alphahemolysin

Alpha-hemolysin, also known as Hla, is a secreted pore-forming toxin produced by Staphylococcus aureus. It is a defining virulence factor of the organism and is named for its ability to produce a characteristic alpha-hemolysis on blood agar. The mature toxin is a soluble protein of about 33 kilodaltons that is released by the bacteria into the extracellular environment.

Mechanistically, alpha-hemolysin binds to host cell membranes and assembles into a heptameric pore. Monomers oligomerize on the membrane and undergo conformational changes that insert a transmembrane channel into the lipid bilayer, creating a pore roughly 1–2 nanometers in diameter. The pore disrupts cellular ion homeostasis, leading to osmotic imbalance, cell swelling, lysis, and, in some contexts, cell death.

Receptors and membrane interactions: The toxin interacts with host cell surface components to promote binding and pore formation. In multiple cell types, the ADAM10 metalloprotease has been identified as a receptor that facilitates Hla binding and cytotoxic effects. Membrane lipid composition, including cholesterol-rich domains, also influences pore formation in model systems.

Clinical relevance and research use: Alpha-hemolysin is a major contributor to tissue damage in S. aureus infections, including pneumonia, skin and soft tissue infections, endocarditis, and sepsis. Its expression is regulated by global virulence systems such as the agr quorum-sensing network. Because of its central role in disease, Hla is a target for vaccine development and antibody-based therapies aimed at neutralizing its activity. In research, Hla serves as a model for studying pore-forming toxins and host–pathogen interactions.