In Vitro and In Silico Investigations of Lepidium sativum Compounds as Promising Antibacterial Agents Against MRSA

Abstract

Staphylococcus aureus is one of the most prevalent bacterial pathogens of humans, and the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections poses significant health care challenges worldwide. MRSA often harbors a gene encoding for a specialized transpeptidase enzyme called penicillin-binding protein 2a (PBP2a), which reduces susceptibility to β-lactam antibiotics and confers resistance. To address this issue, our research aimed to identify potential natural drug candidates derived from the leaves of Lepidium sativum L. (L. sativum) using the marker protein PBP2a. Through gas chromatography/mass spectrometry analysis, we isolated five phytochemical compounds from L. sativum and subjected them to molecular docking analysis against the target bacterial protein. Two compounds (PubChem CID: 39186 and 888955) were selected for further evaluation based on their favorable docking scores (−7.1 and −6.3 kcal/mol, respectively). This computational investigation underscored the potential of these compounds as promising antibacterial candidates against the MRSA PBP2a protein. In vitro antibacterial assays using L. sativum extracts demonstrated a minimum inhibitory concentration of 15 μg/mL. Well-diffusion tests exhibited inhibition zones ranging from 12.3 ± 0.5 mm to 19 ± 0.5 mm at different concentrations, while time-kill kinetics over 24 h indicated effective bacterial growth inhibition. Statistical analysis (one-way analysis of variance) confirmed significant concentration-dependent antibacterial activity (p < 0.01). To validate the efficacy of these compounds against MRSA, further in vivo studies are strongly recommended.