Inhibitory effect of bilobalide on Staphylococcus aureus von Willebrand factor-binding protein and its therapeutic effect in mice with pneumonia.
J Appl Microbiol
; 134(10)2023 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-37833234
ABSTRACT
AIMS:
Disabling bacterial virulence with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The von Willebrand factor-binding protein of Staphylococcus aureus was identified previously as a key virulence determinant. Our objective was to discover a von Willebrand-factor binding protein (vWbp) inhibitor distinct from the antibiotics used to prevent infections resulting from S. aureus. METHODS ANDRESULTS:
Using coagulation assays, we found that the sesquiterpene trilactone bilobalide blocks coagulation mediated by vWbp, but has no impact on the growth of S. aureus at a concentration of 128 µg ml-1. Moreover, a mouse model of pneumonia caused by S. aureus indicated that bilobalide could attenuate S. aureus virulence in vivo. This effect is achieved not by interfering with the expression of vWbp but by binding to vWbp, as demonstrated by western blotting, thermal shift assays, and fluorescence quenching assays. Using molecular dynamic simulations and point mutagenesis analysis, we identified that the Q17A and R453A residues are key residues for the binding of bilobalide to vWbp.CONCLUSIONS:
Overall, we tested the ability of bilobalide to inhibit S. aureus infections by targeting vWbp and explored the potential mechanism of this activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Infecções Estafilocócicas
/
Bilobalídeos
Limite:
Animals
Idioma:
En
Revista:
J Appl Microbiol
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China