Antivirulence Properties of Kuraridin Against Methicillin-Resistant Staphylococcus aureus (MRSA)

<b>Background:</b> Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a major human opportunistic pathogen that causes a wide range of infections. The vast arsenal of virulence factors expressed remains the biggest challenge in treating MRSA with conventional antibiotic therapy. <b>Methods:</b> We investigated the effects of Kuraridin at subinhibitory minimum inhibition concentrations (MICs) of 1/8, 1/16, and 1/32 (concentrations that did not inhibit bacterial growth) on adhesion to fibrinogen, adhesion, internalization into HaCaT cells, and biofilm production in three MRSA strains representing the clonal types USA300, ST30, and ST239. <b>Results:</b> All three MRSA strains exhibited a significant decrease (<i>p</i> < 0.001) in adhesion to fibrinogen upon treatment with 1/8 and 1/16 MICs of Kuraridin. The adhesion and internalization of all the MRSA strains to HaCaT cells were decreased significantly (<i>p</i> < 0.001) upon treatment with the three subinhibitory concentrations of Kuraridin. The biofilm formation of USA300 (<i>p</i> < 0.001), ST30 (<i>p</i> < 0.001), and ST239 (<i>p</i> < 0.01) was significantly reduced at a 1/8 MIC. A significant decrease in biofilm formation at a 1/16 MIC was observed for USA300 (<i>p</i> < 0.001) and ST30 (<i>p</i> < 0.05). Confocal laser scanning microscopy (CSLM) analysis of the biofilms revealed a reduction in biofilm formation in the MRSA strain when treated with Kuraridin. In the in vivo <i>Caenorhabditis elegans</i> model, Kuraridin offered a sizable degree of protection against MRSA infection without being toxic to the nematode. <b>Conclusions:</b> Our findings reveal that Kuraridin has the potential to be an alternative antivirulence option for reducing MRSA pathogenicity.