Escherichia coli O157:H7 causes bloody diarrhea and potentially fatal systemic sequelae in humans. Cattle are most frequently identified as the primary source of infection, and E. coli O157:H7 generally colonizes the gastrointestinal tracts of cattle without causing disease. In this study, persistence and tropism were assessed for four different E. coli O157:H7 strains. Experimentally infected calves shed the organism for at least 14 days prior to necropsy. For the majority of these animals, as well as for a naturally colonized animal obtained from a commercial beef farm, the highest numbers of E. coli O157:H7 were found in the feces, with negative or significantly lower levels detected in lumen contents taken from the gastrointestinal tract. Detailed examination demonstrated that in these individuals the majority of tissue-associated bacteria were adherent to mucosal epithelium within a defined region extending up to 5 cm proximally from the recto-anal junction. The tissue targeted by E. coli O157:H7 was characterized by a high density of lymphoid follicles. Microcolonies of the bacterium were readily detected on the epithelium of this region by immunofluorescence microscopy. As a consequence of this specific distribution, E. coli O157:H7 was present predominately on the surface of the fecal stool. In contrast, other E. coli serotypes were present at consistent levels throughout the large intestine and were equally distributed in the stool. This is a novel tropism that may enhance dissemination both between animals and from animals to humans. The accessibility of this site may facilitate simple intervention strategies.Enterohemorrhagic Escherichia coli (EHEC) has emerged as an important cause of human intestinal disease in developed countries over the past 20 years. In addition to bloody diarrhea, intestinal infection can lead to potentially fatal systemic sequelae resulting from the activity of Shiga toxins. The majority of these infections are caused by E. coli O157:H7 (21,26). This serotype has been frequently isolated from cattle feces, and most human EHEC O157:H7 infections originate, either directly or indirectly, from this source (5, 8). A key step in protecting public health is to know how and where the bacterium persists in this major animal reservoir. Until now, no defined site of colonization by E. coli O157:H7 in the bovine gastrointestinal tract (GIT) has been described, beyond an affinity for the large intestine (17).Enteropathogenic E. coli (EPEC) and most EHEC strains are known to carry a locus of enterocyte effacement (LEE) pathogenicity island (24). This locus encodes a type III secretion system that mediates attachment to mucosal epithelial cells. Injection of effector proteins results in intimate attachment and characteristic attaching and effacing (A/E) lesions dependent on intimin and Tir (translocated intimin receptor) (16,22). E. coli O157:H7 intimately attaches to a variety of cell types and tissues in vitro, and a few studies have demonstrated that E. coli O157:H7 can form A/E lesions ...

Identification of the relative importance of within-and betweenhost variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: Ϸ80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within-and betweenhost variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R 0, could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R 0 by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.bacterial count ͉ core groups ͉ super shedder ͉ superspreading ͉ targeted control T he role of heterogeneous infectiousness on the course of disease outbreaks was highlighted during the recent severe acute respiratory syndrome outbreak (1), in which a few individuals were responsible for a disproportionate number of transmission events. Awareness of heterogeneities in transmission dynamics can be important for the effective implementation of disease control measures and can lead to efficient targeting of interventions at a subset of the population (2-5). Factors that might lead to such heterogeneities include variability in infectiousness, exposure, genetic susceptibility, contact rates, and behavior (6-10). Quantifying their impact on the transmission dynamics can be achieved through direct methods, such as contact tracing and outbreak reconstruction (1, 11), or indirectly through their effect on the distribution of infected cases (12).Escherichia coli O157 is an important zoonosis with a known reservoir in cattle (13,14). Prevalences of infection are generally low, usually reported to be Ͻ10% of animals carrying the pathogen (14). Typically, however, the distribution of prevalences is highly skewed (15); at any one time, shedding is not detected in the majority of cattle groups, but a small proportion of groups contains high numbers of individuals shedding bacteria in their feces.The range of prevalences of an infectious agent in a small population is expected to be influenced both by stochasticity and underlying heterogeneities in the transmission dynamics. In a recent a...

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Shiga-toxin-producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the emergence of this serotype in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains observed today. In this study, the genomes of over 1000 isolates from both human clinical cases and cattle, spanning the history of STEC O157:H7 in the UK, were sequenced. Phylogenetic analysis revealed the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimated the time to evolution of the most recent common ancestor of the current circulating global clone to be 175 years ago. This event was followed by rapid diversification. We show the acquisition of specific virulence determinates has occurred relatively recently and coincides with its recent detection in the human population. We used clinical outcome data from 493 cases of STEC O157:H7 to assess the relative risk of severe disease including haemolytic uraemic syndrome from each of the defined clades in the population and show the dramatic effect Shiga toxin repertoire has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years, one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. There is a need to understand the selection pressures maintaining Shiga-toxin-encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations.

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