THE ROLE OF THE EAEA GENE IN DIARRHEA AND NEUROLOGICAL COMPLICATIONS IN A GNOTOBIOTIC PIGLET MODEL OF ENTEROHEMORRHAGIC ESCHERICHIA-COLI INFECTION

We reported previously that mutation of the chromosomal gene eaeA from enterohemorragic Escherichia coli (EHEC) serotype O157:H7 prevented bacterial attachment in vivo, Attachment was restored when the EHEC or enteropathogenic E. coli (EPEC) eaeA gene was introduced into the mutant on a plasmid. In this communication we have compared in gnotobiotic piglets the;pathogenicities of wild-type O157:H7 strain 86-24 and its eaeA mutant UMD619 with those of the two plasmid -complemented strains expressing Intimin(O157) (EHEC) and Intimin(0127) (EPEC). 86-24 colonized the surface and glandular epithelium of the large intestine and induced diarrhea, while UMD619 did not colonize any intestinal site and induced little or no diarrhea, Surprisingly, strain UMD619 expressing Intimin(0127) behaved in pigs more like EPEC than EHEC strains; it colonized the distal half of the small intestine and the surface of the large intestine, inducing serious diarrhea. In contrast, strain UMD619 expressing Intimin(O157) colonized the colon extremely poorly, inducing little or no diarrhea. While only the two strains causing extensive attachment-86-24 and UMD619 expressing intimin(0127)-induced diarrhea, neurological symptoms attributed to Shiga-like toxin Il occurred equally in ail four groups of animals. The intimate bacterial attachment and mucosal damage were not a prerequisite for Shiga-like toxin II translocation from the gut lumen into the circulation. Intimin(0127) appears not only to facilitate intimate attachment to cells but also to influence the site of intestinal colonization and other characteristics of EPEC infection.