Unraveling the efficacy of verbascoside in thwarting MRSA pathogenicity by targeting sortase A.
Appl Microbiol Biotechnol
; 108(1): 360, 2024 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-38836914
ABSTRACT
In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide. KEY POINTS ⢠Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation. ⢠In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections. ⢠Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Infecções Estafilocócicas
/
Proteínas de Bactérias
/
Aderência Bacteriana
/
Cisteína Endopeptidases
/
Biofilmes
/
Aminoaciltransferases
/
Staphylococcus aureus Resistente à Meticilina
/
Simulação de Acoplamento Molecular
/
Glucosídeos
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article