Staphylococcus aureus intoxicates stem cells to accelerate repair

Pathogens are typically viewed as barriers to healing—but Staphylococcus aureus defies this paradigm. We identify its secreted toxin LukED as an unexpected accelerator of tissue repair. Through functional screening and bacterial genetics, we uncover LukED as a pro-repair virulence factor that enhances both epithelial and muscle healing. In skin, LukED drives migratory and senescence-associated programs in wound-edge epidermal stem and progenitor cells. Using organoid models and primary epithelial cultures, we show that LukED acts directly on skin epithelia to promote repair. Remarkably, this activity is independent of pore formation, revealing a noncanonical function for an otherwise cytolytic toxin. Our findings redefine microbial influence on host physiology and introduce microbial DAMPs (mDAMPs) as a new class of pro-reparative effectors. Overall design: RNA-seq of murine skin wound edge tissue at D1 post-wounding. At D0, wounds were associated with PBS or S. aureus LAC (1000 CFU).