Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157

ABSTRACT Foodborne infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of diarrheal illness in humans and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food chain through contami...

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Autores principales: Daniel H. Stones, Alexander G. J. Fehr, Laurel Thompson, Jacqueline Rocha, Nicolas Perez-Soto, Vipin T. P. Madhavan, Kerstin Voelz, Anne Marie Krachler
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Publicado: American Society for Microbiology 2017
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spelling oai:doaj.org-article:78b7931a3a8f4b148433f87779e575122021-11-15T15:22:05ZZebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O15710.1128/mSphereDirect.00365-172379-5042https://doaj.org/article/78b7931a3a8f4b148433f87779e575122017-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00365-17https://doaj.org/toc/2379-5042ABSTRACT Foodborne infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of diarrheal illness in humans and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food chain through contaminated meat, dairy, or vegetables. Here, we describe the establishment of a vertebrate model for foodborne EHEC infection, using larval zebrafish (Danio rerio) as a host and the protozoan prey Paramecium caudatum as a vehicle. We follow pathogen release from the vehicle, intestinal colonization, microbe-host interactions, and microbial gene induction within a live vertebrate host, in real time, throughout the course of infection. We demonstrate that foodborne EHEC colonizes the gastrointestinal tract faster and establishes a higher burden than waterborne infection. Expression of the locus of enterocyte effacement (LEE), a key EHEC virulence factor, was observed early during infection, mainly at sites that experience fluid shear, and required tight control to enable successful host colonization. EHEC infection led to strain- and LEE-dependent mortality in the zebrafish host. Despite the presence of the endogenous microbiota limiting EHEC colonization levels, EHEC colonization and virulence can be studied either under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, we show that the model can be used for investigation of factors affecting shedding and transmission of bacteria to naive hosts. Overall, this constitutes a useful model, which ideally complements the strengths of existing EHEC vertebrate models. IMPORTANCE Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen which can cause diarrhea, vomiting, and, in some cases, severe complications such as kidney failure in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food chain through contaminated meat, dairy, and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence, and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study foodborne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Our results show that foodborne infection is more efficient than waterborne infection and that the locus of enterocyte effacement is a key virulence determinant in the zebrafish model. It is induced early during infection, and loss of tight LEE regulation leads to a decreased bacterial burden and decreased host mortality. Overall, the zebrafish model allows us to study foodborne infection, including pathogen release from the food vehicle and gene regulation and its context of host-microbe interactions, as well as environmental shedding and transmission to naive hosts.Daniel H. StonesAlexander G. J. FehrLaurel ThompsonJacqueline RochaNicolas Perez-SotoVipin T. P. MadhavanKerstin VoelzAnne Marie KrachlerAmerican Society for MicrobiologyarticleEHECO157foodborne pathogensgastrointestinal infectioninfection modelintravital imagingMicrobiologyQR1-502ENmSphere, Vol 2, Iss 5 (2017)
institution DOAJ
collection DOAJ
language EN
topic EHEC
O157
foodborne pathogens
gastrointestinal infection
infection model
intravital imaging
Microbiology
QR1-502
spellingShingle EHEC
O157
foodborne pathogens
gastrointestinal infection
infection model
intravital imaging
Microbiology
QR1-502
Daniel H. Stones
Alexander G. J. Fehr
Laurel Thompson
Jacqueline Rocha
Nicolas Perez-Soto
Vipin T. P. Madhavan
Kerstin Voelz
Anne Marie Krachler
Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
description ABSTRACT Foodborne infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of diarrheal illness in humans and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food chain through contaminated meat, dairy, or vegetables. Here, we describe the establishment of a vertebrate model for foodborne EHEC infection, using larval zebrafish (Danio rerio) as a host and the protozoan prey Paramecium caudatum as a vehicle. We follow pathogen release from the vehicle, intestinal colonization, microbe-host interactions, and microbial gene induction within a live vertebrate host, in real time, throughout the course of infection. We demonstrate that foodborne EHEC colonizes the gastrointestinal tract faster and establishes a higher burden than waterborne infection. Expression of the locus of enterocyte effacement (LEE), a key EHEC virulence factor, was observed early during infection, mainly at sites that experience fluid shear, and required tight control to enable successful host colonization. EHEC infection led to strain- and LEE-dependent mortality in the zebrafish host. Despite the presence of the endogenous microbiota limiting EHEC colonization levels, EHEC colonization and virulence can be studied either under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, we show that the model can be used for investigation of factors affecting shedding and transmission of bacteria to naive hosts. Overall, this constitutes a useful model, which ideally complements the strengths of existing EHEC vertebrate models. IMPORTANCE Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen which can cause diarrhea, vomiting, and, in some cases, severe complications such as kidney failure in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food chain through contaminated meat, dairy, and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence, and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study foodborne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Our results show that foodborne infection is more efficient than waterborne infection and that the locus of enterocyte effacement is a key virulence determinant in the zebrafish model. It is induced early during infection, and loss of tight LEE regulation leads to a decreased bacterial burden and decreased host mortality. Overall, the zebrafish model allows us to study foodborne infection, including pathogen release from the food vehicle and gene regulation and its context of host-microbe interactions, as well as environmental shedding and transmission to naive hosts.
format article
author Daniel H. Stones
Alexander G. J. Fehr
Laurel Thompson
Jacqueline Rocha
Nicolas Perez-Soto
Vipin T. P. Madhavan
Kerstin Voelz
Anne Marie Krachler
author_facet Daniel H. Stones
Alexander G. J. Fehr
Laurel Thompson
Jacqueline Rocha
Nicolas Perez-Soto
Vipin T. P. Madhavan
Kerstin Voelz
Anne Marie Krachler
author_sort Daniel H. Stones
title Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
title_short Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
title_full Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
title_fullStr Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
title_full_unstemmed Zebrafish (<named-content content-type="genus-species">Danio rerio</named-content>) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne <named-content content-type="genus-species">Escherichia coli</named-content> O157
title_sort zebrafish (<named-content content-type="genus-species">danio rerio</named-content>) as a vertebrate model host to study colonization, pathogenesis, and transmission of foodborne <named-content content-type="genus-species">escherichia coli</named-content> o157
publisher American Society for Microbiology
publishDate 2017
url https://doaj.org/article/78b7931a3a8f4b148433f87779e57512
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