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

Area of Science:

• Microbiology
• Pharmacology
• Biochemistry

Background:

• Sortase A (SrtA) and Sortase B (SrtB) are key enzymes in Staphylococcus aureus (S. aureus) pathogenesis, mediating cell wall anchoring of virulence factors.
• Inhibition of SrtA and SrtB offers a potential therapeutic strategy to mitigate S. aureus pathogenicity, including biofilm formation, cytotoxicity, and inflammation.

Purpose of the Study:

• To investigate the inhibitory effects of the natural compound hyperin on SrtA and SrtB.
• To evaluate the efficacy of hyperin in reducing S. aureus virulence and pathogenicity in vitro and in vivo.

Main Methods:

• In silico analysis of hyperin binding to SrtA and SrtB active sites.
• In vitro assays measuring biofilm formation, bacterial adhesion, cytotoxicity, and inflammation.
• In vivo studies using Galleria mellonella infection model and a mouse pneumonia model.

Main Results:

• Hyperin effectively inhibited the transpeptidase activity of SrtA and SrtB by occupying their active pockets.
• Hyperin treatment significantly reduced S. aureus biofilm formation and adhesion to lung epithelial cells.
• Hyperin decreased S. aureus-induced cytotoxicity and inflammation without exhibiting antimicrobial or cytotoxic effects at tested concentrations.
• In vivo, hyperin alleviated tissue damage, reduced melanin formation in G. mellonella, and improved survival rates in both G. mellonella and mouse models.

Conclusions:

• Hyperin demonstrates potent inhibitory activity against S. aureus sortases, offering a novel therapeutic approach.
• Hyperin effectively mitigates S. aureus virulence factors and pathogenicity, showing promise for treating S. aureus infections.
• Hyperin is a promising natural compound for combating diseases caused by S. aureus infection.