title: Staphylococcus aureus alpha-toxin. Dual mechanism of binding to target cells.
abstract: Staphylococcal alpha-toxin was radiolabeled to high specific radioactivity (1,500-3,000 Ci/mmol) under retention of its hemolytic activity. Binding studies with susceptible rabbit erythrocytes and highly resistant human erythrocytes revealed that binding of alpha-toxin to target cells can occur via two different mechanisms. Binding of alpha-toxin to rabbit erythrocytes initially involves specific binding sites and occurs at low concentrations, with half-maximal binding at 1-2 nM. In contrast, toxin binding to human erythrocytes is absorptive and nonspecific, in this case, significant binding as well as hemolysis occur only at alpha-toxin concentrations exceeding 1 microM. Autoradiographic analyses of membrane-associated alpha-toxin from either cell species proved that hemolysis was inevitably associated with the formation of toxin hexamers. Our data indicate that the high susceptibility of certain target cells toward alpha-toxin is caused by the presence of specific binding sites. However, membrane damage of both susceptible and nonsusceptible target cells occurs via a common mechanism involving toxin oligomerization and pore formation.
authors.affiliation: La Jolla Cancer Research Foundation, Cancer Research Center, California 92037.
authors.forename: A
authors.initials: A
authors.lastname: Hildebrand
authors.forename: M
authors.initials: M
authors.lastname: Pohl
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D011817:Rabbits; D013211:Staphylococcus aureus / Q000378:metabolism*; D013696:Temperature
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin