A Korean native halophyte extract attenuates the virulence of methicillin-resistant Staphylococcus aureus by inhibiting biofilm formation.

Since the COVID-19 outbreak, global attention toward infectious diseases has intensified, and many experts anticipate that the next pandemic may stem from multidrug-resistant (MDR) bacteria, often termed "Superbugs". Among them, methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most widespread MDR bacterium responsible for severe nosocomial infections. As the emergence of new resistant strains accelerates due to overuse and misuse of antibiotics, development of anti-pathogenic therapeutics has gained significant interest. In this study, we explored the anti-biofilm activity of Artemisia fukudo (Af), a halophyte abundant in bioactive metabolites. The n-butanol (n-BuOH) fraction of Af markedly inhibited MRSA biofilm formation, independent of bacterial growth inhibition or biofilm degradation. Transcriptional profiling by qRT-PCR revealed that expression of adhesion-related genes was notably downregulated. In A549 cell line infection assay, Af n-BuOH fraction treatment significantly reduced MRSA attachment and internalization. Furthermore, in a Caenorhabditis elegans infection model, Af n-BuOH fraction exposure extended host life-span, suggesting attenuation of bacterial virulence. Taken together, our findings demonstrate that Af-derived compounds interfere with initial adhesion process crucial for MRSA biofilm development and host colonization. This study highlights the therapeutic potential of halophyte-derived natural products as promising anti-virulence alternatives to conventional antibiotics for controlling infections caused by multidrug-resistant pathogens.