Enteropathogenic Escherichia coli enteritis: evaluation of the gnotobiotic piglet as a model of human infection.

Abstract
The pathogenicity of classical enteropathogenic Escherichia coli strains of human origin was investigated in gnotobiotic piglets. One to two day old piglets in groups of four were infected perorally with approximately 10(8) colony forming units of one of eight enteropathogenic E coli strains or a non-pathogenic control strain. Animals were necropsied 24 or 48 hours after infection and their intestines were subjected to histological examination, quantitative bacterial culture and estimation of lactase activity. Four enteropathogenic E coli strains caused mild to moderate diarrhoea in nine of the 16 piglets inoculated with them. Piglets given two of these strains later became moribund. One enteropathogenic E coli strain caused a severe illness unaccompanied by diarrhoea. Inflammation of the intestinal mucosa occurred with all eight enteropathogenic E coli strains, but not with the control strain. Pathological changes were most pronounced in the distal ileum and colon and adherent bacteria were seen on the surface of the inflamed mucosa. The extent of the inflammatory response in infected piglets for the most part paralleled the severity of the clinical signs, the degree of bacterial colonisation and the reduction in lactase activity. Electron microscopic examination of tissue from piglets infected with three different strains showed that bacterial adherence to the apical plasma membrane of epithelial cells was accompanied by distinctive ultrastructural changes. These included degeneration of the microvillous brush border, together with cupping and pedestal formation of the plasma membrane at sites of bacterial attachment. The same changes have been seen in naturally occurring enteropathogenic E coli diarrhoea in humans and rabbits. The combined clinical and pathological findings indicate that the neonatal gnotobiotic piglet is a suitable model of infection with enteropathogenic E coli.