inhibitory effect of hyperin on Staphylococcus aureus pathogenicity though interactions with sortase A and sortase B

Sortase A (SrtA) and Sortase B (SrtB) promote S. aureus adhesion by anchoring a variety of virulence proteins to the surface of the cell wall, which in turn promotes the formation of bacterial biofilms and triggers cytotoxicity and inflammation. Therefore, inhibiting the function of SrtA and SrtB to block the anchoring of virulence proteins is a promising mechanism to alleviate the pathogenicity of S. aureus. In this study, we found that a natural compound named hyperin occupied the active pockets of SrtA and SrtB and inhibited their transpeptide capacity, which resulted in a reduction in bacterial biofilm formation and the adhesion of bacteria to lung epithelial cells. Hyperin did not have antimicrobial properties or cytotoxicity at the test concentrations but decreased the cytotoxicity and inflammation of cells induced by S. aureus USA300. In vivo, hyperin significantly alleviated the tissue damage and melanin formation of infected G. mellonella (G. mellonella) and improved the survival rate of the hyperin-treated group. In a mouse pneumonia model, hyperin improved the survival rate of mice infected with S. aureus USA300, and the bacterial burden and inflammatory factor levels decreased significantly. Taken together, our results confirm that hyperin is a promising reliable natural compound for combating diseases caused by S. aureus infection.