Targeting Antibiotic Resistance in Staphylococcus aureus: Screening and Docking Study of Phytochemicals as Potential Inhibitors

Abstract BACKGROUND: Staphylococcus aureus is a monoderm bacterium commonly found as part of the normal human microflora on the skin and respiratory tract. It can act as both a commensal organism and an opportunistic pathogen, causing infections in immunosuppressed individuals or after wounds or surgeries. Excessive use of selective antibiotics has led to the emergence of antibiotic-resistant strains. The aim of the study was to study the interaction of selected phytochemicals with resistance-associated proteins from penicillin-resistant (PRSA), methicillin-resistant (MRSA), and quinolone-resistant strains of S. aureus and evaluate their potential as therapeutic agents. In silico docking study of phytochemicals and standard antibiotics against key resistance proteins to identify potential candidates for combating antibiotic-resistant S. aureus infections. MATERIALS AND METHODS: Three resistance-associated proteins β-lactamase (protein data bank [PDB] ID: 3BLM) for PRSA, FemA (PDB ID: 1 LRZ) for MRSA, and GyrB (PDB ID: 9G75) were used as protein targets. A total of 28 phytochemicals from four classes (alkaloids, flavonoids, terpenoids, and essential oils) and five standard drugs (sulfamethoxazole, tetracycline, erythromycin, penicillin, and sulfadiazine) were docked against these proteins using CB-Dock and SwissDock and visualized using Discovery Studio Visualizer. No statistical analysis was performed; results are based on binding affinity scores obtained from docking studies. RESULTS: Several phytochemicals showed promising binding affinities comparable to or better than standard drugs against the selected resistance proteins. Visualizations revealed significant interactions that suggest potential inhibition of resistance mechanisms. CONCLUSIONS: The selected phytochemicals demonstrate potential as therapeutic agents against antibiotic-resistant S. aureus strains. Further experimental validation is required to explore their clinical applications.