title: Perfringolysin O: The Underrated Clostridium perfringens Toxin?
abstract: The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin), a pore-forming cholesterol-dependent cytolysin (CDC). PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol. Membrane-bound monomers undergo structural changes that culminate in the formation of an oligomerized prepore complex on the membrane surface. The prepore then undergoes conversion into the bilayer-spanning pore measuring approximately 250-300 Å in diameter. PFO is expressed in nearly all identified C. perfringens strains and harbors interesting traits that suggest a potential undefined role for PFO in disease development. Research has demonstrated a role for PFO in gas gangrene progression and bovine necrohemorrhagic enteritis, but there is limited data available to determine if PFO also functions in additional disease presentations caused by C. perfringens. This review summarizes the known structural and functional characteristics of PFO, while highlighting recent insights into the potential contributions of PFO to disease pathogenesis.
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. s.verherstraeten@gmail.com.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Verherstraeten
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. evy.goossens@ugent.be.
authors.forename: Evy
authors.initials: E
authors.lastname: Goossens
authors.affiliation: Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. bonnie.valgaeren@ugent.be.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Valgaeren
authors.affiliation: Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. bart.pardon@ugent.be.
authors.forename: Bart
authors.initials: B
authors.lastname: Pardon
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. leen.timbermont@ugent.be.
authors.forename: Leen
authors.initials: L
authors.lastname: Timbermont
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. freddy.haesebrouck@ugent.be.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. richard.ducatelle@ugent.be.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. piet.deprez@ugent.be.
authors.forename: Piet
authors.initials: P
authors.lastname: Deprez
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. kristin-wade@ouhsc.edu.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Wade
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. rodney-tweten@ouhsc.edu.
authors.forename: Rodney
authors.initials: R
authors.lastname: Tweten
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. filip.vanimmerseel@ugent.be.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Immerseel
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D002462:Cell Membrane / Q000378:metabolism; D003016:Clostridium perfringens / Q000235:genetics / Q000378:metabolism; D006460:Hemolysin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D006801:Humans
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin
keywords: calves; cholesterol-dependent cytolysin; enterotoxaemia; gas gangrene; myonecrosis; necrohemorrhagic enteritis