Clostridium perfringens Iota Toxin: A Successfully Shared Template for Common Enteric Pathogens

Abstract

Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or D. ETX belongs to the heptameric β-pore-forming toxins including Aeromonas aerolysin and Clostridium septicum alpha toxin, which are character- ized by the formation of a pore through the plasma membrane of eukaryotic cells and containing a β-barrel composed of 14 amphipathic β-strands. In contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin, which is responsible for enterotoxemia in animals, mainly in sheep. ETX induces perivascular edema in various tissues and accumulates particularly in the kidneys and in the brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier (BBB) and to stimulate the release of glutamate, which accounts for the nervous excitation symptoms observed in animal enterotoxemia. At the cellular level, ETX causes a rapid swelling followed by a cell death involving necrosis. Recently, ETX has been found to induce demye- lination and could be involved in demyelinating diseases like multiple sclerosis. The precise mode of action of ETX remains undetermined.