Gamma-hemolysin (Hlg)

Gamma-hemolysin is a bicomponent pore-forming toxin produced by nearly all clinical isolates of Staphylococcus aureus (UniProt P0A0E8, P0A0E9, P0A0F0). It consists of three distinct protein subunits: HlgA, HlgB, and HlgC, which combine to form two different heterooligomeric complexes, HlgA/HlgB and HlgC/HlgB (PubMed: 25135986). These toxins target host cell membranes, particularly those of erythrocytes and various leukocytes, including neutrophils and macrophages. Upon binding to specific host receptors like CXCR1, CXCR2, or C5aR1, the subunits oligomerize to form a prepore and subsequently a transmembrane beta-barrel pore, leading to cell lysis and death (PubMed: 24453252). This process contributes significantly to the pathogenesis of S. aureus infections by impairing the host's innate immune response and causing tissue damage. Therapeutic strategies focusing on gamma-hemolysin involve the development of neutralizing monoclonal antibodies, such as those found in the ASN100 cocktail, designed to prevent pore formation or block receptor binding (Aridis Pharmaceuticals).

Other names

Gamma-toxinHlgABCStaphylococcal gamma-hemolysinBicomponent leukocidin

Neutralization of toxin subunits to prevent oligomerization and pore formation on host cell membranes.