raw data

Staphylococcus aureus （S. aureus）, more specifically methicillin-resistant Staphylococcus aureus (MRSA), is a bacterial pathogen that poses a serious threat to human health. MRSA exhibits a high degree of resistance and multiple virulence factors, especially the formation of biofilm that increasingly complicate treatment. Therefore, it is essential to develop novel antimicrobials. Here we investigated artesunate (ART), a sesquiterpene lactone extracted from Artemisia annua, as an antivirulence agent and antimicrobial sensitizer of S. aureus. In this study, it was showed that ART significantly reduced biofilm formation by S. aureus at sub-minimal inhibitory concentrations (MICs) through the inhibition of polysaccharide intercellular adhesin (PIA) production, without affecting bacterial growth. Molecular docking indicated that the down-regulated icaA gene identified in qRT-PCR may be the target of ART. Moreover, evidence was brought that ART reduced hemolysin, lipase, and nuclease activities and attenuated S. aureus infections in Galleria mellonella models. Notably, checkerboard assays showed that the combination of ART with erythromycin, gentamicin, and vancomycin can exert synergistic effects on S. aureus. Low concentrations of ART were sufficient to sensitize erythromycin-resistant strains of S. aureus, such as the Newman strain. This study highlighted the antibiofilm and antivirulence potential of ART against S. aureus, and brought evidence that it may act as an antimicrobial sensitizer to avoid the development of multidrug-resistant bacteria. In conclusion, ART is a safe and effective antibiotic adjuvant against S. aureus infection.