Shiga Toxin–Producing<i>Escherichia coli</i>Serotype OX3:H21 as a Cause of Hemolytic‐Uremic Syndrome

Keskimäki, Markku; Ikäheimo, Risto; Kärkkäinen, Päivi; Scheutz, Flemming; Ratiner, Yuli A.; Puohiniemi, Ritvaleena; Siitonen, Anja

doi:10.1086/513668

Cited by 32 publications

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“…Isolates of serotypes O1:H20, O2:H29, O174: H8, and O174:H21, which have been identified to carry stx 2d , have previously been isolated from healthy or symptomatic humans in a variety of countries (14,15,27,33).…”

Section: Discussionmentioning

confidence: 99%

Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

2003

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Stx2d is a recently described Shiga toxin whose cytotoxicity is activated 10-to 1,000-fold by the elastase present in mouse or human intestinal mucus. We examined Shiga toxigenic Escherichia coli (STEC) strains isolated from food and livestock sources for the presence of activatable stx 2d . The stx 2 operons of STEC were first analyzed by PCR-restriction fragment length polymorphism (RFLP) analysis and categorized as stx 2 , stx 2c vha , stx 2c vhb , or stx 2d EH250 . Subsequently, the stx 2c vha and stx 2c vhb operons were screened for the absence of a PstI site in the stx 2A subunit gene, a restriction site polymorphism which is a predictive indicator for the stx 2d (activatable) genotype. Twelve STEC isolates carrying putative stx 2d operons were identified, and nucleotide sequencing was used to confirm the identification of these operons as stx 2d . The complete nucleotide sequences of seven representative stx 2d operons were determined. Shiga toxin expression in stx 2d isolates was confirmed by immunoblotting. stx 2d isolates were induced for the production of bacteriophages carrying stx. Two isolates were able to produce bacteriophages 1662a and 1720a carrying the stx 2d operons. RFLP analysis of bacteriophage genomic DNA revealed that 1662a and 1720a were highly related to each other; however, the DNA sequences of these two stx 2d operons were distinct. The STEC strains carrying these operons were isolated from retail ground beef. Surveillance for STEC strains expressing activatable Stx2d Shiga toxin among clinical cases may indicate the significance of this toxin subtype to human health.Shiga toxigenic Escherichia coli (STEC) isolates are important food-borne pathogens that exist as commensal bacteria of ruminant animals. Shiga toxins (Stxs) comprise an A subunit that carries the toxic function and a B-subunit pentamer that binds the toxin to the eukaryotic cell receptor (for a review, see reference 22). Studies have indicated that Stx type 2 (Stx2), encoded by the stx 2 operon, has an epidemiological relationship with the severe human disease conditions hemolytic-uremic syndrome and hemorrhagic colitis. In addition, toxins Stx2 and Stx2c, encoded by different genotypic subtypes of stx 2 , have also been associated with a greater severity of human disease. In contrast, the more recently described stx 2 genotype, stx 2d EH250 (26), is apparently of lesser clinical significance.The nomenclature designating the Stx2d EH250 subtype is complicated by the prior use of Stx2d to designate activatable Stx2 (16,18). Both Stx2d and Stx2d EH250 possess Ser291 and Glu297 residues in the Stx2A subunit toxin-coding region; however, only Stx2d is activatable. While STEC isolates carrying stx 2d EH250 are commonly found, particularly from sheep (8), very few reports describe activatable stx 2d genotype in STEC.Activatable stx 2d was originally detected in STEC strain B2F1. Two activatable operons, stx 2d1 and stx 2d2 , have been identified in the B2F1 (17). Prior to their designation as stx 2d1 and stx 2d2 , these opero...

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Section: Discussionmentioning

confidence: 99%

Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

2003

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“…All STEC isolates were also serotyped and their enterohemolytic activity was investigated, and the STEC O157 isolates were phage typed as previously described (12,25,39). Certain single characteristics of 161 strains have been reported previously (12,22,23,24,25,39). Of the 173 strains, 15 were derived from one major outbreak (36) caused by strains of serotype O157:H7:PT2:stx 2 :stx 2c (39).…”

Section: Subjectsmentioning

confidence: 99%

Clinical Escherichia coli Strains Carrying stx Genes: stx Variants and stx -Positive Virulence Profiles

2002

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Altogether, 173 Shiga toxin-producing Escherichia coli (STEC) serotype O157 (n ‫؍‬ 111) and non-O157 (n ‫؍‬ 62) isolates from 170 subjects were screened by PCR-restriction fragment length polymorphism for eight different stx genes. The results were compiled according to serotypes, phage types of O157, production of Stx toxin and enterohemolysin, and the presence of eae. The stx genes occurred in 11 combinations; the most common were stx 2 with stx 2c (42%), stx 2 alone (21%), and stx 1 alone (16%). Of the O157 strains, 64% carried stx 2 with stx 2c versus 2% of the non-O157 strains (P < 0.001). In the non-O157 strains, the prevailing gene was stx 1 (99% versus 1% in O157 strains; P < 0.001). In addition, one strain (O Rough:H4:stx 2c ) which has not previously been described as associated with hemolytic-uremic syndrome (HUS) was found. Ten stx-positive virulence profiles were responsible for 71% of all STEC infections. Of these profiles, five accounted for 71% of the 21 strains isolated from 20 patients with HUS or thrombotic thrombocytopenic purpura (TTP). The strains having the virulence profile that caused mainly HUS or TTP or bloody diarrhea produced Stx with titers of >1:128 (90%) more commonly than did other strains (51%; P < 0.001). These strains were also more commonly enterohemolytic (98% versus 68% for other strains; P < 0.001) and possessed the eae gene (100%) more commonly than did other strains (74%; P < 0.001). A particular virulence profile, O157:H7:PT2:stx 2 :stx 2c :eae: Ehly, was significantly more frequently associated with HUS and bloody diarrhea than were other profiles (P ‫؍‬ 0.02) and also caused the deaths of two children. In this study, the risk factors for severe symptoms were an age of <5 years and infection by the strain of O157:H7:PT2 mentioned above.Shiga toxin-producing Escherichia coli (STEC) cells have emerged as new food-borne pathogens of clinical and public health concern (35). The most epidemic STEC serogroup has been O157, but about 200 other STEC serogroups have been identified (http://www.microbionet.com.au/frames/feature /vtec/brief01.html). Shiga toxins (Stx1 and/or Stx2) have a prominent role in the pathogenesis of STEC bacteria (15,20,26). The clinical picture of a STEC infection may vary from an asymptomatic state to bloody diarrhea and severe life-threatening complications such as hemolytic-uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP) (35). Children and elderly people have been more susceptible to STEC infections than healthy adults (32). It is estimated that the incidence of HUS varies from 2.0 to 3.0 cases per 100,000 children under 5 years of age (15) and from 0.9 to 1.2 cases per 100,000 in children under 18 years of age (5, 43).The pathogenesis of STEC infection in humans is not fully understood. It is considered to be multifactorial and dependent on several bacterial virulence factors such as enterohemolysin (Ehly) and the eae gene, in addition to host factors (6,35). A recent discovery of a quorum-sensing system, mediated by self-produced...

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“…The association between infections with intimin-positive STEC and severe disease in humans was demonstrated previously (13), but it was also shown that intimin is not essential for the virulence of certain STEC strains for humans. Other colonization mechanisms, such as adhesins and pili, were identified in eae-negative strains (58, 75), and certain LEE-negative strains and serotypes of STEC were associated with bloody diarrhea (BD) and HUS (13,14,36). These STEC strains might possess other virulence factors which have not yet been characterized.…”

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Characterization of Shiga Toxin-Producing Escherichia coli Strains Isolated from Human Patients in Germany over a 3-Year Period

et al. 2004

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We have investigated 677 Shiga toxin-producing Escherichia coli (STEC) strains from humans to determine their serotypes, virulence genes, and clinical signs in patients. Six different Shiga toxin types (1, 1c, 2, 2c, 2d, and 2e) were distributed in the STEC strains. Intimin (eae) genes were present in 62.6% of the strains and subtyped into intimins ␣1, ␤1, ␥1, , , and . Shiga toxin types 1c and 2d were present only in eae-negative STEC strains, and type 2 was significantly (P < 0.001) more frequent in eae-positive STEC strains. Enterohemorrhagic E. coli hemolysin was associated with 96.2% of the eae-positive strains and with 65.2% of the eae-negative strains. Clinical signs in the patients were abdominal pain (8.7%), nonbloody diarrhea (59.2%), bloody diarrhea (14.3%), and hemolytic-uremic syndrome (HUS) (3.5%), and 14.3% of the patients had no signs of gastrointestinal disease or HUS. Infections with eae-positive STEC were significantly (P < 0.001) more frequent in children under 6 years of age than in other age groups, whereas eae-negative STEC infections dominated in adults. We identified 41 STEC strains belonging to 31 serotypes which had not previously been described as human STEC. Twenty-six of these were positive for intimins ␣1 (one serotype), ␤1 (eight serotypes), (two serotypes), and (three serotypes). Our study indicates that different types of STEC strains predominate in infant and adult patients and that new types of STEC strains are present among human isolates.The association of Shiga (Vero) toxin production in Escherichia coli with human pathogenicity was first described in 1979 (82, 85). However, it was the investigation of an outbreak caused by Shiga toxin-producing E. coli (STEC) O157 which provided the major impetus to study these pathogens (65). In the following years, STEC strains were increasingly isolated from humans with diarrhea and hemolytic-uremic syndrome (HUS) and from farm animals, which serve as a natural reservoir for STEC (52,86). Today, more than 200 different E. coli O:H serotypes are known to be associated with the production of Shiga toxins (86; K. A. Bettelheim's VTEC table, May 2003 update, www.sciencenet.com.au/vtectable.htm). Certain STEC strains belonging to serogroups O26, O103, O111, O145, and O157 were more frequently isolated from humans with severe diseases such as hemorrhagic colitis and HUS. Accordingly, these highly virulent STEC strains were also designated as enterohemorrhagic E. coli (EHEC) (42, 52). The search for additional virulence markers in these pathogens revealed that most EHEC strains carry a plasmid which encodes a hemolysin (EHEC hemolysin) and the chromosomally located locus of enterocyte effacement (LEE) pathogenicity island (16,43,70,84). The genes carried by the LEE enable the bacteria to produce attaching and effacing lesions in the host intestinal mucosa cells, which increases the virulence of the bacteria for humans (35,44,60). Intimate attachment of bacteria to the host cell is mediated by the binding of intimin, the product of the eae gene...

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Shiga Toxin–ProducingEscherichia coliSerotype OX3:H21 as a Cause of Hemolytic‐Uremic Syndrome

Cited by 32 publications

References 1 publication

Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

Clinical Escherichia coli Strains Carrying stx Genes: stx Variants and stx -Positive Virulence Profiles

Characterization of Shiga Toxin-Producing Escherichia coli Strains Isolated from Human Patients in Germany over a 3-Year Period

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Shiga Toxin–ProducingEscherichia coliSerotype OX3:H21 as a Cause of Hemolytic‐Uremic Syndrome

Cited by 32 publications

References 1 publication

Presence of Activatable Shiga Toxin Genotype ( stx 2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

Presence of Activatable Shiga Toxin Genotype ( stx 2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

Clinical Escherichia coli Strains Carrying stx Genes: stx Variants and stx -Positive Virulence Profiles

Characterization of Shiga Toxin-Producing Escherichia coli Strains Isolated from Human Patients in Germany over a 3-Year Period

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Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources

Presence of Activatable Shiga Toxin Genotype ( stx _2d ) in Shiga Toxigenic Escherichia coli from Livestock Sources