Corilagin alleviates Staphylococcus aureus pathogenicity by interacting with amidase and α-hemolysin.

Staphylococcus aureus amidase cleaves the peptidoglycan that connect parent and offspring to promote bacterial proliferation, and it also affects the formation of bacterial biofilm. The critical roles of α-hemolysin (Hla) in the pathogenicity of S. aureus are indispensable. Compounds that inhibit the functions of these two proteins can provide a new strategy and a promising agent for the development of S. aureus infection inhibitors. In this study, it was found that corilagin bound to the active pocket of amidase and interacted with His370, Glu324, His382 and Ala288, the binding inhibited the function of amiA to hydrolyze peptidoglycan and resulted in slower bacterial growth and fewer biofilm formation. Additionally, corilagin inhibited the hemolytic activity of USA300 cultural supernatants by reducing Hla production. It also suppressed the function of purified Hla by binding to the rim region, Arg200, Gln194, Tyr182, Trp179 and Asn176 were identified as the critical residues for their interaction. At the cellular level, corilagin reduced the cytotoxicity and adhesion of USA300 to mouse macrophage cells and human lung cancer epithelial cells. In the USA300 mouse pneumonia model, corilagin reduces the colonization of bacteria in lung tissue, alleviates edema and inflammatory responses, and improves the survival percentage of the infected mice. The survival of G. mellonella that treated with USA300 and corilagin was higher than the samples from USA300 and ampicillin treatment group. Collectively, These results provide a basis for corilagin used as an anti-S. aureus infection agent.