Open AccessOutbreaks of Typhlocolitis Caused by Hypervirulent Group ST1 Clostridioides difficile in Highly Immunocompromised Strains of Mice
Author(s) -
G L Kathleen,
Kvin Lertpiriyapong,
Alessandra Piersigilli,
Irina Dobtsis,
Juliette Ramona Karin Wipf,
Eric R. Littmann,
Ingrid Leiner,
Eric G. Pamer,
Rodolfo J Ricart Arbona,
Neil S Lipman
Publication year - 2020
Publication title -
comparative medicine
Language(s) - English
Resource type - Journals
eISSN - 2769-819X
pISSN - 1532-0820
DOI - 10.30802/aalas-cm-19-000109
Subject(s) - outbreak , diarrhea , feces , microbiology and biotechnology , antibiotics , biology , nod , virology , pathogen , medicine , pathology , in vivo
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- Prkdc scid Il2rg tm1Wjl /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 naïve. 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- Prkdc scid /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.