Outbreaks of typhlocolitis caused by hypervirulent group ST1 Clostridioides difficile in highly immunocompromised strains of mice Journal Article
| Authors: | Ma, K. G. L.; Lertpiriyapong, K.; Piersigilli, A.; Dobtsis, I.; Wipf, J. R. K.; Littmann, E. R.; Leiner, I.; Pamer, E. G.; Ricart Arbona, R. J.; Lipman, N. S. |
| Article Title: | Outbreaks of typhlocolitis caused by hypervirulent group ST1 Clostridioides difficile in highly immunocompromised strains of mice |
| Abstract: | Clostridioides difficile is an enteric pathogen that can cause significant clinical disease in both humans and animals. However, clinical disease arises most commonly after treatment with broad-spectrum antibiotics. The organism's ability to cause naturally occurring disease in mice is rare, and little is known about its clinical significance in highly immunocompromised mice. We report on 2 outbreaks of diarrhea associated with C. difficile in mice. In outbreak 1, 182 of approximately 2, 400 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) and related strains of mice became clinically ill after cessation of a 14-d course of 0.12% amoxicillin feed to control an increase in clinical signs associated with Corynebacterium bovis infection. Most mice had been engrafted with human tumors; the remainder were experimentally naìˆve. Affected animals exhibited 1 of 3 clinical syndromes: 1) peracute death; 2) severe diarrhea leading to euthanasia or death; or 3) mild to moderate diarrhea followed by recovery. A given cage could contain both affected and unaffected mice. Outbreak 2 involved a small breeding colony (approximately 50 mice) of NOD. CB17-Prkdcscid/NCrCrl (NOD-scid) mice that had not received antibiotics or experimental manipulations. In both outbreaks, C. difficile was isolated, and toxins A and B were detected in intestinal content or feces. Histopathologic lesions highly suggestive of C. difficile enterotoxemia included fibrinonecrotizing and neutrophilic typhlocolitis with characteristic 'volcano' erosions or pseudomembrane formation. Genomic analysis of 4 isolates (3 from outbreak 1 and 1 from outbreak 2) revealed that these isolates were closely related to a pathogenic human isolate, CD 196. To our knowledge, this report is the first to describe naturally occurring outbreaks of C. difficile-associated typhlocolitis with significant morbidity and mortality in highly immunocompromised strains of mice. |
| Journal Title: | Comparative Medicine |
| Volume: | 70 |
| Issue: | 3 |
| ISSN: | 1532-0820 |
| Publisher: | American Association for Laboratory Animal Science |
| Date Published: | 2020-06-01 |
| Start Page: | 277 |
| End Page: | 290 |
| Language: | English |
| DOI: | 10.30802/aalas-cm-19-000109 |
| PUBMED: | 32404234 |
| PROVIDER: | scopus |
| PMCID: | PMC7287380 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2020 -- Source: Scopus |
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