Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease

Autores
Nyblade, Charlotte; Parreño, Gladys Viviana; Zhou, Peng; Hensley, Casey; Oakes, Vanessa; Mahsoub, Hassan M.; Kiley, Kelsey; Frazier, Maggie; Frazier, Annie; Zhang, Yongrong; Feng, Hanping; Yuan, Lijuan
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.
Fil: Nyblade, Charlotte. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Zhou, Peng. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Hensley, Casey. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Oakes, Vanessa. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Mahsoub, Hassan M.. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Kiley, Kelsey. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Frazier, Maggie. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Frazier, Annie. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Zhang, Yongrong. University of Maryland; Estados Unidos
Fil: Feng, Hanping. University of Maryland; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute And State University; Estados Unidos
Materia
CLOSTRIDIOIDES DIFFICILE INFECTION/ILLNESS (CDI)
GNOTOBIOTIC PIGS
PSEUDOMEMBRANOUS COLITIS (PMC)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/210365
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/210365
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Establishment of a gnotobiotic pig model of Clostridioides difficile infection and diseaseNyblade, CharlotteParreño, Gladys VivianaZhou, PengHensley, CaseyOakes, VanessaMahsoub, Hassan M.Kiley, KelseyFrazier, MaggieFrazier, AnnieZhang, YongrongFeng, HanpingYuan, LijuanCLOSTRIDIOIDES DIFFICILE INFECTION/ILLNESS (CDI)GNOTOBIOTIC PIGSPSEUDOMEMBRANOUS COLITIS (PMC)https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.Fil: Nyblade, Charlotte. Virginia Polytechnic Institute And State University; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Zhou, Peng. Virginia Polytechnic Institute And State University; Estados UnidosFil: Hensley, Casey. Virginia Polytechnic Institute And State University; Estados UnidosFil: Oakes, Vanessa. Virginia Polytechnic Institute And State University; Estados UnidosFil: Mahsoub, Hassan M.. Virginia Polytechnic Institute And State University; Estados UnidosFil: Kiley, Kelsey. Virginia Polytechnic Institute And State University; Estados UnidosFil: Frazier, Maggie. Virginia Polytechnic Institute And State University; Estados UnidosFil: Frazier, Annie. Virginia Polytechnic Institute And State University; Estados UnidosFil: Zhang, Yongrong. University of Maryland; Estados UnidosFil: Feng, Hanping. University of Maryland; Estados UnidosFil: Yuan, Lijuan. Virginia Polytechnic Institute And State University; Estados UnidosBioMed Central2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/210365Nyblade, Charlotte; Parreño, Gladys Viviana; Zhou, Peng; Hensley, Casey; Oakes, Vanessa; et al.; Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease; BioMed Central; Gut Pathogens; 14; 1; 12-2022; 1-101757-4749CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s13099-022-00496-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:49:25Zoai:ri.conicet.gov.ar:11336/210365instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:49:25.659CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
title Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
spellingShingle Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
Nyblade, Charlotte
CLOSTRIDIOIDES DIFFICILE INFECTION/ILLNESS (CDI)
GNOTOBIOTIC PIGS
PSEUDOMEMBRANOUS COLITIS (PMC)
title_short Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
title_full Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
title_fullStr Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
title_full_unstemmed Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
title_sort Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
dc.creator.none.fl_str_mv Nyblade, Charlotte
Parreño, Gladys Viviana
Zhou, Peng
Hensley, Casey
Oakes, Vanessa
Mahsoub, Hassan M.
Kiley, Kelsey
Frazier, Maggie
Frazier, Annie
Zhang, Yongrong
Feng, Hanping
Yuan, Lijuan
author Nyblade, Charlotte
author_facet Nyblade, Charlotte
Parreño, Gladys Viviana
Zhou, Peng
Hensley, Casey
Oakes, Vanessa
Mahsoub, Hassan M.
Kiley, Kelsey
Frazier, Maggie
Frazier, Annie
Zhang, Yongrong
Feng, Hanping
Yuan, Lijuan
author_role author
author2 Parreño, Gladys Viviana
Zhou, Peng
Hensley, Casey
Oakes, Vanessa
Mahsoub, Hassan M.
Kiley, Kelsey
Frazier, Maggie
Frazier, Annie
Zhang, Yongrong
Feng, Hanping
Yuan, Lijuan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CLOSTRIDIOIDES DIFFICILE INFECTION/ILLNESS (CDI)
GNOTOBIOTIC PIGS
PSEUDOMEMBRANOUS COLITIS (PMC)
topic CLOSTRIDIOIDES DIFFICILE INFECTION/ILLNESS (CDI)
GNOTOBIOTIC PIGS
PSEUDOMEMBRANOUS COLITIS (PMC)
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.
Fil: Nyblade, Charlotte. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Zhou, Peng. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Hensley, Casey. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Oakes, Vanessa. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Mahsoub, Hassan M.. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Kiley, Kelsey. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Frazier, Maggie. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Frazier, Annie. Virginia Polytechnic Institute And State University; Estados Unidos
Fil: Zhang, Yongrong. University of Maryland; Estados Unidos
Fil: Feng, Hanping. University of Maryland; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute And State University; Estados Unidos
description Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/210365
Nyblade, Charlotte; Parreño, Gladys Viviana; Zhou, Peng; Hensley, Casey; Oakes, Vanessa; et al.; Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease; BioMed Central; Gut Pathogens; 14; 1; 12-2022; 1-10
1757-4749
CONICET Digital
CONICET
url http://hdl.handle.net/11336/210365
identifier_str_mv Nyblade, Charlotte; Parreño, Gladys Viviana; Zhou, Peng; Hensley, Casey; Oakes, Vanessa; et al.; Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease; BioMed Central; Gut Pathogens; 14; 1; 12-2022; 1-10
1757-4749
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s13099-022-00496-y
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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