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World J Microbiol Biotechnol ; 39(12): 358, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37884743

RESUMO

Staphylococcus aureus (S. aureus) induces a variety of infectious diseases in humans and animals and is responsible for hospital- and community-acquired infections. The aim of this study was to investigate how bilobetin, a natural compound, attenuates S. aureus virulence by inhibiting two key virulence factors, von Willebrand factor-binding protein (vWbp) and staphylocoagulase (Coa). The results showed that bilobetin inhibited Coa- or vWbp-induced coagulation without affecting S. aureus proliferation. The Western blotting and fluorescence quenching assays indicated that bilobetin did not affect the expression of vWbp and Coa but directly bound to the proteins with KA values of 1.66 × 104 L/mol and 1.04 × 104 L/mol, respectively. To gain further insight into the mechanism of interaction of bilobetin with these virulence factors, we performed molecular docking and point mutation assays, which indicated that the TYR-6 and TYR-18 residues on vWbp and the ALA-190 and ASP-189 residues on Coa were essential for the binding of bilobetin. In addition, the in vivo studies showed that bilobetin ameliorated lung tissue damage and inflammation caused by S. aureus, thereby improving the survival of mice. Furthermore, the use of bilobetin as an adjuvant in combination with vancomycin was more effective in the treatment of a mouse model of pneumonia. Taken together, bilobetin had a dual inhibitory effect on vWbp and Coa by reducing the virulence of S. aureus, suggesting that it is a viable lead compound against S. aureus infections.


Assuntos
Coagulase , Infecções Estafilocócicas , Humanos , Camundongos , Animais , Coagulase/genética , Coagulase/metabolismo , Coagulase/farmacologia , Proteínas de Transporte/metabolismo , Staphylococcus aureus , Virulência , Fator de von Willebrand/metabolismo , Fator de von Willebrand/farmacologia , Simulação de Acoplamento Molecular , Infecções Estafilocócicas/tratamento farmacológico , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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