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Back to the future: studying cholera pathogenesis using infant rabbits.

Ritchie, JM, Rui, H, Bronson, RT and Waldor, MK (2010) Back to the future: studying cholera pathogenesis using infant rabbits. MBio, 1 (1). ISSN 2150-7511

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Abstract

Cholera is a severe diarrheal disease, caused by Vibrio cholerae, for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of V. cholerae into 3-day-old rabbits pretreated with cimetidine led to lethal, watery diarrhea in virtually all rabbits. The appearance and chemical composition of the rabbit diarrheal fluid were comparable to those of the "rice-water stool" produced by cholera patients. As in humans, V. cholerae mutants that do not produce cholera toxin (CT) and toxin-coregulated pilus (TCP) did not induce cholera-like disease in rabbits. CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin. Large aggregates of mucin-embedded V. cholerae were observed, both attached to the epithelium and floating within the diarrheal fluid. These findings suggest that CT-dependent mucin secretion significantly influences V. cholerae's association with the host intestine and its exit from the intestinal tract. Our model should facilitate identification and analyses of factors that may govern V. cholerae infection, survival, and transmission, such as mucin. In addition, our results using nontoxigenic V. cholerae suggest that infant rabbits will be useful for study of the reactogenicity of live attenuated-V. cholerae vaccines.

Item Type: Article
Additional Information: Copyright © 2010 Ritchie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Divisions: Faculty of Health and Medical Sciences > Microbial and Cellular Sciences
Depositing User: Symplectic Elements
Date Deposited: 27 Jun 2012 13:42
Last Modified: 23 Sep 2013 19:19
URI: http://epubs.surrey.ac.uk/id/eprint/326415

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