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- Hua, Y., et al.
(author)
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Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden
- 2020
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In: Emerging microbes & infections. - : Informa UK Limited. - 2222-1751. ; 9:1, s. 2562-2570
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Journal article (peer-reviewed)abstract
- Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause a wide range of symptoms from asymptomatic carriage, mild diarrhea to bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Intimin, encoded by the eae gene, also plays a critical role in STEC pathogenesis. Herein, we investigated the prevalence and genetic diversity of eae among clinical STEC isolates from patients with diarrhea, BD, HUS as well as from asymptomatic STEC-positive individuals in Sweden with whole-genome sequencing. We found that 173 out of 239 (72.4%) of clinical STEC strains were eae positive. Six eae subtypes (epsilon 1, gamma 1, beta 3, theta, zeta and rho) were identified eae and its subtype gamma 1 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. epsilon 1 was associated with O121:H19 and O103:H2 strains, and beta 3 to O26:H11 strains. The combination of eae subtype gamma 1 and stx subtype (stx (2) or stx (1)+stx (2)) is more likely to cause severe disease, suggesting the possibility of using eae genotypes in risk assessment of STEC infection. In summary, this study demonstrated a high prevalence of eae in clinical STEC strains and considerable genetic diversity of eae in STEC strains in Sweden from 1994 through 2018, and revealed association between eae subtypes and disease severity.
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- Hua, Y., et al.
(author)
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Molecular Characterization of the Enterohemolysin Gene (ehxA) in Clinical Shiga Toxin-Producing Escherichia coli Isolates
- 2021
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In: Toxins. - : MDPI AG. - 2072-6651. ; 13:1
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Journal article (peer-reviewed)abstract
- Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx(2a) + stx(2c) (p < 0.001) and eae (p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae-positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group ? (ehxA subtype A), group II (ehxA subtype B, C, and F), and group (ehxA subtype D). Most BD- and HUS-associated isolates were clustered into ehxA group II, while ehxA group ? was associated with non-bloody stool and individuals >= 10 years of age. The presence of ehxA + eae and ehxA + eae + stx(2) was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group II) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA, together with stx and eae, can be used as a risk predictor for HUS in STEC infections.
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- Hua, Y., et al.
(author)
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Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden
- 2021
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In: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 12:1, s. 1296-1305
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Journal article (peer-reviewed)abstract
- Shiga toxin-producing Escherichia coli, a foodborne bacterial pathogen, has been linked to a broad spectrum of clinical outcomes ranging from asymptomatic carriage to fatal hemolytic uremic syndrome (HUS). Here, we collected clinical data and STEC strains from HUS patients from 1994 through 2018, whole-genome sequencing was performed to molecularly characterize HUS-associated STEC strains, statistical analysis was conducted to identify bacterial genetic factors associated with severe outcomes in HUS patients. O157:H7 was the most predominant serotype (57%) among 54 HUS-associated STEC strains, followed by O121:H19 (19%) and O26:H11 (7%). Notably, some non-predominant serotypes such as O59:H17 (2%) and O109:H21 (2%) also caused HUS. All O157:H7 strains with one exception belonged to clade 8. During follow-up at a median of 4years, 41% of the patients had renal sequelae. Fifty-nine virulence genes were found to be statistically associated with severe renal sequelae, these genes encoded type II and type III secretion system effectors, chaperones, and other factors. Notably, virulence genes associated with severe clinical outcomes were significantly more prevalent in O157:H7 strains. In contrast, genes related to mild symptoms were evenly distributed across all serotypes. The whole-genome phylogeny indicated high genomic diversity among HUS-STEC strains. No distinct cluster was found between HUS and non-HUS STEC strains. The current study showed that O157:H7 remains the main cause of STEC-associated HUS, despite the rising importance of other non-O157 serotypes. Besides, O157:H7 is associated with severe renal sequelae in the follow-up, which could be a risk factor for long-term prognosis in HUS patients. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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- Matussek, Andreas, et al.
(author)
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Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994-2018
- 2023
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In: European Journal of Clinical Microbiology and Infectious Diseases. - 0934-9723 .- 1435-4373. ; 42, s. 771-779
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Journal article (peer-reviewed)abstract
- Shiga toxin-producing Escherichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene (stx) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a + stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin (eae) and its receptor (tir), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.
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