Antioxidant-based synergistic eradication of methicillin-resistant Staphylococcus aureus (MRSA) biofilms with bacitracin

Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) have serious clinical implications. However, it is difficult to eradicate MRSA biofilms due to the increased tolerance to antimicrobials of biofilms. In this study, we investigated the synergistic anti-biofilm effect of the combination of octyl gallate (OG), an antioxidant approved by the US Food and Drug Administration (FDA) as a food additive, and bacitracin, an antimicrobial peptide commonly used in topical antimicrobial ointments. The results of biofilm assays showed that OG enabled bacitracin at concentrations as low as 10 ⁻³ U/ml to inhibit biofilm formation in MRSA. A confocal microscopic analysis exhibited that the combination of bacitracin and OG suppressed biofilm formation in MRSA highly effectively compared to the single treatment of either bacitracin or OG. The synergistic anti-biofilm activity of bacitracin and OG was also confirmed in MRSA strains from humans, including USA300, which is the predominant clone of community-associated MRSA in the US. To the best of our knowledge, this is the first report about the synergistic anti-biofilm activity of an antimicrobial peptide and an antioxidant against MRSA.