Hazard Identification and Characterization: Criteria for Categorizing Shiga Toxin-Producing Escherichia coli on a Risk Basis

Shiga toxin-producing Escherichia coli (STEC) comprise a large, highly diverse group of strains. Since the emergence of STEC serotype O157:H7 as an important foodborne pathogen, serotype data have been used for identifying STEC strains, and this use continued as other serotypes were implicated in human infections. An estimated 470 STEC serotypes have been identified, which can produce one or more of the 12 known Shiga toxin (Stx) subtypes. The number of STEC serotypes that cause human illness varies but is probably higher than 100. However, many STEC virulence genes are mobile and can be lost or transferred to other bacteria; therefore, STEC strains that have the same serotype may not carry the same virulence genes or pose the same risk. Although serotype information is useful in outbreak investigations and surveillance studies, it is not a reliable means of assessing the human health risk posed by a particular STEC serotype. To contribute to the development of a set of criteria that would more reliably support hazard identification, this review considered each of the factors contributing to a negative human health outcome: mild diarrhea, bloody diarrhea, and hemolytic uremic syndrome (HUS). STEC pathogenesis involves entry into the human gut (often via ingestion), attachment to the intestinal epithelial cells, and elaboration of Stx. Production of Stx, which disrupts normal cellular functions and causes cell damage, alone without adherence of bacterial cells to gut epithelial cells is insufficient to cause severe illness. The principal adherence factor in STEC is the intimin protein coded by the eae gene. The aggregative adherence fimbriae adhesins regulated by the aggR gene of enteroaggregative E. coli strains are also effective adherence factors. The stx(2a) gene is most often present in locus of enterocyte effacement (eae)-positive STEC strains and has consistently been associated with HUS. The stx(2a) gene has also been found in eae-negative, aggR-positive STEC that have caused HUS. HUS cases where other stx gene subtypes were identified indicate that other factors such as host susceptibility and the genetic cocktail of virulence genes in individual isolates may affect their association with severe diseases.