria. The present study aimed to investigate the inhibitory effect of selected medicinal plant extracts on MBL activity and to assess their potential to enhance or partially restore the in vitro activity of meropenem against XDR uropathogenic isolates.Materials and Methods: Six carbapenem-resistant clinical isolates of Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were phenotypically screened using the Double Disc Synergy Test (DDST) and Modified Carba-NP test, followed by molecular detection of MBL-associated genes. MBL inhibition was assessed using a modified Fe(III)–o-phenanthroline assay at graded extract concentrations. Restoration of meropenem activity was evaluated by modified DDST, and minimum bactericidal concentration (MBC) were determined for effective combinations. Statistical analysis was performed using one-way ANOVA.Results: All isolates were confirmed as MBL producers phenotypically and genetically, with frequent detection of blaNDM. Several plant extracts demonstrated concentration-dependent MBL inhibition, with Cymbopogon citratus showing the strongest effect. Selected extracts significantly enhanced meropenem activity in disc-based assays, increasing inhibition zones from baseline resistance levels. Effective combinations exhibited bactericidal activity at defined concentrations.Conclusion: Selected medicinal plant extracts, particularly Cymbopogon citratus, exhibit in vitro MBL inhibitory activity and can partially restore meropenem efficacy against XDR uropathogens, supporting their potential role as resistance-modifying adjuvants.