Nature and distribution of mucosal lesions associated with enteropathogenic and enterohemorrhagic Escherichia coli in piglets and the role of plasmid-mediated factors

Abstract

Bacterial attachment-effacement (att-eff) is emerging as an important virulence characteristic common to both enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). The contribution of the plasmid-encoded EPEC adherence factor to the production of mucosal lesions and diarrhea was investigated in gnotobiotic piglets. Bacterial att-aff in the intestinal mucosa of piglets infected with plasmid-cured EPEC strain E2348/69 (O127) was indistinguishable from that in piglets infected with the parent strain, but the distribution of lesions was different; it occurred in the small intestines of 6 of 7 piglets infected with the parent strain compared with only 2 of 11 (P = 0.006) infected with the plasmid-cured strain. Plasmid-encoded factors in EPEC and EHEC strains did not appear to contribute to bacterial competition with normal gut microflora. Of 13 strains belonging to five EPEC serogroups, O55, O142, O26, O119, and O111, 3 fulfilled the criteria for EHEC (2 O26 and 1 O111). There were three distinct patterns of bacterial association with the intestinal mucosa of infected piglets. (i) EHEC strains caused bacterial att-eff associated with extensive destruction of surface and glandular epithelia in the large intestines with little or no inflammatory response. (ii) Some EPEC strains caused severe diarrhea which correlated with the extent of bacterial att-eff in the proximal small intestine, disruption of the epithelial cell membrane, and inflammation. It is suggested that, with respect to virulent strains, this degree of involvement determines the clinical outcome. Mildly pathogenic strains (O127 and O119), in which bacterial att-eff was restricted to the distal halves of the small and large intestines, caused little or no diarrhea. In such strains, nonimmune host factors (smaller, poorly feeding, and lethargic piglets) tended to play a determining role with regard to the degree of involvement of the small intestine and hence the clinical outcome. (iii) One strain (O55) caused illness and mucosal damage which could not be accounted for by the sparse bacterial att-eff observed in the gut. Instead, bacteria penetrated into and proliferated in the lamina propria, undermining the villous tips in the small intestine. Bacterial att-eff was the most important virulence factor in most of the strains examined, but plasmid-mediated factors facilitated bacterial adhesion in the small intestine, which may explain the reduced pathogenicity of the plasmid-cured variant of strain E2348/69 for human volunteers.