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First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model

Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both...

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Autores principales: Bauer, Tobias, Sipos, Wolfgang, Stark, Timo D., Käser, Tobias, Knecht, Christian, Brunthaler, Rene, Saalmüller, Armin, Hofmann, Thomas, Ehling-Schulz, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234764/
https://www.ncbi.nlm.nih.gov/pubmed/30464760
http://dx.doi.org/10.3389/fmicb.2018.02652
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author Bauer, Tobias
Sipos, Wolfgang
Stark, Timo D.
Käser, Tobias
Knecht, Christian
Brunthaler, Rene
Saalmüller, Armin
Hofmann, Thomas
Ehling-Schulz, Monika
author_facet Bauer, Tobias
Sipos, Wolfgang
Stark, Timo D.
Käser, Tobias
Knecht, Christian
Brunthaler, Rene
Saalmüller, Armin
Hofmann, Thomas
Ehling-Schulz, Monika
author_sort Bauer, Tobias
collection PubMed
description Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg(-1) body weight to study acute effects or using daily doses of 10 μg cereulide kg(-1) body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations.
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spelling pubmed-62347642018-11-21 First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model Bauer, Tobias Sipos, Wolfgang Stark, Timo D. Käser, Tobias Knecht, Christian Brunthaler, Rene Saalmüller, Armin Hofmann, Thomas Ehling-Schulz, Monika Front Microbiol Microbiology Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg(-1) body weight to study acute effects or using daily doses of 10 μg cereulide kg(-1) body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations. Frontiers Media S.A. 2018-11-07 /pmc/articles/PMC6234764/ /pubmed/30464760 http://dx.doi.org/10.3389/fmicb.2018.02652 Text en Copyright © 2018 Bauer, Sipos, Stark, Käser, Knecht, Brunthaler, Saalmüller, Hofmann and Ehling-Schulz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Bauer, Tobias
Sipos, Wolfgang
Stark, Timo D.
Käser, Tobias
Knecht, Christian
Brunthaler, Rene
Saalmüller, Armin
Hofmann, Thomas
Ehling-Schulz, Monika
First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title_full First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title_fullStr First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title_full_unstemmed First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title_short First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model
title_sort first insights into within host translocation of the bacillus cereus toxin cereulide using a porcine model
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234764/
https://www.ncbi.nlm.nih.gov/pubmed/30464760
http://dx.doi.org/10.3389/fmicb.2018.02652
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