title: Molecular basis of toxicity of Clostridium perfringens epsilon toxin.
abstract: Clostridium perfringens ε-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive 32.9 kDa prototoxin is converted to active mature toxin by proteolytic cleavage, either by digestive proteases of the host, such as trypsin and chymotrypsin, or by C. perfringens λ-protease. In vivo, the toxin appears to target the brain and kidneys, but relatively few cell lines are susceptible to the toxin, and most work has been carried out using Madin-Darby canine kidney (MDCK) cells. The binding of ε-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable, high molecular weight complex. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells.
authors.affiliation: Biosciences, College of Life and Environmental Sciences, University of Exeter, UK.
authors.forename: Monika
authors.initials: M
authors.lastname: Bokori-Brown
authors.forename: Christos G
authors.initials: CG
authors.lastname: Savva
authors.forename: Sérgio P
authors.initials: SP
authors.lastname: Fernandes da Costa
authors.forename: Claire E
authors.initials: CE
authors.lastname: Naylor
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Basak
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D003016:Clostridium perfringens / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin