Quercetin reduces Streptococcus suis virulence by inhibiting suilysin activity and inflammation

Streptococcus suis, a globally distributed bacterial pathogen, is an important zoonotic agent for humans and animals that can lead to multiple deaths and cause major economic losses. Suilysin (SLY), secreted by most pathogenic S. suis strains, is a cytotoxic toxin that belongs to the cholesterol-dependent cytolysin family; this toxin plays a key role in a mouse meningitis model, suggesting that effective interference with the biological activity of SLY may be a potential treatment for S. suis infection. In addition, the inflammatory response induced by S. suis is an important manifestation in infections and is associated with multiple fatal diseases. In this study, we found that the natural compound quercetin can directly inhibit the pore-forming activity of SLY without affecting bacterial growth and SLY secretion at the concentrations tested in our assay. In addition, quercetin treatment significantly alleviated cytotoxicity caused by S. suis infection and effectively reduced the release of the pro-inflammatory cytokines IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) stimulated by bacteria. Significantly decreased mortality was observed for the S. suis-infected mice that received quercetin. Our results suggested that quercetin may represent a promising therapeutic candidate for S. suis infection by targeting SLY and the subsequent inflammation. The present study provides a new strategy and leading compound for S. suis infection.