Pathogenicity of Escherichia coli O157:H7 in the intestines of neonatal calves

Abstract

Cattle are an important reservoir of Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains, foodborne pathogens that cause hemorrhagic colitis and hemolytic uremic syndrome in humans. EHEC O157:H7 strains are not pathogenic in calves >3 weeks old. Our objective was to determine if EHEC O157:H7 strains are pathogenic in neonatal calves. Calves <36 h old inoculated with EHEC O157:H7 developed diarrhea and enterocolitis with attaching and effacing (A/E) lesions in both the large and small intestines by 18 h postinoculation. The severity of diarrhea and inflammation, and also the frequency and extent of A/E lesions, increased by 3 days postinoculation. We conclude that EHEC O157:H7 strains are pathogenic in neonatal calves. The neonatal calf model is relevant for studying the pathogenesis of EHEC O157:H7 infections in cattle. It should also be useful for identifying ways to reduce EHEC O157:H7 infections in cattle and thus reduce the risk of EHEC O157:H7 disease in humans. Escherichia coli strains of serotype O157:H7 belong to a family of pathogenic E. coli called enterohemorrhagic E. coli (EHEC) strains that cause hemorrhagic colitis, bloody or nonbloody diarrhea, and hemolytic uremic syndrome in humans. EHEC strains are characterized by the production of cytotoxins called Shiga toxins (Stx1 and Stx2) or verotoxins that induce microvascular changes in vivo, are paralytic and lethal for mice, and are cytotoxic for selected cell lines in vitro (19, 29, 37). EHEC O157:H7 strains colonize and produce characteristic attaching and effacing (A/E) lesions in the intestines of gnotobiotic piglets, rabbits, and chickens and produce A/E lesions in selected cell lines in vitro (22, 45). A/E lesions have not been detected in EHEC-infected mice (42) or in humans with EHEC O157:H7 infection (13, 15, 17, 20, 21, 27, 32-34). EHEC strains can be food-borne pathogens, and cattle are important reservoirs of EHEC O157:H7 strains. Food-borne outbreaks have on several occasions been attributed to the consumption of bovine products, especially contaminated and improperly cooked hamburger and raw milk (14, 19, 38, 45). The isolation of EHEC O157:H7 from the feces of healthy cattle (4, 10, 14-16, 43), from packaged bovine products (14), and from produce contaminated by bovine manure (6) supports the epidemiologic evidence of a link between human disease and consumption of bovine manure-contaminated products. One strategy for reducing the risk of EHEC O157:H7 infections in humans is to reduce the prevalence of EHEC O157:H7 infection in cattle. To accomplish this, we must first understand the pathogenesis of EHEC O157:H7 infection in cattle. The prevalence of EHEC O157:H7 in the feces of dairy calves and feedlot cattle is low. These bacteria have been isolated from 0.3 to 2.2% of fecal samples collected from healthy calves or cattle in the United States, Canada, the United Kingdom, Germany, and Spain (1, 14). Following experimental inoculation with E. coli 3081, an EHEC O157:H7 strain isolated from a healthy calf, cal...

Attaching-effacing Escherichia coli Infections in Cattle

“…Dean-Nystrom and colleagues [49][50][51] demonstrated by experimental inoculation that E coli O157:H7 can cause A/E lesions, enterocolitis and diarrhea in both colostrumdeprived and colostrum-fed neonatal calves, and A/E lesions without diarrhea in 3to 4-month-old weaned calves. In addition, they demonstrated that intimin expression by the infecting organism is necessary for the formation of A/E lesions and subsequent colonization.…”

“…In addition, they demonstrated that intimin expression by the infecting organism is necessary for the formation of A/E lesions and subsequent colonization. 50 Dean-Nystrom and colleagues 49 reported, ''EHEC O157:H7 pathogenicity in cattle appears to be age related, even within the neonatal period.'' The virulence of EHEC O157:H7 bacteria was greater in calves inoculated when less than 12 hours old than in those 30 to 36 hours old.…”

Clinical signs, reproduction of attaching/effacing lesions, and enterocyte invasion after oral inoculation of an O118 enterohaemorrhagic in neonatal calves

“…Coexistence between EPEC/EHEC strains and other diarrhoeagenic agents has already been noticed in field studies and may be related to the severity and persistance of diarrhoea in farms [5]. The age of the animal is also important: with strains of serotypes O157:H7 and O26:H11 clinical signs could not be reproduced in calves aged one to two weeks but could be reproduced well in newborn calves [1,6,7,18]. The opposite situation may exist for strains belonging to other serotypes, mimicking the situation of EPEC in rabbits [21,26].…”

“…As no other classical diarrhoeagenic infectious agents were isolated from these two calves and as the control calf did not develop diarrhoea [7], the O118:H16 EHEC strain can be considered the cause of diarrhoea. It may be argued that challenge with any bacteria would cause the appearance of diarrhoea.…”

“…The transposition in vivo of these in vitro models has been realized for the first three steps with human and rabbit EPEC by testing mutants [10,21], but the in vivo significance of the fourth step, the cellular invasion, is still unknown. Bovine EPEC and EHEC also possess a LEE [12], and AE lesions and /or clinical signs have been experimentally reproduced in young calves and lambs, with bovine EHEC belonging to various serotypes: O5:K4:Nm, O26:K-:H11, O111:Nm, and O157:H7 [1,7,18,23,29,32]. Bovine EPEC and EHEC belonging to other serotypes have, however, not been tested in vivo yet.…”