[Molecular basis for the pathogenicity of S. aureus alpha-toxins].
Staphylococcal alpha-toxin is produced by most strains of S. aureus and is considered a major pathogenic factor of these bacteria. The toxin is produced as a water-soluble molecule of MW 34000. Binding to a membrane target is accompanied by the formation of ring-structured hexamers with outer and inner diameters of 10 and 2-3 nm, respectively. The toxin rings carry lipid-binding surfaces that allow for insertion into and firm embedment within the membrane. Small transmembrane channels are thus generated that can induce a variety of pathological cellular changes. Large doses of toxin will generally cause cell lysis and death. However, sub-cytolytic toxin doses can also elicit major pathophysiological reactions. When introduced into the circulation of an isolated and perfused rabbit lung, the toxin causes steep rises in the pulmonary artery pressure, and lung edema results as a consequence of increases in vascular permeability occurring in parallel. These processes are the result of the activation of the arachidonic acid cascade by alpha-toxin in the lung. Studies using cultured endothelial cells as targets subsequently led to a hypothesis that would explain how membrane channel formation by a toxin could be linked to the observed arachidonic acid cascade activation. In essence, we propose that the toxin pores serve as non-physiological calcium channels, and that calcium influx triggers the observed reactions. It is probable that many other pathophysiological processes including inflammatory tissue reactions derive from such secondary effects of toxin action.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure; D006460:Hemolysin Proteins; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008970:Molecular Weight; D009498:Neurotoxins / Q000633:toxicity*; D011453:Prostaglandins / Q000378:metabolism; D011485:Protein Binding; D011654:Pulmonary Edema / Q000139:chemically induced; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D001095:Arachidonic Acids; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008077:Lipoproteins, LDL; D009498:Neurotoxins; D011453:Prostaglandins; C021091:staphylococcal alpha-toxin
Molekulare Grundlage für die Pathogenität des S.aureus-alpha-Toxins.