Clostridium perfringens beta-toxin forms multimeric transmembrane pores in human endothelial cells.
Beta-toxin is one of the lethal toxins of Clostridium perfringens. It shares sequence homology with the pore-forming alpha-toxin of Staphylococcus aureus and structural homology has been indicated by mutagenesis studies. Human endothelial cells are sensitive to the toxic effect of alpha-toxin and in order to investigate the function of beta-toxin we have looked at the effect of the protein on human umbilical vein endothelial cells. We show that like alpha-toxin beta-toxin induces release of arachidonic acid in a dose dependent manner. In addition we show that both toxins cause leakage of inositol from the cells, consistent with the formation of transmembrane pores. The effect of toxin mutants on endothelial cells correlates with the lethal dose of each mutant in mice. Furthermore, we demonstrate the formation of heat stable toxin multimers in the cell membrane. Multimer formation was not observed on other cell types tested. We conclude that beta-toxin is a cell specific pore-forming toxin, structurally and functionally related to alpha-toxin of Staphylococcus aureus.
Steinthorsdottir
V
V
Institute for Experimental Pathology, University of Iceland, Reykjavik, Keldur, 112, Iceland. vstein@decode.is
Halldórsson
H
H
Andrésson
O S
OS
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003016:Clostridium perfringens / Q000472:pathogenicity*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D010738:Type C Phospholipases / Q000633:toxicity
D001427:Bacterial Toxins; C031884:CPB protein, Clostridium perfringens; D002135:Calcium-Binding Proteins; D007295:Inositol Phosphates; D016718:Arachidonic Acid; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens; D002118:Calcium