INTEGRATED COMPUTATIONAL AND EXPERIMENTAL EVALUATION OF ALLICIN AS A NATURAL INHIBITOR OF PENICILLIN-BINDING PROTEINS IN METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS

Abstract

Context Antimicrobial resistance is a major global health challenge that contributes to treatment failure and increased mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is an important multidrug-resistant pathogen associated with severe infections and bacteremia, with mortality rates ranging from 30% to 40%. MRSA produces several virulence factors, including staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), leukocidins, hemolysins, and exfoliative toxins, which contribute to its pathogenicity. Garlic (Allium sativum) contains bioactive compounds such as allicin, flavonoids, saponins, and tannins that exhibit antibacterial activity. Allicin (diallyl thiosulfinate), generated from alliin by the enzyme alliinase in the presence of water, possesses broad-spectrum antimicrobial activity against several drug-resistant bacteria. One mechanism of β-lactam resistance in MRSA involves alterations in penicillin-binding proteins (PBPs), resulting in reduced antibiotic affinity. In the present study, allicin was evaluated as a potential inhibitor of penicillin-binding protein 3 (PBP3) of Staphylococcus aureus using molecular docking analysis. The results demonstrated favorable binding interactions between allicin and PBP3, suggesting its potential as an alternative therapeutic candidate against MRSA infections. Methods: The three-dimensional structure of PBP3 of Staphylococcus aureus was obtained from the Protein Data Bank, while the structure of allicin was retrieved from the PubChem database. Molecular docking was performed to predict the binding affinity and interaction pattern of allicin with PBP3. Protein–ligand interactions and docking scores were analyzed to evaluate the inhibitory potential of allicin against MRSA.