Melastoma malabathricum with β-lactamase inhibitory property potentiates β-lactam antibiotic against CTX-M producing Escherichia coli

Abstract Background β-lactam antibiotics are the greatest pharmaceutical development in modern medicine and are employed to treat numerous bacterial infections. Nonetheless, an alarming increase in antimicrobial resistance to β-lactam antibiotics has emerged primarily as a result of the extensive spread of β-lactamase enzymes such as extended-spectrum β-lactamases and carbapenemases, undermining the efficacy of available therapy, creating a global health problem through the rise in morbidity, mortality, and healthcare expenditure. Despite the development of β-lactamase inhibitors, the emergence of resistant β-lactamases necessitates the rapid discovery of new inhibitors or potentiators of existing antibiotics. Therefore, finding novel inhibitory compounds or a potentiator from alternative natural sources, such as medicinal plants, is imperative. Thus, this study aims to evaluate the potentiating effect of the crude extract of Melastoma malabathricum and other medicinal plants in combination with β-lactam antibiotics against resistant bacterial strains using in vitro as well as in silico study. Results The crude extract of Melastoma malabathricum was found to exhibit synergism against a CTX-M-producing E. coli when combined with cefotaxime, whose association of synergy with β-lactamase inhibition was confirmed using micro-iodometric assay and agar-based diffusion bioassay. It was further validated by molecular docking of the phytocompounds from the GC–MS study, in which 1,2-benzenedicarboxylic acid/NSC5348 exhibited the best binding energy with potential interactions with the active amino acid sites of the CTX-M. Thus, this compound was further chosen for a molecular dynamics simulation study with CTX-M-14, in which the complex was found to have good stability with consistent conformation throughout the simulation. Moreover, NSC5348 cleared drug-likeness filters. Conclusion This finding highlights the β-lactamase inhibitory potential of Melastoma malabathricum , which may also act as a potentiator of β-lactams against the CTX-M producers. Thus, Melastoma malabathricum shows promise for use in combination therapy to combat drug resistance.