title: The pathogenesis of necrotic enteritis in chickens: what we know and what we need to know: a review.
abstract: This review summarizes advances in understanding the pathogenesis of necrotic enteritis of chickens caused by netB-positive Clostridium perfringens. The discovery of NetB as the essential toxin trigger for the disease was followed by recognition that it forms part of a large plasmid-encoded 42 kb pathogenicity locus (NELoc-1). While the locus is critical for toxin production, it likely has additional functions related to colonization and degradation of the mucus barrier, which are essential both to multiplication and to bringing NetB close to the intestinal epithelium. Two "chitinases" (glycoside hydrolases (GHs)) present on NELoc-1 are predicted to be involved in mucin degradation, as is the large carbohydrate-binding metalloprotease, shown to be involved in mucinase activity in other clostridia. A second pathogenicity locus found in netB-positive C. perfringens, NELoc-2, also encodes a GH likely involved in mucin degradation. Upon reaching a sufficient cell density on the intestinal mucosa, the Agr-like quorum-sensing system is triggered, which in turn up-regulates the VirR/VirS regulon. This regulon includes NetB. Where NetB initiates damage is unresolved, but it may be deep in the intestinal mucosa, rather than superficially. As the disease progresses, C. perfringens line what remains of the intestinal epithelium in large numbers. This likely involves a number of different bacterial adhesins, including additional NELoc-1-encoded bacterial surface proteins, some of which may adhere to epithelial cell ligands exposed by bacterial sialidases. Further studies of the pathogenesis of necrotic enteritis should lead to development of novel ways to control the infection.
authors.affiliation: a Department of Pathobiology , University of Guelph , Guelph , Ontario , Canada.
authors.forename: John F
authors.initials: JF
authors.lastname: Prescott
authors.affiliation: a Department of Pathobiology , University of Guelph , Guelph , Ontario , Canada.
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Parreira
authors.affiliation: a Department of Pathobiology , University of Guelph , Guelph , Ontario , Canada.
authors.forename: Iman
authors.initials: I
authors.lastname: Mehdizadeh Gohari
authors.affiliation: b Agriculture and Agri-Food Canada , Guelph , Ontario , Canada.
authors.forename: Dion
authors.initials: D
authors.lastname: Lepp
authors.affiliation: b Agriculture and Agri-Food Canada , Guelph , Ontario , Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Gong
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002645:Chickens / Q000382:microbiology*; D003015:Clostridium Infections / Q000382:microbiology / Q000662:veterinary*; D003016:Clostridium perfringens / Q000235:genetics / Q000472:pathogenicity*; D004751:Enteritis / Q000382:microbiology / Q000662:veterinary*; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis / Q000662:veterinary; D010957:Plasmids / Q000235:genetics; D011201:Poultry Diseases / Q000382:microbiology*; D012307:Risk Factors; D014774:Virulence; D037521:Virulence Factors
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; C534774:NetB protein, Clostridium perfringens; D037521:Virulence Factors
keywords: Necrotic enteritis; avian; pathogenesis; review