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Evidence of Asymptomatic Carriage of Toxigenic Clostridioides difficile in Canines Suggests that Components of the Gut Microbiome Provide Resistance to Disease
Başlık:
Evidence of Asymptomatic Carriage of Toxigenic Clostridioides difficile in Canines Suggests that Components of the Gut Microbiome Provide Resistance to Disease
Yazar:
Stone, Nathan E., author.
ISBN:
9780438015227
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (62 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: David M. Wagner Committee members: Joseph D. Busch; Emily K. Cope.
Özet:
Clostridioides difficile infection (CDI) is an emerging public health threat. Clostridioides difficile is the most common cause of antimicrobial associated diarrhea worldwide and the leading cause of hospital-associated infections in the US, yet the burden of community-acquired infections (CAI) is poorly understood. Characterizing C. difficile isolated from canines is important for understanding the role that canines may play in CAI, and additionally, the interactions between host and pathogen. Several studies have suggested that canines carry toxigenic C. difficile asymptomatically, which may imply that there are mechanisms responsible for resistance to C. difficile in canines that could be exploited to combat human CDI. To assess virulence potential of canine C. difficile we tested whether toxins TcdA and TcdB (hereafter toxins) derived from a canine strain were capable of causing tight junction disruptions to colonic epithelial cells. Additionally, we addressed whether major differences exist between human and canine cells regarding C. difficile toxicity by exposing them to identical toxins. We then examined the canine gut microbiome associated with C. difficile carriage using 16S rRNA gene sequencing and looked for deviations from homeostasis as an indicator of CDI. Finally, we queried 16S rRNA gene sequences for bacterial taxa that may be associated with resistance to C. difficile in canines. Clostridioides difficile isolated from a canine produced toxins that reduced tight junction integrity in canine cells in vitro. However, canine guts were not dysbiotic in the presence of C. difficile. These findings support asymptomatic carriage in canines and, furthermore, suggest features of the gut microbiome and/or a canine-specific immune response that protects against CDI. We identified two biologically relevant bacteria that may aid in C. difficile resistance: 1) Clostridium hiranonis, which synthesizes secondary bile acids that have been shown to provide resistance to CDI in mice, and 2) Sphingobacterium faecium, which produces sphingophospholipids that may be associated with regulating homeostasis in the canine gut. Our findings suggest that canines may be hidden reservoirs for C. difficile and that the mechanisms of CDI resistance in the canine gut could provide insights into targeted therapeutics for human CDI.
Notlar:
School code: 0391
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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