Escherichia coliHarboring Shiga Toxin 2 Gene Variants: Frequency and Association with Clinical Symptoms

Abstract

Shiga toxin (Stx)-producing Escherichia coli (STEC) from patients with hemolytic-uremic syndrome (HUS), patients with diarrhea without HUS, or asymptomatic subjects were genotyped to assess associations between stx2 variants and clinical manifestations of infection. Neither stx2d nor stx2e was found in 268 STEC isolates from patients with HUS. Of 262 STEC isolates from patients with diarrhea, stx(2d) was found in 41 (15.6%; P<.000001), and stx2e was found in 12 (4.6%; P=.0004). The stx2c genotype frequency was similar among isolates from patients with HUS (3.7%) and diarrhea (5.0%). The frequencies of stx2c, stx2d, and stx2e among 96 STEC isolates from asymptomatic subjects were comparable to those among isolates from patients with diarrhea. None of the 626 STEC isolates contained stx2f. All stx2d-positive or stx2e-positive STEC isolates were eae negative and originated from subjects older than those with STEC isolates with stx2c. stx2c-positive STEC isolates can cause HUS, but the presence of stx2d or stx2e may predict a milder disease with a minimal risk of HUS.

Evaluation of Major Types of Shiga Toxin 2e-Producing Escherichia coli Bacteria Present in Food, Pigs, and the Environment as Potential Pathogens for Humans

“…The low incidence of Stx2e strains in human patients could indicate that most of these strains cannot colonize or may infect but do not cause disease in humans. This is supported by epidemiological findings indicating that Stx2e strains are very rarely isolated from humans, and those patients show mild diarrheal symptoms or are asymptomatic carriers (4,17,39,42). In a previous study we have found that Stx2e-producing strains differ largely in the amount of Stx2e produced (2).…”

“…The stx 2e gene is associated with E. coli serotypes that have not been described as bacterial hosts for other types of Stx so far (4,16,17,39,42). Additionally, the stx 2e gene was not reported to be present in typical and atypical EHEC strains causing bloody diarrhea and HUS, except for one case reported in 1994 (11,36,43).…”

“…In contrast, Stx2e-producing STEC bacteria are rarely isolated from humans and account for only 0.9 to 1.7% of human STEC isolates (4,42). A significant association between Stx2e and human diarrhea was not found, and it was suggested that these STEC bacteria are not important as human pathogens (4,17,19,42).…”

“…Toxins of the Stx1 and Stx2 families can be divided further into subtypes differing in the composition of their A or B subunit (40). Studies on human virulent EHEC have revealed that certain toxin types, such as Stx2, Stx2c, and activatable Stx2d, are significantly associated with higher virulence of the bacteria for humans, which may cause severe diseases such as hemorrhagic colitis and HUS (4,7,17,22,36). In pigs, the toxin type Stx2e was identified as a key factor contributing to the pathogenicity of porcine STEC and therefore was designated the edema disease principle (1).…”

Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice

“…Stx are formed by a single A subunit, which possesses N-glycosidase activity to the 28S rRNA and promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide (Gb3Cer) at the surface of host cells (9,10). Although two major types (Stx1 and Stx2) and several subtypes (variants) have been described, Stx2 and its variant Stx2c are the toxins found most frequently in severe HUS cases among EHEC-infected subjects (11,12). Stx1 and Stx2 differ significantly both in amino acid sequences and in biological functions (13,14).…”