Abstract
BackgroundShiga toxin (Stx) are cardinal virulence factors of enterohemorrhagic E. coli O157:H7 (EHEC O157). The gene content and genomic insertion sites of Stx-associated bacteriophages differentiate clinical genotypes of EHEC O157 (CG, typical of clinical isolates) from bovine-biased genotypes (BBG, rarely identified among clinical isolates). This project was designed to identify bacteriophage-mediated differences that may affect the virulence of CG and BBG.MethodsStx-associated bacteriophage differences were identified by whole genome optical scans and characterized among >400 EHEC O157 clinical and cattle isolates by PCR.ResultsOptical restriction maps of BBG strains consistently differed from those of CG strains only in the chromosomal insertion sites of Stx2-associated bacteriophages. Multiplex PCRs (stx1, stx2a, and stx2c as well as Stx-associated bacteriophage - chromosomal insertion site junctions) revealed four CG and three BBG that accounted for >90% of isolates. All BBG contained stx2c and Stx2c-associated bacteriophage – sbcB junctions. All CG contained stx2a and Stx2a-associated bacteriophage junctions in wrbA or argW.ConclusionsPresence or absence of stx2a (or another product encoded by the Stx2a-associated bacteriophage) is a parsimonious explanation for differential virulence of BBG and CG, as reflected in the distributions of these genotypes in humans and in the cattle reservoir.
Highlights
Enterohemorrhagic E. coli O157:H7 (EHEC O157) is an important cause of food- and water-borne illnesses in developed nations
Both Bovine-biased genotypes (BBG) and clinical genotypes (CG) usually carry both EHEC O157 cardinal virulence factors: production of one or more Shiga toxin (Stx) and expression of the Locus of Enterocyte Effacement (LEE) pathogenicity island required for intestinal colonization [1,17]
This possibility was supported by the recent demonstration that CG strains cause more severe clinical signs, more severe histopathologic lesions, and higher mortality than BBG strains in two animal models of human disease [15]
Summary
Enterohemorrhagic E. coli O157:H7 (EHEC O157) is an important cause of food- and water-borne illnesses in developed nations. Other genotyping methods demonstrate a similar bias in distribution of EHEC O157 lineages/clades among cattle and human host [6,8,12] Both BBG and CG usually carry both EHEC O157 cardinal virulence factors: production of one or more Stx and expression of the Locus of Enterocyte Effacement (LEE) pathogenicity island required for intestinal colonization [1,17]. The gene content and genomic insertion sites of Stx-associated bacteriophages differentiate clinical genotypes of EHEC O157 (CG, typical of clinical isolates) from bovine-biased genotypes (BBG, rarely identified among clinical isolates).
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