Virulence Factors for Hemolytic Uremic Syndrome, Denmark1

Ethelberg, Steen; Olsen, Katharina E. P.; Scheutz, Flemming; Jensen, Charlotte; Schiellerup, Peter; Engberg, Jørgen; Petersen, Andreas Munk; Olesen, Bente; Gerner‐Smidt, Peter; Mølbak, Kåre

doi:10.3201/eid1005.030576

Cited by 239 publications

(202 citation statements)

References 13 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…It is also clear that host E. coli genetics influence pathogenic potential, and STEC strains which lack intestinal colonization Originally, clinical disease due to STEC was predominantly associated with E. coli serotype O157:H7. It is clear that, for E. coli strains with the fairly consistent O157:H7 genetic background, humans infected with isolates that produce Stx2a are more likely to develop life-threatening disease than individuals infected with isolates that produce Stx1 (2,12,24,40,41). However, even the pathogenic potentials of Stx2a-producing O157:H7 strains can differ (8,36).…”

Section: Discussionmentioning

confidence: 99%

“…6). The relative lack of potency for Stx2c in all three toxicity assays is puzzling, since Stx2c has been reported to be associated with HUS (12,16,33,44). However, there is some confusion in the literature: sequences deposited in GenBank as Stx2c would be unambiguously classified as Stx2d using the designations adopted in 2009 (15).…”

Section: Discussionmentioning

confidence: 99%

“…Stx includes two major antigenic forms (Stx1 and Stx2) (54), which share approximately 60% amino acid identity. Epidemiological studies suggest that Stx2 is more often associated with severe disease and development of HUS than Stx1 (2,12,17,24,40,41). Studies in primates have shown that administration of Stx2 alone can produce the symptoms of HUS, while administration of Stx1 at the same dose does not cause HUS (50,53).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Shiga Toxin Subtypes Display Dramatic Differences in Potency

et al. 2011

View full text Add to dashboard Cite

Purified Shiga toxin (Stx) alone is capable of producing systemic complications, including hemolytic-uremic syndrome (HUS), in animal models of disease. Stx includes two major antigenic forms (Stx1 and Stx2), with minor variants of Stx2 (Stx2a to -h). Stx2a is more potent than Stx1. Epidemiologic studies suggest that Stx2 subtypes also differ in potency, but these differences have not been well documented for purified toxin. The relative potencies of five purified Stx2 subtypes, Stx2a, Stx2b, Stx2c, Stx2d, and activated (elastase-cleaved) Stx2d, were studied in vitro by examining protein synthesis inhibition using Vero monkey kidney cells and inhibition of metabolic activity (reduction of resazurin to fluorescent resorufin) using primary human renal proximal tubule epithelial cells (RPTECs). In both RPTECs and Vero cells, Stx2a, Stx2d, and elastase-cleaved Stx2d were at least 25 times more potent than Stx2b and Stx2c. In vivo potency in mice was also assessed. Stx2b and Stx2c had potencies similar to that of Stx1, while Stx2a, Stx2d, and elastase-cleaved Stx2d were 40 to 400 times more potent than Stx1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Shiga Toxin Subtypes Display Dramatic Differences in Potency

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Stx2 has been associated with severe disease more frequently than Stx1 (Boerlin et al, 1999;Ethelberg et al, 2004), and was shown to be 400 times more potent than Stx1, in mice (Tesh et al, 1993). Mitomycin C treatment also led to increased induction of stx2 expression in TW14359 compared to Sakai (Kulasekara et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

et al. 2010

View full text Add to dashboard Cite

The Escherichia coli O157 : H7 TW14359 strain was implicated in a multi-state outbreak in North America in 2006, which resulted in high rates of severe disease. Similarly, the O157 : H7 RIMD0509952 (Sakai) strain caused the largest O157 : H7 outbreak to date. Both strains were shown to represent divergent phylogenetic lineages. Here we compared global gene expression patterns before and after epithelial cell exposure, as well as the ability to adhere to and invade epithelial cells, between the two outbreak strains. Epithelial cell assays demonstrated a 2.5-fold greater adherence of the TW14359 strain relative to Sakai, while whole-genome microarrays detected significant differential expression of 914 genes, 206 of which had a fold change ≥1.5. Interestingly, most locus of enterocyte effacement (LEE) genes were upregulated in TW14359, whereas flagellar and chemotaxis genes were primarily upregulated in Sakai, suggesting discordant expression of these genes between the two strains. The Shiga toxin 2 genes were also upregulated in the TW14359 strain, as were several pO157-encoded genes that promote adherence, including type II secretion genes and their effectors stcE and adfO. Quantitative RT-PCR confirmed the expression differences detected in the microarray analysis, and expression levels were lower for a subset of LEE genes before versus after exposure to epithelial cells. In all, this study demonstrated the upregulation of major and ancillary virulence genes in TW14359 and of flagellar and chemotaxis genes in Sakai, under conditions that precede intimate bacterial attachment to epithelial cells. Differences in the level of adherence to epithelial cells were also observed, implying that these two phylogenetically divergent O157 : H7 outbreak strains vary in their ability to colonize, or initiate the disease process.

show abstract

“…They are associated with a wide spectrum of disease ranging from mild to bloody diarrhoea, through to haemorrhagic colitis and haemolytic uraemic syndrome (HUS) (1) The primary STEC virulence factor responsible for the most serious outcomes of human infection is Shiga toxin (Stx), an AB5 toxin that targets cells expressing the glycolipid globotriaosylceramide (Gb3), disrupting host protein synthesis and causing apoptotic cell death (2). Renal epithelial cell membranes are enriched for Gb3 resulting in the kidneys bearing the brunt of Stx toxicity and, in 5-10% of cases, this leads to the development of Hemolytic Uremic Syndrome (HUS) (1).…”

Section: Introductionmentioning

confidence: 99%

Insight into Shiga toxin genes encoded by Escherichia coli O157 from whole genome sequencing

Ashton

Perry

Ellis

et al. 2014

Preprint

View full text Add to dashboard Cite

The ability of Shiga toxin-producing Escherichia coli (STEC) to cause severe illness in humans is determined by multiple host factors and bacterial characteristics, including Shiga toxin (Stx) subtype. Given the link between Stx2a subtype and disease severity, we sought to identify the stx subtypes present in whole genome sequences (WGS) of 444 isolates of STEC O157. Difficulties in assembling the stx genes in some strains, were overcome by using two complementary bioinformatics methods; mapping and de novo assembly. We compared the WGS analysis with the results obtained using a PCR approach and investigated the diversity within and between the subtypes. All strains of STEC O157 in this study had stx1a, stx2a or stx2c or a combination of these three genes. There was over 99% (442/444) concordance between PCR and WGS. When common source strains were excluded, 236/349 strains of STEC O157 had multiple copies of different Stx subtypes and 54 had multiple copies of the same Stx subtype. Of those strains harbouring multiple copies of the same Stx subtype, 33 had variants between the alleles while 21 had identical copies. Strains harbouring Stx2a only were most commonly found to have multiple alleles of the same subtype (42%). Both the PCR and WGS approach to stx subtyping provided a good level of sensitivity and specificity. In addition, the WGS data also showed there were a significant proportion of strains harbouring multiple alleles of the same Stx subtype associated with clinical disease in England. PrePrints AbstractThe ability of Shiga toxin-producing Escherichia coli (STEC) to cause severe illness in humans is determined by multiple host factors and bacterial characteristics, including Shiga toxin (Stx) subtype. Given the link between Stx2a subtype and disease severity, we sought to identify the stx subtypes present in whole genome sequences (WGS) of 444 isolates of STEC O157. Difficulties in assembling the stx genes in some strains, were overcome by using two complementary bioinformatics methods; mapping and de novo assembly. We compared the WGS analysis with the results obtained using a PCR approach and investigated the diversity within and between the subtypes. All strains of STEC O157 in this study had stx1a, stx2a or stx2c or a combination of these three genes. There was over 99% (442/444) concordance between PCR and WGS. When common source strains were excluded, 236/349 strains of STEC O157 had multiple copies of different Stx subtypes and 54 had multiple copies of the same Stx subtype. Of those strains harbouring multiple copies of the same Stx subtype, 33 had variants between the alleles while 21 had identical copies. Strains harbouring Stx2a only were most commonly found to have multiple alleles of the same subtype (42%). Both the PCR and WGS approach to stx subtyping provided a good level of sensitivity and specificity. In addition, the WGS data also showed there were a significant proportion of strains harbouring multiple alleles of the same Stx subtype associated with clinical disease in England.

show abstract

Virulence Factors for Hemolytic Uremic Syndrome, Denmark1

Cited by 239 publications

References 13 publications

Shiga Toxin Subtypes Display Dramatic Differences in Potency

Shiga Toxin Subtypes Display Dramatic Differences in Potency

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

Insight into Shiga toxin genes encoded by Escherichia coli O157 from whole genome sequencing

Contact Info

Product

Resources

About