Staphylococcus aureus β-hemolysin impairs macrophage phagocytosis by disrupting ruffle formation

Staphylococcus aureus , a major human pathogen, evades host immunity via multiple virulence factors. Macrophage phagocytosis is critical for clearing S. aureus to protect against infection. In this study, we demonstrated that β-hemolysin (Hlb), a sphingomyelinase (SMase), significantly impaired the phagocytic capacity of macrophages, which was strictly dependent on its SMase activity. Mechanistically, Hlb treatment significantly disrupted the formation of F-actin-rich membrane ruffles, a critical step in phagocytic uptake. Further in vivo study demonstrated that the presence of Hlb markedly increased bacterial burden. Collectively, these findings identify Hlb as a key virulence factor that subverts macrophage protection by disrupting membrane ruffle formation, thereby enhancing S. aureus survival during infection.