Alpha-hemolysin (Hla) (Hla)

Alpha-hemolysin (Hla), also known as alpha-toxin, is a potent pore-forming cytotoxin and a primary virulence factor secreted by most strains of Staphylococcus aureus (UniProt P09616). It is secreted as a 33.2 kDa water-soluble monomer that specifically binds to the host cell surface receptor ADAM10 (A Disintegrin and Metalloproteinase Domain-containing protein 10) (PubMed: 20164344). Upon binding, the monomers oligomerize into a mushroom-shaped heptameric prepore, which then inserts a beta-barrel into the host cell membrane to form a functional pore (PubMed: 8700210). This pore allows the uncontrolled efflux of ions and small molecules, leading to cellular ATP depletion, pro-inflammatory signaling, and eventually cell death via apoptosis or necrosis (PubMed: 24119669). Hla is instrumental in the pathogenesis of various conditions, including necrotizing pneumonia, skin and soft tissue infections, and sepsis, by damaging endothelial and epithelial barriers (PubMed: 22544316). Therapeutic interventions under development include monoclonal antibodies like suvratoxumab and tosatoxumab, which neutralize the toxin to prevent its interaction with host cells and mitigate tissue damage during infection (PubMed: 30139813).

Other names

Alpha-toxinStaphylococcal alpha-hemolysinHla toxinHly

Neutralization of the toxin to prevent binding to the host receptor ADAM10 and subsequent heptameric pore formation, thereby preventing cell lysis and tissue damage.