Chitosan-coated silver nanoparticles amplify glycopeptide efficacy against Staphylococcus aureus.

The escalating prevalence of antibiotic resistance represents a critical threat to global public health, while the development of new antibiotics remains limited. Vancomycin, a glycopeptide antibiotic, is essential for treating severe Gram-positive infections. However, the emergence of vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) Staphylococcus aureus strains has raised significant concerns due to their challenging resistance profiles and limited treatment options. In this study, we developed a carboxylic acid-capped silver nanoparticle (AgNPs) platform to enhance the therapeutic delivery and efficacy of vancomycin. The nanocomposite (AgNPs/Van/CS) was engineered by leveraging electrostatic interactions between AgNPs and vancomycin, with a chitosan coating to provide stability, bacterial adhesion, and improved biocompatibility. Our results demonstrate that AgNPs/Van/CS significantly outperformed vancomycin alone, exhibiting enhanced antibacterial and antibiofilm activity against both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus strains, as well as vancomycin-intermediate (VISA) clinical isolates. Notably, AgNPs/Van/CS achieved potent bacterial inhibition at lower antibiotic concentrations and significantly reduced biofilm formation, while maintaining strong activity under diverse laboratory conditions. These findings highlight the potential of AgNPs/Van/CS as a promising strategy for managing S. aureus infections and addressing the urgent challenge of antibiotic resistance.