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Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

Jihong Li, Francisco A Uzal, Bruce A McClane
Clostridium perfringens is a major cause of histotoxic and intestinal infections of humans and other animals. This Gram-positive anaerobic bacterium can produce up to three sialidases named NanH, NanI, and NanJ. The role of sialidases in histotoxic infections, such as gas gangrene (clostridial myonecrosis), remains equivocal. However, recent in vitro studies suggest that NanI may contribute to intestinal virulence by upregulating production of some toxins associated with intestinal infection, increasing the binding and activity of some of those toxins, and enhancing adherence of C...
November 19, 2016: Toxins
Francisco A Uzal, Bruce A McClane, Jackie K Cheung, James Theoret, Jorge P Garcia, Robert J Moore, Julian I Rood
The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease...
August 31, 2015: Veterinary Microbiology
Dragana Stanley, Shu-Biao Wu, Nicholas Rodgers, Robert A Swick, Robert J Moore
Clostridium perfringens causes enteric diseases in animals and humans. In poultry, avian-specific C. perfringens strains cause necrotic enteritis, an economically significant poultry disease that costs the global industry over $2 billion annually in losses and control measures. With removal of antibiotic growth promoters in some countries this disease appears to be on the rise. In experimental conditions used to study disease pathogenesis and potential control measures, reproduction of the disease relies on the use of predisposing factors such as Eimeria infection and the use of high protein diets, indicating complex mechanisms involved in the onset of necrotic enteritis...
2014: PloS One
Bhoj Kumar, Syed Imteyaz Alam, Om Kumar
Epsilon toxin (ETX) is an extremely potent pore-forming toxin and a category B biological agent. ETX is a major virulence determinant of Clostridium perfringens toxinotypes B and D, and is implicated in pathogenesis of rapidly fatal economically important pulpy kidney disease in lambs caused by toxinotype D. Despite being a toxin, ETX can be utilized as a tool to target glutamatergic neurons and for drug delivery into the CNS. 2DE-MS approach was employed to elucidate the host response to ETX following intravenous injection in mouse model...
January 2013: Proteomics
Francisco A Uzal, Bruce A McClane
Rabbits, mice, rats, non-human primates, sheep and cattle have been used to study the effect of Clostridium perfringens enterotoxin (CPE). CPE produces mostly necrosis of the small intestinal epithelium along with fluid accumulation in rabbits and mice. In the latter, CPE can bind to internal organs such as the liver, which induces lethal potassium levels in blood.
October 2012: Microbes and Infection
F Popescu, M Wyder, C Gurtner, J Frey, R A Cooke, A R Greenhill, H Posthaus
Clostridium perfringens type C causes fatal necrotizing enteritis in different mammalian hosts, most commonly in newborn piglets. Human cases are rare, but the disease, also called pigbel, was endemic in the Highlands of Papua New Guinea. Lesions in piglets and humans are very similar and characterized by segmental necro-hemorrhagic enteritis in acute cases and fibrino-necrotizing enteritis in subacute cases. Histologically, deep mucosal necrosis accompanied by vascular thrombosis and necrosis was consistently reported in naturally affected pigs and humans...
November 21, 2011: Veterinary Microbiology
Francisco A Uzal, Juliann Saputo, Sameera Sayeed, Jorge E Vidal, Derek J Fisher, Rachael Poon, Vicki Adams, Mariano E Fernandez-Miyakawa, Julian I Rood, Bruce A McClane
Clostridium perfringens type C isolates cause enterotoxemias and enteritis in humans and livestock. While the major disease signs and lesions of type C disease are usually attributed to beta toxin (CPB), these bacteria typically produce several different lethal toxins. Since understanding of disease pathogenesis and development of improved vaccines is hindered by the lack of small animal models mimicking the lethality caused by type C isolates, in this study we developed two mouse models of C. perfringens type C-induced lethality...
December 2009: Infection and Immunity
R A Moxley, G E Duhamel
Enteric bacterial infections are among the most common and economically significant diseases affecting swine production worldwide. Clinical signs of these infections include diarrhea, reduced growth rate, weight loss, and death of preweaned, weanling, grower-finisher, young and adult age breeding animals. The most common etiological agents include Escherichia coli, Clostridium perfringens, Lawsonia intracellularis, Salmonella enterica, and Brachyspira (Serpulina) spp. With the exception of Brachyspira (Serpulina) hyodysenteriae, the cause of swine dysentery, and Lawsonia intracellularis, the cause of proliferative enteropathy, the pathological changes seen with these agents closely resemble the diseases occurring in human beings...
1999: Advances in Experimental Medicine and Biology
R W Titball
A variety of pathogenic bacteria produce phospholipases C, and since the discovery in 1944 that a bacterial toxin (Clostridium perfringens alpha-toxin) possessed an enzymatic activity, there has been considerable interest in this class of proteins. Initial speculation that all phospholipases C would have lethal properties has not been substantiated. Most of the characterized enzymes fall into one of four groups of structurally related proteins: the zinc-metallophospholipases C, the sphingomyelinases, the phosphatidylinositol-hydrolyzing enzymes, and the pseudomonad phospholipases C...
June 1993: Microbiological Reviews
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