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Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7
BACKGROUND: Shiga toxin (Stx) producing Escherichia coli (E. coli) (STEC) is the most frequent cause of diarrhoea-positive haemolytic uraemic syndrome (D + HUS) in humans. In 2011, a huge outbreak with an STEC O104:H4 strain in Germany highlighted the limited possibilities for causative treatment of...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445466/ https://www.ncbi.nlm.nih.gov/pubmed/28559930 http://dx.doi.org/10.1186/s13099-017-0179-8 |
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author | Wöchtl, Bettina Gunzer, Florian Gerner, Wilhelm Gasse, Hagen Koch, Michaela Bagó, Zoltán Ganter, Martin Weissenböck, Herbert Dinhopl, Nora Coldewey, Sina M. von Altrock, Alexandra Waldmann, Karl-Heinz Saalmüller, Armin Zimmermann, Kurt Steinmann, Jörg Kehrmann, Jan Klein-Hitpass, Ludger Blom, Jochen Ehricht, Ralf Engelmann, Ines Hennig-Pauka, Isabel |
author_facet | Wöchtl, Bettina Gunzer, Florian Gerner, Wilhelm Gasse, Hagen Koch, Michaela Bagó, Zoltán Ganter, Martin Weissenböck, Herbert Dinhopl, Nora Coldewey, Sina M. von Altrock, Alexandra Waldmann, Karl-Heinz Saalmüller, Armin Zimmermann, Kurt Steinmann, Jörg Kehrmann, Jan Klein-Hitpass, Ludger Blom, Jochen Ehricht, Ralf Engelmann, Ines Hennig-Pauka, Isabel |
author_sort | Wöchtl, Bettina |
collection | PubMed |
description | BACKGROUND: Shiga toxin (Stx) producing Escherichia coli (E. coli) (STEC) is the most frequent cause of diarrhoea-positive haemolytic uraemic syndrome (D + HUS) in humans. In 2011, a huge outbreak with an STEC O104:H4 strain in Germany highlighted the limited possibilities for causative treatment of this syndrome. The responsible STEC strain was found to combine Stx production with adherence mechanisms normally found in enteroaggregative E. coli (EAEC). Pathotypes of E. coli evolve and can exhibit different adhesion mechanisms. It has been shown previously that neonatal gnotobiotic piglets are susceptible for infection with STEC, such as STEC O157:H7 as well as for EAEC, which are considered to be the phylogenetic origin of E. coli O104:H4. This study was designed to characterise the host response to infection with the STEC O104:H4 outbreak strain in comparison to an STEC O157:H7 isolate by evaluating clinical parameters (scoring) and markers of organ dysfunction (biochemistry), as well as immunological (flow cytometry, assessment of cytokines/chemokines and acute phase proteins) and histological alterations (light- and electron microscopy) in a gnotobiotic piglet model of haemolytic uraemic syndrome. RESULTS: We observed severe clinical symptoms, such as diarrhoea, dehydration and neurological disorders as well as attaching-and-effacing lesions (A/E) in the colon in STEC O157:H7 infected piglets. In contrast, STEC O104:H4 challenged animals exhibited only mild clinical symptoms including diarrhoea and dehydration and HUS-specific/severe histopathological, haematological and biochemical alterations were only inconsistently presented by individual piglets. A specific adherence phenotype of STEC O104:H4 could not be observed. Flow cytometric analyses of lymphocytes derived from infected animals revealed an increase of natural killer cells (NK cells) during the course of infection revealing a potential role of this subset in the anti-bacterial activity in STEC disease. CONCLUSIONS: Unexpectedly, E. coli O104:H4 infection caused only mild symptoms and minor changes in histology and blood parameters in piglets. Outcome of the infection trial does not reflect E. coli O104:H4 associated human disease as observed during the outbreak in 2011. The potential role of cells of the innate immune system for STEC related disease pathogenesis should be further elucidated. |
format | Online Article Text |
id | pubmed-5445466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54454662017-05-30 Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 Wöchtl, Bettina Gunzer, Florian Gerner, Wilhelm Gasse, Hagen Koch, Michaela Bagó, Zoltán Ganter, Martin Weissenböck, Herbert Dinhopl, Nora Coldewey, Sina M. von Altrock, Alexandra Waldmann, Karl-Heinz Saalmüller, Armin Zimmermann, Kurt Steinmann, Jörg Kehrmann, Jan Klein-Hitpass, Ludger Blom, Jochen Ehricht, Ralf Engelmann, Ines Hennig-Pauka, Isabel Gut Pathog Research BACKGROUND: Shiga toxin (Stx) producing Escherichia coli (E. coli) (STEC) is the most frequent cause of diarrhoea-positive haemolytic uraemic syndrome (D + HUS) in humans. In 2011, a huge outbreak with an STEC O104:H4 strain in Germany highlighted the limited possibilities for causative treatment of this syndrome. The responsible STEC strain was found to combine Stx production with adherence mechanisms normally found in enteroaggregative E. coli (EAEC). Pathotypes of E. coli evolve and can exhibit different adhesion mechanisms. It has been shown previously that neonatal gnotobiotic piglets are susceptible for infection with STEC, such as STEC O157:H7 as well as for EAEC, which are considered to be the phylogenetic origin of E. coli O104:H4. This study was designed to characterise the host response to infection with the STEC O104:H4 outbreak strain in comparison to an STEC O157:H7 isolate by evaluating clinical parameters (scoring) and markers of organ dysfunction (biochemistry), as well as immunological (flow cytometry, assessment of cytokines/chemokines and acute phase proteins) and histological alterations (light- and electron microscopy) in a gnotobiotic piglet model of haemolytic uraemic syndrome. RESULTS: We observed severe clinical symptoms, such as diarrhoea, dehydration and neurological disorders as well as attaching-and-effacing lesions (A/E) in the colon in STEC O157:H7 infected piglets. In contrast, STEC O104:H4 challenged animals exhibited only mild clinical symptoms including diarrhoea and dehydration and HUS-specific/severe histopathological, haematological and biochemical alterations were only inconsistently presented by individual piglets. A specific adherence phenotype of STEC O104:H4 could not be observed. Flow cytometric analyses of lymphocytes derived from infected animals revealed an increase of natural killer cells (NK cells) during the course of infection revealing a potential role of this subset in the anti-bacterial activity in STEC disease. CONCLUSIONS: Unexpectedly, E. coli O104:H4 infection caused only mild symptoms and minor changes in histology and blood parameters in piglets. Outcome of the infection trial does not reflect E. coli O104:H4 associated human disease as observed during the outbreak in 2011. The potential role of cells of the innate immune system for STEC related disease pathogenesis should be further elucidated. BioMed Central 2017-05-25 /pmc/articles/PMC5445466/ /pubmed/28559930 http://dx.doi.org/10.1186/s13099-017-0179-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Wöchtl, Bettina Gunzer, Florian Gerner, Wilhelm Gasse, Hagen Koch, Michaela Bagó, Zoltán Ganter, Martin Weissenböck, Herbert Dinhopl, Nora Coldewey, Sina M. von Altrock, Alexandra Waldmann, Karl-Heinz Saalmüller, Armin Zimmermann, Kurt Steinmann, Jörg Kehrmann, Jan Klein-Hitpass, Ludger Blom, Jochen Ehricht, Ralf Engelmann, Ines Hennig-Pauka, Isabel Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title | Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title_full | Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title_fullStr | Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title_full_unstemmed | Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title_short | Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7 |
title_sort | comparison of clinical and immunological findings in gnotobiotic piglets infected with escherichia coli o104:h4 outbreak strain and ehec o157:h7 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445466/ https://www.ncbi.nlm.nih.gov/pubmed/28559930 http://dx.doi.org/10.1186/s13099-017-0179-8 |
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