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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/210365
Ver los metadatos del registro completo
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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 |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.22299 |