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Published in: Gut Pathogens 1/2017

Open Access 01-12-2017 | Research

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

Authors: Bettina Wöchtl, Florian Gunzer, Wilhelm Gerner, Hagen Gasse, Michaela Koch, Zoltán Bagó, Martin Ganter, Herbert Weissenböck, Nora Dinhopl, Sina M. Coldewey, Alexandra von Altrock, Karl-Heinz Waldmann, Armin Saalmüller, Kurt Zimmermann, Jörg Steinmann, Jan Kehrmann, Ludger Klein-Hitpass, Jochen Blom, Ralf Ehricht, Ines Engelmann, Isabel Hennig-Pauka

Published in: Gut Pathogens | Issue 1/2017

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Abstract

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.
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Metadata
Title
Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7
Authors
Bettina Wöchtl
Florian Gunzer
Wilhelm Gerner
Hagen Gasse
Michaela Koch
Zoltán Bagó
Martin Ganter
Herbert Weissenböck
Nora Dinhopl
Sina M. Coldewey
Alexandra von Altrock
Karl-Heinz Waldmann
Armin Saalmüller
Kurt Zimmermann
Jörg Steinmann
Jan Kehrmann
Ludger Klein-Hitpass
Jochen Blom
Ralf Ehricht
Ines Engelmann
Isabel Hennig-Pauka
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2017
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-017-0179-8

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