Mechanisms of Action and Cell Death Associated with Clostridium perfringens Toxins
California Animal Health and Food Safety Laboratory, San Bernardino Branch, School of Veterinary Medicine, University of California-Davis, San Bernardino, CA 92408, USA
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Room 420, Bridgeside Point II Building, 450 Technology Drive, Pittsburgh, PA 15219, USA
Author to whom correspondence should be addressed.
Toxins 2018, 10(5), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins10050212
Received: 27 April 2018 / Revised: 18 May 2018 / Accepted: 19 May 2018 / Published: 22 May 2018
(This article belongs to the Collection Clostridium difficile/Clostridium sordellii and Clostridium perfringens Toxins)
Clostridium perfringens uses its large arsenal of protein toxins to produce histotoxic, neurologic and intestinal infections in humans and animals. The major toxins involved in diseases are alpha (CPA), beta (CPB), epsilon (ETX), iota (ITX), enterotoxin (CPE), and necrotic B-like (NetB) toxins. CPA is the main virulence factor involved in gas gangrene in humans, whereas its role in animal diseases is limited and controversial. CPB is responsible for necrotizing enteritis and enterotoxemia, mostly in neonatal individuals of many animal species, including humans. ETX is the main toxin involved in enterotoxemia of sheep and goats. ITX has been implicated in cases of enteritis in rabbits and other animal species; however, its specific role in causing disease has not been proved. CPE is responsible for human food-poisoning and non-foodborne C. perfringens-mediated diarrhea. NetB is the cause of necrotic enteritis in chickens. In most cases, host–toxin interaction starts on the plasma membrane of target cells via specific receptors, resulting in the activation of intracellular pathways with a variety of effects, commonly including cell death. In general, the molecular mechanisms of cell death associated with C. perfringens toxins involve features of apoptosis, necrosis and/or necroptosis.