title: Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications.
abstract: Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. jcf63@pitt.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Freedman
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. ars139@pitt.edu.
authors.forename: Archana
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. bamcc@pitt.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
mesh_terms: D000818:Animals; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D005767:Gastrointestinal Diseases / Q000378:metabolism; D006801:Humans; D014612:Vaccines
chemical_list: D004768:Enterotoxins; D014612:Vaccines; C035598:enterotoxin, Clostridium
keywords: Clostridium perfringens; claudins; enterotoxin; pore-forming toxin; sporulation; tight junctions