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Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease
Resumen
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
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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.
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Autor
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;
Fuente
Gut Pathogens 14 : 22 (Junio 2022)
Fecha
2022-06
Editorial
BioMed Central
ISSN
1757-4749
Formato
pdf
Tipo de documento
artículo
Palabras Claves
Derechos de acceso
Abierto
Excepto donde se diga explicitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)