Synergy of Antibiotics and Antibiofilm Agents against Methicillin-Resistant Staphylococcus aureus Biofilms

Methicillin-resistant Staphylococcus aureus (MRSA) infections are some of the most common antibiotic-resistant infections, often exacerbated by the formation of biofilms. Here, we evaluated six compounds, three common antibiotics used against MRSA and three antibiofilm compounds, in nine combinations to investigate the mechanisms of synergistic eradication of MRSA biofilms. Using metabolic assessment, colony enumeration, confocal fluorescence microscopy, and scanning electron microscopy, we identified two promising combinations of antibiotics with antibiofilm agents against preformed MRSA biofilms. The broad-spectrum protease, proteinase K, and membrane-targeting antibiotic, daptomycin, worked in synergy against MRSA biofilms by manipulating the protein content, increasing access to the cell membrane of biofilm bacteria. We also found that the combination of cationic peptide, IDR-1018, with the cell wall cross-linking inhibitor, vancomycin, exhibited synergy against MRSA biofilms by causing bacterial damage and preventing repair. Our findings identify synergistic combinations of antibiotics and antibiofilm agents, providing insight into mechanisms that may be explored further for the development of effective treatments against MRSA biofilm.