Document Detail


Back to the future: studying cholera pathogenesis using infant rabbits.
MedLine Citation:
PMID:  20689747     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jennifer M Ritchie; Haopeng Rui; Roderick T Bronson; Matthew K Waldor
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Publication Detail:
Type:  Journal Article     Date:  2010-05-18
Journal Detail:
Title:  mBio     Volume:  1     ISSN:  2150-7511     ISO Abbreviation:  MBio     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-08-06     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101519231     Medline TA:  MBio     Country:  United States    
Other Details:
Languages:  eng     Pagination:  -     Citation Subset:  -    
Affiliation:
Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R37 AI042347-16/AI/NIAID NIH HHS
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