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

Abstract

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 stx2a gene is most often present in locus of enterocyte effacement (eae)–positive STEC strains and has consistently been associated with HUS. The stx2a 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.

Genetic diversity of the intimin gene (eae) in non-O157 Shiga toxin-producing Escherichia coli strains in China

“…Strains that carry Stx2a (with or without Stx2c) are often associated with severe symptoms such as HC and HUS 35,36 . The stx 2a gene is most often present in eae positive STEC strains and has consistently been associated with HUS 37 . In this study, 6 out of 62 isolates carried stx 2a subtypes, which were isolated from diarrheal patients, yak and other unknown sources.…”

A Putative Microcin Amplifies Shiga Toxin 2a Production of Escherichia coli O157:H7

“…divided into three subtypes, Stx1a, Stx1c, and Stx1d (7). Stx2 also has multiple subtypes, designated Stx2a, Stx2b, Stx2c, Stx2d, Stx2e, Stx2f, Stx2g (7), Stx2h (8), and Stx2i (9). In general, infections caused by Stx1 and, interestingly, even those caused by both Stx1 and Stx2 (such as strains EDL933 [10] and Sakai [11]) are associated with less severe disease symptoms than Stx2-only-producing E. coli (12)(13)(14).…”

Prevalence and Epidemiology of Non-O157 Escherichia coli Serogroups O26, O103, O111, and O145 and Shiga Toxin Gene Carriage in Scottish Cattle, 2014–2015

“…Overall, the distribution of stx subtypes in the O26 STEC shedding herds was very similar to that observed in clinical strains across the same time period ( 60 ). Isolates from 5 out of the 15 O26 STEC shedding herds met the criteria for JEMRA level 1 ( 13 ), while the remainder of the stx -positive herds yielded strains equivalent to JEMRA level 4. All the identified O26 STEC herds therefore shed bacteria of substantial public health risk.…”

“…Non-O157 STEC strains are now frequently identified as the primary pathogen in both sporadic and clinical outbreaks of severe disease, including HUS and death ( 4 , 12 ). Consequently, a new classification system has recently been proposed, the JEMRA scheme ( 13 ), based upon virulence gene composition. Under this scheme, STEC strains carrying the stx 2a gene (with or without stx 1a ) together with eae are classified as JEMRA level 1, the most pathogenic tier, capable of inducing bloody diarrhea and HUS.…”