Retention of methicillin susceptibility in Staphylococcus aureus using natural adjuvant as an allosteric modifier of penicillin-binding protein 2a

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global public health challenge due to its resistance to conventional antibiotics, primarily mediated by the mutated penicillin-binding protein, PBP2a. This study aims to investigate the potential of phytochemicals derived from medicinal plants in the Indian subcontinent to serve as adjuvants, enhancing the efficacy of methicillin against MRSA through allosteric modification of PBP2a using molecular docking and molecular dynamics (MD) simulation. After comprehensive Absorption, Distribution, Metabolism, and Excretion (ADME) profiling, along with AMES and hepatotoxicity tests, 9 compounds were shortlisted as suitable adjuvant candidates. Among them, nimbolide, quercetin, emodin, daidzein, eriodictyol, luteolin, and apigenin exhibited strong binding affinity to the allosteric site of PBP2a, with docking scores ranging from -8.7 to…