Development of a porcine model for investigation of Campylobacter jejuni diarrhoeal disease

Campylobacter jejuni causes acute diarrhoea in humans, acquired from food, particularly poultry, other meat products, untreated water and unpasteurized milk. How this organism causes the symptoms of diarrhoea in man is currently not well understood. The purpose of this project is to develop a disease model in piglets who also get acute diarrhoeal disease when they acquire this organism. Two different models of piglet diarrhoea will be used - the gnotobiotic or germ free piglet and a colostrum deprived model. These pigs get watery or inflammatory diarrhoea respectively, similar to the clinical conditions described in human disease. We will use these disease models to determine if we can devise a strategy for screening pools of tagged mutants. This will enable us to better understand how these organisms cause diarrhoeal disease in both man and pigs.

Campylobacter jejuni causes acute diarrhoea in man which may manifest clinically as inflammatory or watery diarrhoea. The pathogenesis of these events is still poorly understood. The piglet model is similar, in terms of gut physiology, to man and has been used previously as a model of diarrhoeal disease for this organism. This proposal aims to use two piglet challenge models in order to further understand the pathogenesis of Campylobacter jejuni mediated inflammatory and watery diarrhoea. The gnotobiotic piglet model predominantly causes acute watery diarrhoea in challenged piglets, with little inflammation induced in challenged animals by gross inspection or microscopic histopathology. In contrast, colostrum deprived piglets challenged with C. jejuni have been shown to induce acute inflammatory diarrhoea. The use of these complementary models allows the testing of antibiotic tagged wild type strains (WITS) and limited pools of defined tagged Campylobacter jejuni mutants. This should help in determining if we can use a pooled tagged mutagenesis approach for identifying bacterial molecules important in this model and ultimately how this organism causes these clinical symptoms in man. In addition these challenge models allow re-investigation of the role of C. jejuni in diarrhoeal disease of the piglet.