Biogenic Selenium Nanoparticles from Lactiplantibacillus plantarum as a Potent Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus

<b>Background:</b> Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) remains a major global health concern owing to its multidrug resistance and persistence despite continued antibiotic development. Eco-friendly nanomaterials such as selenium nanoparticles (SeNPs) have emerged as promising antimicrobial alternatives because of their high biocompatibility and lower toxicity compared to conventional metallic nanoparticles. In this study, we investigated the inhibitory effects and underlying mechanisms of <i>Lactiplantibacillus plantarum</i> (LP)-derived SeNPs (LP-SeNPs) on MRSA. <b>Methods:</b> SeNPs were biosynthesized using the antibacterial cell-free supernatant (CFS) of LP, which provides naturally reducing and stabilizing biomolecules. The resulting LP-SeNPs were characterized by physicochemical and structural analyses and compared to chemically synthesized SeNPs (Chem-SeNPs). Antibacterial activity was assessed through minimum inhibitory concentration (MIC) testing, time-kill kinetics, and cell viability assays. <b>Results:</b> LP-SeNPs, which were spherical with an average diameter of 107 nm, exhibited selective antibacterial activity against Gram-positive bacteria and showed no effect on Gram-negative strains. Notably, all six MRSA isolates demonstrated high susceptibility, with MIC values approximately 100-fold lower than that of <i>S. aureus</i> ATCC 25923, a non-MRSA reference strain. LP-SeNPs were also non-cytotoxic up to 20-fold the MIC (IC₅₀ > 10 µg/mL). Mechanistic analyses indicated that disruption of the bacterial cell membrane was the primary antibacterial mechanism, supported by additional contributions from reactive oxygen species generation and protein synthesis inhibition. <b>Conclusions:</b> LP-SeNPs represent a sustainable, biocompatible, and potent antibacterial nanoplatform with strong selectivity for Gram-positive pathogens, particularly MRSA. These findings highlight their potential as eco-friendly and targeted therapeutic strategies for combating MRSA infections.