Resurrection of antibiotics that methicillin-resistant Staphylococcus aureus resists by silver-doped bioactive glass-ceramic microparticles

This work describes a novel strategy to combat methicillin-resistant Staphylococcus aureus (MRSA) via the reactivation of inert antibiotics. This strategy exploits a multifunctional system consisting of bioactive glass-ceramic microparticles with antibacterial properties combined with various antibiotics to kill MRSA. Specifically, sol-gel derived silver-doped bioactive glass-ceramic microparticles (Ag-BG) combined with antibiotics that MRSA resists such as oxacillin or fosfomycin, significantly decreased the viability of MRSA. Ag-BG also potentiated the activity of vancomycin on static bacteria, which are typically resistant to this antibiotic. Notably, the synergistic activity is restricted to cell-envelope acting antibiotics as Ag-BG supplementation did not increase the efficacy of gentamicin. Bacteria viability assays and electron microscopy images demonstrate that Ag-BG synergizes to restore antibacterial activity to antibiotics that MRSA resists. The low cytotoxicity previously studied against oral bacteria, together with the known regenerative properties presented in previous studies, and the unique antibacterial properties observed in this work when they are combined with antibiotics, make this multifunctional system a promising approach for healing infected tissue. STATEMENT OF SIGNIFICANCE: This study addresses a very significant issue in the field of antibiotic resistance presenting an innovative way to clear MRSA, by utilizing bioactive glass-ceramic microparticles in combination with antibiotics. Multifunctional glass-ceramic microparticles doped with silver ions (Ag-BG) have been previously observed to exhibit bioactive and antibacterial properties. In this study Ag-BG microparticles were observed to synergize with antibiotics restoring their sensitivity against MRSA. This research work presents a novel approach to resurrect ineffective antibiotics and render them effective against MRSA. Cytotoxicity to eukaryotic cells is not anticipated, as it has been previously observed that these microparticles can trigger hard and soft dental tissue regeneration, when they are utilized in certain concentrations. This study opens a new avenue in the treatment of multidrug resistance bacteria.