title: Generation of a membrane-bound, oligomerized pre-pore complex is necessary for pore formation by Clostridium septicum alpha toxin.
abstract: Low-temperature inhibition of the cytolytic activity of alpha toxin has facilitated the identification of an important step in the cytolytic mechanism of this toxin. When alpha toxin-dependent haemolysis was measured on erythrocytes at various temperatures it was clear that at temperatures < or = 15 degrees C the haemolysis rate was significantly inhibited with little or no haemolysis occurring at 4 degrees C. Alpha toxin appeared to bind to and oligomerize on erythrocyte membranes with similar kinetics at 4 degrees C and 37 degrees C. The slight differences in these two processes at 4 degrees C and 37 degrees C could not account for the loss of cytolytic activity at low temperature. At 4 degrees C alpha toxin neither stimulated potassium release from erythrocytes nor formed pores in planar membranes. In contrast, at temperatures > or = 25 degrees C both processes proceeded rapidly. Pores that were opened in osmotically stabilized erythrocytes could not be closed by low temperature. Therefore, low temperature appeared to prevent the oligomerized complex from forming a pore in the membrane. These data support the hypothesis that alpha toxin oligomerizes into a membrane-bound, pre-pore complex prior to formation of a pore in a lipid bilayer.
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Sellman
authors.forename: B L
authors.initials: BL
authors.lastname: Kagan
authors.forename: R K
authors.initials: RK
authors.lastname: Tweten
mesh_terms: D001427:Bacterial Toxins / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C064270:hemolytic toxin, Clostridium septicum