Staphylococcus aureus alpha-hemolysin (Hla) (Hla)

Staphylococcus aureus alpha-hemolysin (Hla), commonly known as alpha-toxin, is a major virulence factor secreted by Staphylococcus aureus as a 33.2 kDa water-soluble monomer (UniProt P09616). The monomeric toxin targets host cells by binding to the zinc-dependent metalloprotease ADAM10, which serves as its high-affinity cellular receptor (PubMed: 20164331). Following receptor binding, seven Hla monomers assemble on the host cell membrane to form a non-lytic prepore before transitioning into a functional heptameric beta-barrel pore (PubMed: 25703521). This pore formation leads to the uncontrolled efflux of potassium and influx of calcium, resulting in cellular dysfunction, pro-inflammatory signaling, and eventual osmotic lysis (PubMed: 23935468). Hla is instrumental in the development of severe conditions such as necrotizing pneumonia, sepsis, and skin and soft tissue infections by damaging the alveolar-capillary barrier and lysing immune cells (PubMed: 26261059). Therapeutic interventions, including monoclonal antibodies like suvratoxumab and tosatoxumab, are designed to bind the Hla monomer, preventing its interaction with ADAM10 or its subsequent oligomerization, thereby neutralizing its toxic effects during active infection (PubMed: 30139813).

Other names

Alpha-toxinAlpha-hemolysinHlaHlyStaphylococcal alpha-toxin

Neutralization of the toxin by binding to the monomeric form to prevent receptor binding or oligomerization into a functional pore.