Genetic Requirement for ADAM10 in Severe Staphylococcus aureus Skin Infection

Staphylococcus aureus is a leading cause of human skin infections, contributing to disease in both healthy and immunocompromised individuals, also complicating burn and surgical wound sites and lesions of atopic dermatitis (Lowy, 1998; Ong and Leung, 2010). Host defense against staphylococcal skin infection is multifaceted, relying on local immunologic control through TH17 and IL-1β–driven recruitment of neutrophils in addition to the protective actions of antimicrobial peptides and physical properties of the cutaneous barrier (Miller and Cho, 2011). Pathogen virulence in staphylococcal skin infection is likewise multifactorial (Weidenmaier et al., 2010), relying in part on the action of α-hemolysin, a pore-forming cytotoxin secreted by almost all strains of S. aureus. Hla is required for dermonecrotic changes during infection, also contributing to abscess size (Kennedy et al., 2010). Immunization strategies targeting Hla protect against dermonecrosis (Kennedy et al., 2010), however the molecular mechanism by which the toxin causes pathologic disturbance of the epithelial barrier is ill-understood.