1. Mouse models for studying Clostridium perfringens type C infections

UZAL F.A; SAPUTO J.; SAYEEDS.; VIDAL J. E; FISHER D. J.; POON R; ADAMS V; FERNANDEZ MIYAKAWA ME; ROOD JI; MCCLANE BA

Roma, Italia

Congreso; Clostridia:The Impact of Genomics on Disease Control 6th ClostPath International Conference; 2009

Clostridium perfringens type C causes enterotoxaemia and necrotizing enteritis inhumans and almost all livestock species. It is believed that lethality of type Cdisease involves absorption of toxin(s) from the intestines to the circulation, but thishas never been proved. In response, we developed two mouse challenge modelsthat mimicked C. perfringens type C lethality. When inoculated by intragastricgavage, Balb/C mice showed lethality using 7 of 14 pathogenic type C isolates.Inoculated directly into the duodenum, all 14 strains produced lethality. Prior todeath, clinical signs of those challenged mice included respiratory distress,abdominal distension, neurological alterations and depression. At necropsy thesmall, and occasionally the large intestine, were dilated and gas-filled in most micedeveloping a clinical response. Histological changes in the gut were relatively mildand consisted mostly of attenuation of the mucosa with villus blunting. A type CΔcpb mutant showed no lethality in the oral model, while its lethality wasattenuated in the intraduodenal model. However, a type C Δplc or ΔpfoA mutantshowed only a slight decrease in lethality for mice. Mice could be protected againstlethality by intravenous passive immunization with a beta toxin antibody prior tooral challenge. This study provides two new mouse models for studying thepathogenic mechanism of C. perfringens type C-induced lethality and suggests thatbeta toxin is the most important toxin contributor to the systemic effects of type Cinfection.