Clostridium perfringens epsilon toxin: The third most potent bacterial toxin known

• This manuscript contains a complete review about Clostridium perfringens epsilon toxin (ETX).
• Genetics, structure, activation, receptors, absorption and action of ETX are covered.
• ETX causes enterotoxemia, a highly lethal disease of domestic ruminants, mainly sheep.
• ETX is the third most potent bacterial toxin after the botulinum and tetanus toxins.
• Due to its high potency, ETX is considered a potential agent of bioterrorism.

Epsilon toxin (ETX) is produced by Clostridium perfringens type B and D strains and causes enterotoxemia, a highly lethal disease with major impacts on the farming of domestic ruminants, particularly sheep. ETX belongs to the aerolysin-like pore-forming toxin family. Although ETX has striking similarities to other toxins in this family, ETX is often more potent, with an LD50 of 100 ng/kg in mice. Due to this high potency, ETX is considered as a potential bioterrorism agent and has been classified as a category B biological agent by the Centers for Disease Control and Prevention (CDC) of the United States. The protoxin is converted to an active toxin through proteolytic cleavage performed by specific proteases. ETX is absorbed and acts locally in the intestines then subsequently binds to and causes lesions in other organs, including the kidneys, lungs and brain. The importance of this toxin for veterinary medicine and its possible use as a biological weapon have drawn the attention of researchers and have led to a large number of studies investigating ETX. The aim of the present work is to review the existing knowledge on ETX from C. perfringens type B and D.