Role of Phospholipid Metabolism and G Protein in the Action Induced by Clostridium Perfringens Alpha-Toxin

Clostridium perfringens produces alpha-toxin, which is an important virulence factor in gas gangrene [1-3]. Alpha-toxin is hemolytic, dermonecrotic, and lethal. Furthermore, it has phospholipase C (PLC) and sphingomyelinase (SMase) activities [13]. The toxin has been shown to damage the membranes of various mammalian cells [1-3] as well as artificial membranes [4]. The structure of alpha-toxin shows two domains, the N-domain (residues 1-250) contains the catalytic active site and the C-domain (residues 251-370) responsible for the binding to membranes (Figure 1) [5]. The gene encoding alpha-toxin [6], Bacillus cereus PLC (BCPLC) [7], and PLCs from C. bifermentans [8] and Listeria monocytogenes [9] have been isolated and their nucleotide sequences were determined. The results show that the deduced amino acid sequences of alpha-toxin and these enzymes exhibit significant homology up to approximately 250 residues from the N-terminus. From these findings, alpha-toxin was found to belong to the PLC family. The C-domain is similar to the C2 domain of intracellular eukaryotic proteins involved in vesicular transport and signal transduction [10,11].