Pathogenic Potential to Humans of Bovine Escherichia coli O26, Scotland

Margo E. Chase-Topping

, Tracy Rosser, Lesley J. Allison, Emily Courcier, Judith Evans, Iain J. McKendrick, Michael C. Pearce, Ian Handel, Alfredo Caprioli, Helge Karch, Mary F. Hanson, Kevin G.J. Pollock, Mary E. Locking, Mark E.J. Woolhouse, Louise Matthews, J. Chris Low, and David L. Gally

Author affiliations: University of Edinburgh, Edinburgh, UK (M.E. Chase-Topping, E. Courcier, M.C. Pearce, M.E.J. Woolhouse); The Roslin Institute and Royal (Dick) School of Veterinary Studies, Edinburgh (T. Rosser, I. Handel, D.L. Gally); Scottish E. coli O157/VTEC Reference Laboratory, Edinburgh (L.J. Allison, M.F. Hanson); Scottish Agricultural College, Edinburgh (J. Evans, M.C. Pearce, J.C. Low); Biomathematics and Statistics Scotland, Edinburgh (I.J. McKendrick); Istituto Superiore di Sanità, Rome, Italy (A. Caprioli); University of Münster, Münster, Germany (H. Karch); Health Protection Scotland, Glasgow, UK (K.G.J. Pollock, M.E. Locking); University of Glasgow Veterinary School, Glasgow (L. Matthews)

Abstract

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin–producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx₂ in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26–associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx₂ phage acquisition.

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are gastrointestinal pathogens associated with asymptomatic carriage and human diseases ranging from mild diarrhea to hemorrhagic colitis and hemolytic uremic syndrome (HUS) (1). Worldwide, EHEC serogroup O157 strains are responsible for most human Shiga toxin–producing E. coli (STEC) infections (2). However, recent outbreaks in Germany (3) and the United States (4) have highlighted the increasing role of other Shiga toxin–producing serogroups (termed non-O157 strains) in causing human disease.

The pathogenesis of EHEC strains is associated with production of Shiga toxins expressed from lysogenic bacteriophages in the EHEC genome. There are 2 predominant classes of Shiga toxins (1 and 2), each encoded from 2 genes, stxAB, with the genotypes simplified to stx₁ or stx₂ in this study. Whereas EHEC is regarded as an emerging zoonotic pathogen, the related EPEC strains cause diarrhea, especially in infants in developing countries (1).

EPEC and EHEC express a type III secretion (T3S) system that translocates multiple effector proteins into host cells and manipulate host innate responses, which are needed for colonization (5–7). The T3S system is central to the formation of attaching and effacing lesions on the intestinal epithelium that requires the bacterial outer membrane protein intimin (encoded by eae) and the secreted bacterial protein—the translocated intimin receptor (Tir)—that is injected into the host cell. Studies of EPEC and EHEC O157 show that these pathogens trigger different actin polymerization pathways respectively involving Tir cytoskeleton coupling proteins (tccP or tccP2) (5). The formation of attaching and effacing lesions is needed for bacterial colonization by EHEC O157 and EHEC O26 in cattle. However, Shiga toxin (Stx) is the principal factor responsible for severe human illness, including HUS (8). Strains with stx₂ alone appear more strongly associated with HUS than do strains with only stx₁ (8–10). These observations have been supported by mouse (11) and primate models (12).

Among non-O157 EHEC, Stx-producing E. coli O26 also causes human disease (13–15) and has been isolated from livestock (16). However, unlike EHEC serogroup O157, it may be pathogenic for both cattle and humans (17). Although the origin of human E. coli O26 infections is rarely identified (18), evidence exists of person-to-person spread (19) and foodborne transmission (20). Furthermore, because EHEC O26 has been isolated from the feces of cattle and other animals (16,21,22), potential exists for direct and indirect zoonotic transmission to humans (20).

In the United Kingdom, Stx-producing human E. coli O26 infections are usually uncommon and not clinically severe. Most identified EHEC infections are associated with serogroup O157, and incidence rates in Scotland are among the highest, compared with rates in countries with comparable surveillance (23). In contrast with human infection rates, farm and animal prevalence of E. coli serogroups O26 and O157 are similar in Scotland (21).

Our first objective was to identify the cause of the disparity between the incidence of E. coli O157 and O26 infections among humans in Scotland by examining the natural heterogeneity among serogroup O26 strains and reexamining their prevalence in cattle. As a second objective, we used different molecular techniques to compare the relationships between E. coli O26 isolates recovered from humans and cattle.