Targeting penicillin binding protein 2a in methicillin resistant Staphylococcus aureus using selected phytocompounds: an environmental surveillance and in silico molecular docking study

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat owing to its resistance to beta-lactam antibiotics and persistence in diverse environments. Harvested rainwater, widely used for household purposes in Nigerian communities, represents an understudied potential reservoir for antimicrobial-resistant organisms. This study had two linked objectives: to investigate the occurrence of mecA -positive S. aureus in household harvested rainwater from Oregbeni Community, Ikpoba-Okha Local Government Area, Benin City, Nigeria, and to conduct an in silico molecular docking analysis of selected phytocompounds against penicillin-binding protein 2a (PBP2a) as a hypothesis-generating step toward identifying candidate PBP2a inhibitors. Thirty household rainwater samples were collected from randomly selected zinc-roofed households during the rainy season and analyzed by culture-based, biochemical, and molecular methods. Nineteen presumptive S. aureus isolates were recovered and confirmed by PCR amplification of the nuc gene; 8 of these 19 isolates (42.1%) harbored the mecA gene, indicating the presence of methicillin resistance determinants. Molecular docking of 25 phytocompounds against PBP2a (PDB: 5M18) using AutoDock Vina identified epigallocatechin gallate (−8.1 kcal/mol), luteolin (−7.3 kcal/mol), andrographolide (−7.2 kcal/mol), and apigenin (−7.1 kcal/mol) as priority compounds. These findings are strictly preliminary; experimental validation through molecular dynamics simulations, enzyme inhibition assays, and in vitro antibacterial testing is required before any conclusions on anti-MRSA efficacy can be drawn. The study underscores the need for improved microbiological surveillance of harvested rainwater and provides a structural basis for prioritizing phytocompounds for future experimental investigation.