Antimicrobial and antibiofilm activity of fungal metabolites on methicillin-resistant Staphylococcus aureus (ATCC 43300) mediated by SarA and AgrA.

Methicillin-resistant Staphylococcus aureus (MRSA) increases its antibiotic resistance by forming biofilms. Natural products (NP) or specialized metabolites have demonstrated their ability to decrease the virulence and pathogenesis of MRSA infections by inhibiting biofilm formation. The present study evaluated the antimicrobial and antibiofilm potential against MRSA of a small library of fungal NP isolated from Mexican biodiversity. The most potent antibacterial activity was observed for myrotecisin B, epiequisetin, equisetin, stachybotrolide acetate, monorden A, zearalenone, fuscin, and fusarubin. On the other hand, epifiscalin C, fiscalin C, dimethylglyotoxin, aspernolide B, and butyrolactones I and IV inhibited the biofilm formation without decreasing bacterial growth. To determine the putative mechanism of action of these compounds, docking analyses were performed against SarA and AgrA proteins, targets known to regulate biofilm production in MRSA. Overall, the results demonstrate that fungal NP may act as potential antibiofilm agents for treating MRSA infections.