PMID:18078439

Citation	Sayeed, S, Uzal, FA, Fisher, DJ, Saputo, J, Vidal, JE, Chen, Y, Gupta, P, Rood, JI and McClane, BA (2008) Beta toxin is essential for the intestinal virulence of Clostridium perfringens type C disease isolate CN3685 in a rabbit ileal loop model. Mol. Microbiol. 67:15-30
Abstract	Clostridium perfringens type C isolates, which cause enteritis necroticans in humans and enteritis and enterotoxaemias of domestic animals, typically produce (at minimum) beta toxin (CPB), alpha toxin (CPA) and perfringolysin O (PFO) during log-phase growth. To assist development of improved vaccines and therapeutics, we evaluated the contribution of these three toxins to the intestinal virulence of type C disease isolate CN3685. Similar to natural type C infection, log-phase vegetative cultures of wild-type CN3685 caused haemorrhagic necrotizing enteritis in rabbit ileal loops. When isogenic toxin null mutants were prepared using TargeTron technology, even a double cpa/pfoA null mutant of CN3685 remained virulent in ileal loops. However, two independent cpb null mutants were completely attenuated for virulence in this animal model. Complementation of a cpb mutant restored its CPB production and intestinal virulence. Additionally, pre-incubation of wild-type CN3685 with a CPB-neutralizing monoclonal antibody rendered the strain avirulent for causing intestinal pathology. Finally, highly purified CPB reproduced the intestinal damage of wild-type CN3685 and that damage was prevented by pre-incubating purified CPB with a CPB monoclonal antibody. These results indicate that CPB is both required and sufficient for CN3685-induced enteric pathology, supporting a key role for this toxin in type C intestinal pathogenesis.
Links	PubMed Online version:10.1111/j.1365-2958.2007.06007.x
Keywords	Animals; Antibodies, Bacterial/immunology; Antibodies, Monoclonal/immunology; Antitoxins/immunology; Bacterial Toxins/genetics; Bacterial Toxins/immunology; Bacterial Toxins/metabolism; Bacterial Toxins/toxicity; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Clostridium Infections/microbiology; Clostridium Infections/veterinary; Clostridium perfringens/classification; Clostridium perfringens/immunology; Clostridium perfringens/pathogenicity; Disease Models, Animal; Female; Genotype; Hemolysin Proteins/genetics; Hemolysin Proteins/metabolism; Humans; Ileal Diseases/microbiology; Ileal Diseases/pathology; Ileal Diseases/veterinary; Ileum/microbiology; Ileum/pathology; Male; Mutagenesis, Insertional; Phenotype; Rabbits; Sheep Diseases/microbiology; Type C Phospholipases/genetics; Type C Phospholipases/metabolism; Virulence Factors/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CLOPE:TACY		GO:0044179: hemolysis in other organism	ECO:0000315:		P		Figure 3.A shows that the pfo wild type strain grew hemolytic colonies and the pfo mutant strain grew non hemolytic colonies on sheep blood agar.	complete CACAO 4594
CLOPE:TACY	involved_in	GO:0044179: hemolysis in other organism	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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