Alpha-Hemolysin (Hla)

Hla is the major cytotoxic agent released by bacterium Staphylococcus aureus and the first identified member of the pore forming beta-barrel toxin family. This toxin consists mostly of beta-sheets (68%) with only about 10% alpha-helices. The hla gene on the S. aureus chromosome encodes the 293 residue protein monomer, which forms heptameric units on the cellular membrane to form a complete beta-barrel pore. This structure allows the toxin to perform its major function, development of pores in the cellular membrane, eventually causing cell death. Alpha-toxin has been shown to play a role in pathogenesis of disease, as hla knockout strains show reductions in invasiveness and virulence. Interestingly, the dosage of toxin can result in two different modes of activity. Low concentrations of toxin bind to specific, but unidentified, cell surface receptors and form the heptameric pores.