Combating Foodborne MRSA: Identification and Silver Nanoparticle-Based Antibacterial Strategies with Antibiotic Synergy and Resistance Evolution Assessment

Ready-to-eat (RTE) foods can carry antimicrobial-resistant pathogens; however, few studies link real-world surveillance to practical interventions. This study addressed this gap by estimating the prevalence of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and methicillin-resistant <i>S. aureus</i> (MRSA) in ready-to-eat foods from Al-Qassim and evaluating a rapid, orthogonal confirmation workflow (culture → MALDI-TOF MS → Vitek 2 → <i>mecA</i>/<i>mecC</i> PCR). The in vitro activity of citrate-stabilized silver nanoparticles (AgNPs) against food-derived MRSA was quantified, and synergy with oxacillin (primary) and ciprofloxacin (secondary) was examined. Silver-susceptibility stability was assessed over 20 days of sub-MIC serial passage, with attention to whether β-lactam co-exposure constrained drift. We surveyed 149 RTE products and paired the confirmation workflow with mechanistic tests of AgNPs as antibiotic adjuvants. <i>S. aureus</i> was recovered from 24.2% of products and MRSA from 6.7%, with higher recovery from animal-source matrices and street-vendor outlets. MALDI-TOF MS provided rapid species confirmation and revealed two reproducible low-mass peaks (<i>m</i>/<i>z</i> 3990 and 4125) associated with MRSA, supporting spectral triage pending molecular confirmation. Antimicrobial susceptibility testing showed the expected β-lactam split (MRSA oxacillin/cefoxitin non-susceptible; MSSA oxacillin-susceptible but largely penicillin-resistant), with last-line agents retained. Citrate-stabilized AgNPs displayed consistent potency against food-derived MRSA (MIC 8-32 µg/mL; MIC₅₀ 16; MIC₉₀ 32) and were predominantly bactericidal (MBC/MIC ≤ 4 in 90%). Checkerboards demonstrated frequent AgNP-oxacillin synergy (median fractional inhibitory concentration index [FICI] 0.37; 4-16-fold oxacillin MIC reductions) and additive-to-synergistic effects with ciprofloxacin (median FICI 0.63), translating time-kill assays into rapid, sustained bactericidal activity without antagonism. During sub-MIC evolution, silver MICs rose modestly (median two-fold) and often regressed off drug; oxacillin co-exposure limited drift. RTE foods therefore represent credible MRSA exposure routes. Integrating MALDI-assisted triage with automated AST enables scalable surveillance, and standardized AgNP formulations emerge as promising β-lactam adjuvants-pending in situ efficacy, safety, and residue evaluation.