Submitted to: US Japan Joint Conference on Cholera and Related Diarrheal Diseases
Publication Type: Abstract Only
Publication Acceptance Date: 11/15/1996
Publication Date: N/A
Technical Abstract: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the most common infectious cause of bloody diarrhea in the U.S. Hemolytic uremic syndrome, a life-threatening sequela of EHEC O157:H7 infection, is the primary cause of acute kidney failure in children in the U.S. In the U.S., most of the cases of EHEC O157:H7 disease have occurred as a consequence of ingestion of undercooked, contaminated hamburger. Both dairy and beef cattle are symtomatically and sporadically infected with this organism. Our long-term goal is to develop an inexpensive, effective vaccine to prevent cattle from becoming infected with EHEC O157:H7 and thus block transmission of the organism to humans. The candidate we have selected for the anti-transmission vaccine is intimin (also called eaeA for the product of the E. coli attaching and effacing locus A), an outer membrane protein adhesin of EHEC O157;H7, other EHEC and enteropathogenic E. coli. Our reasons for adopting intimin as a potential bovine vaccine are based on these observations. We constructed a deletion in eaeA in EHEC O157:H7 strain 86-24 and showed that intimin is required for intimate attachment of these organisms to tissue culture cells and for formation of A/E lesions in gnotobiotic pigs. Antisera to purified intimin blocked adherence to tissue culture cells. Neonatal calves fed the wild type strain 86-24 had diarrhea and A/E lesions within 48 h, but calves fed the eaeA-negative mutant had no diarrhea or A/E lesions. Levels of the mutant strain were 1-4 logs lower than the wild type throughout the G.I. tract. These findings support the hypothesis that anti-intimin antibodies will prevent or reduce colonization of calves by EHEC O157:H7.