A TSST 1 structural motif disrupts endothelial programs required for vascular regeneration.

Staphylococcus aureus causes profound vascular damage during infection, where it inflicts vascular injury across organs and generates lesions that fail to heal. Superantigens are major virulence factors in S. aureus infections, yet their direct effects on vascular repair remain unclear. We provide evidence that TSST-1 disrupts endothelial regeneration through coordinated mechanisms. TSST-1 interferes with collective directed migration, impairing endothelial cell directional persistence and preventing re-endothelialization in vitro. These defects stem from cytoskeletal disorganization, characterized by stress fiber accumulation and loss of lamellipodia, and broad suppression of motility-assoc