Plant-mediated green synthesis of selenium nanoparticles using Schinus molle (L.) leaf extract: Antimicrobial activity against MRSA, anti-virulence properties, and anticancer potential

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) remains a critical global health concern due to its multidrug resistance, high virulence, and strong biofilm-forming capacity, necessitating the development of alternative antimicrobial strategies. In this study, selenium nanoparticles (SeNPs) were green synthesized using Schinus molle leaf extract as a natural reducing and stabilizing agent, and their antimicrobial, anti-virulence, and anticancer activities were investigated. The nanoparticles were characterized by UV–Vis, XRD, FTIR, TEM, and zeta potential analyses, while HPLC profiling of the plant extract revealed phenolic acids and flavonoids (gallic acid, catechin, chlorogenic acid, ellagic acid, caffeic acid, ferulic acid, rutin, quercetin, isorhamnetin and kaempferol) likely involved in nanoparticle formation and stabilization. The biosynthesized SeNPs were spherical (50 nm) and exhibited potent antibacterial activity against ten clinical MRSA isolates (MICs: 8–12 μg/mL). Checkerboard assays revealed strong synergistic interactions with cefoxitin, ciprofloxacin, and gentamicin (FICI ≤ 0.5), significantly reducing antibiotic MICs, while time–kill assays confirmed sustained bactericidal activity. Sub-inhibitory concentrations of the SeNPs–cefoxitin combination markedly inhibited MRSA biofilm formation, as confirmed by CLSM. Cytotoxicity assays demonstrated selective anticancer activity with minimal toxicity toward normal cells, and flow cytometry confirmed apoptosis induction in cancer cell lines. Overall, S. molle -mediated SeNPs exhibit potent antibacterial and anti-virulence effects against MRSA and enhance antibiotic efficacy, highlighting their potential as multifunctional antimicrobial adjuvants with complementary anticancer properties. • Green-synthesized SeNPs showed potent and consistent antibacterial activity against clinical MRSA isolates (MICs 8-12 μg/mL). • SeNPs displayed strong synergy with cefoxitin, ciprofloxacin, and gentamicin (FICI ≤ 0.5), reducing antibiotic MICs by up to eightfold. • Time-kill kinetics confirmed sustained, concentration-dependent inhibition over 48h at sub-MIC levels, supporting SeNPs as effective antibiotic adjuvants. • Biosynthesized SeNPs exhibited selective cytotoxic and pro-apoptotic effects in cancer cell lines