Multidrug Resistance and Adaptive Response to Silver and Gold Nanoparticles in Methicillin-Resistant Staphylococcus aureus from Human and Animal Sources

Antimicrobial resistance (AMR) remains a serious public health concern, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) continues to limit treatment options. This laboratory-based comparative study evaluated antibiotic resistance patterns and nanoparticle (NP) susceptibility among 110 <i>S. aureus</i> isolates recovered from human skin and soft tissue infections (<i>n</i> = 80) and camel milk (<i>n</i> = 30). Proteomic identification utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was carried out for all isolates under study. Phenotypic differentiation between MRSA and methicillin-sensitive <i>S. aureus</i> (MSSA) was performed via the cefoxitin disk diffusion method, and antimicrobial susceptibility testing was carried out using the disk diffusion method as stated in international guidelines. Multidrug resistance (MDR) was defined by established criteria. The antibacterial activity of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) was detected by broth microdilution to determine minimum inhibitory concentration values (MIC₅₀ and MIC₉₀). The ability to develop reduced susceptibility was evaluated through ten serial sub-inhibitory passages followed by stability testing without using nanoparticles. MRSA prevalence was 52.5% among human isolates and 70% among camel milk isolates. Overall, 56.4% of isolates met MDR criteria, with a significantly higher MDR rate among MRSA compared with MSSA. Both human and camel isolates showed similar resistance patterns. AgNPs exhibited strong antibacterial activity, with MIC₅₀ and MIC₉₀ values of 0.0078 mg/mL and 0.0156 mg/mL, respectively; nevertheless, AuNPs demonstrated higher MIC values. Response to NPs was similar between isolates, independent of methicillin resistance or MDR. Serial sub-inhibitory exposure resulted in increased MIC values in all tested isolates, and stable resistance persisted in 50% of cases. These results indicate ongoing MRSA circulation in human and animal settings and reinforce the need for careful and controlled use of NP-based antimicrobials.