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.
Instituto de Virología
Fil: Nyblade, Charlotte. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Parreño, Gladys Viviana. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhou, Peng. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Hensley, Casey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Oakes, Vanessa. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; Estados Unidos
Fil: Kiley, Kelsey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Maggie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Annie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhang, Yongrong. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados Unidos
Fil: Feng, Hanping. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; Estados Unidos
Fuente
Gut Pathogens 14 : 22 (Junio 2022)
Materia
Gnotobiotic Animals
Swine
Animales Notobióticos
Cerdo
Clostridioides difficile
Pseudomembranous colitis
Colitis pseudomembranosa
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/12350
Acceder
id INTADig_caabd47e08f713bf84befe77096e8b69
oai_identifier_str oai:localhost:20.500.12123/12350
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
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, LijuanGnotobiotic AnimalsSwineAnimales NotobióticosCerdoClostridioides difficilePseudomembranous colitisColitis pseudomembranosaClostridioides 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.Instituto de VirologíaFil: Nyblade, Charlotte. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parreño, Gladys Viviana. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Zhou, Peng. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Hensley, Casey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Oakes, Vanessa. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; Estados UnidosFil: Kiley, Kelsey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Maggie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Annie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Zhang, Yongrong. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados UnidosFil: Feng, Hanping. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados UnidosFil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; Estados UnidosBioMed Central2022-07-19T16:32:40Z2022-07-19T16:32:40Z2022-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/12350https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-022-00496-y1757-4749https://doi.org/10.1186/s13099-022-00496-yGut Pathogens 14 : 22 (Junio 2022)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-10-16T09:30:48Zoai:localhost:20.500.12123/12350instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-16 09:30:49.616INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
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
Gnotobiotic Animals
Swine
Animales Notobióticos
Cerdo
Clostridioides difficile
Pseudomembranous colitis
Colitis pseudomembranosa
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 Gnotobiotic Animals
Swine
Animales Notobióticos
Cerdo
Clostridioides difficile
Pseudomembranous colitis
Colitis pseudomembranosa
topic Gnotobiotic Animals
Swine
Animales Notobióticos
Cerdo
Clostridioides difficile
Pseudomembranous colitis
Colitis pseudomembranosa
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.
Instituto de Virología
Fil: Nyblade, Charlotte. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Parreño, Gladys Viviana. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhou, Peng. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Hensley, Casey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Oakes, Vanessa. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Mahsoub, Hassan M. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; Estados Unidos
Fil: Kiley, Kelsey. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Maggie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Annie. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhang, Yongrong. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados Unidos
Fil: Feng, Hanping. University of Maryland at Baltimore. Department of Microbial Pathogenesis; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod‑Borne Pathogens; 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 2022-07-19T16:32:40Z
2022-07-19T16:32:40Z
2022-06
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/20.500.12123/12350
https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-022-00496-y
1757-4749
https://doi.org/10.1186/s13099-022-00496-y
url http://hdl.handle.net/20.500.12123/12350
https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-022-00496-y
https://doi.org/10.1186/s13099-022-00496-y
identifier_str_mv 1757-4749
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Gut Pathogens 14 : 22 (Junio 2022)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1846143548586459136
score 12.712165

Publicaciones similares