Staphylococcal alpha-toxin: a study of membrane penetration and pore formation.

摘要: Cell lysis by staphylococcal alpha-toxin, a potent virulence factor of most pathogenic strains Staphylococcus aureus, follows three-step sequence: binding toxin to the membrane, leaking ions caused membrane injury, and rupturing osmotic swelling. The injury step is composed two separate events, penetration perturbation. event involves conversion soluble monomer into an amphipathic molecule, which inserts lipid bilayer membrane. perturbation association monomers, in plane form hexameric transmembrane pores. In this study, we demonstrate that, asolectin liposome system, controlling pH external buffer permits these events be temporally resolved. Using Controlled-Pore Glass bead-purified four are measured as function pH: (a) release potassium from prelabeled vesicles, (b) globally hydrophobic (c) detergent toxin, (d) labeling with photoactivable, radiolabeled, probes. Two net state, paired for occur, each requires 4.6 or less. contrast, photolabeling probes PC I II (where represents phosphatidylcholine) easily detectable at values high 5.0 6.0. These results lowered, distinct changes physical properties alpha-toxin occur. first, occurs under mild acidic conditions, converts water-soluble molecule molecule. second, requiring relatively more Correlated acquisition new biological properties. conformation correlates property reversible evidenced photoactivable At lower pH, causing damage cell internal ions, presumably formation hexamer pores.(ABSTRACT TRUNCATED AT 400 WORDS)