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

Ritchie JM, Rui H, Bronson RT, Waldor MK - MBio (2010)

Bottom Line: CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin.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.

View Article: PubMed Central - PubMed

Affiliation: Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Cecal fluid accumulation ratios in infant rabbits inoculated with wild-type or mutant V. cholerae or buffer. Samples were collected 22 h after infection. The ratios were calculated as the weight of accumulated cecal fluid to the weight of drained cecal tissue. Error bars represent the standard deviations of the means. Values that were significantly lower (P < 0.001) than the ratio measured with wild-type (wt) V. cholerae infection are indicated by three asterisks. There were at least seven rabbits in each group.
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f2: Cecal fluid accumulation ratios in infant rabbits inoculated with wild-type or mutant V. cholerae or buffer. Samples were collected 22 h after infection. The ratios were calculated as the weight of accumulated cecal fluid to the weight of drained cecal tissue. Error bars represent the standard deviations of the means. Values that were significantly lower (P < 0.001) than the ratio measured with wild-type (wt) V. cholerae infection are indicated by three asterisks. There were at least seven rabbits in each group.

Mentions: Our attempts to fashion a simple device to directly measure diarrheal fluid loss were unsuccessful. However, measuring the volume of cecal fluid was relatively simple and provided a surrogate measurement for fluid release. We determined a cecal fluid accumulation ratio, defined as the ratio of the weight of fluid drained from the cecum to the weight of cecal tissue, at necropsy for each rabbit. At 22 h postinfection, the ceca of infected rabbits were grossly distended (Fig. 1C) and their fluid accumulation ratios were more than 20 times greater than those from mock-infected rabbits (1.08 ± 0.22 versus 0.05 ± 0.05, respectively) (P < 0.001) (Fig. 2).


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

Ritchie JM, Rui H, Bronson RT, Waldor MK - MBio (2010)

Cecal fluid accumulation ratios in infant rabbits inoculated with wild-type or mutant V. cholerae or buffer. Samples were collected 22 h after infection. The ratios were calculated as the weight of accumulated cecal fluid to the weight of drained cecal tissue. Error bars represent the standard deviations of the means. Values that were significantly lower (P < 0.001) than the ratio measured with wild-type (wt) V. cholerae infection are indicated by three asterisks. There were at least seven rabbits in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2912669&req=5

f2: Cecal fluid accumulation ratios in infant rabbits inoculated with wild-type or mutant V. cholerae or buffer. Samples were collected 22 h after infection. The ratios were calculated as the weight of accumulated cecal fluid to the weight of drained cecal tissue. Error bars represent the standard deviations of the means. Values that were significantly lower (P < 0.001) than the ratio measured with wild-type (wt) V. cholerae infection are indicated by three asterisks. There were at least seven rabbits in each group.
Mentions: Our attempts to fashion a simple device to directly measure diarrheal fluid loss were unsuccessful. However, measuring the volume of cecal fluid was relatively simple and provided a surrogate measurement for fluid release. We determined a cecal fluid accumulation ratio, defined as the ratio of the weight of fluid drained from the cecum to the weight of cecal tissue, at necropsy for each rabbit. At 22 h postinfection, the ceca of infected rabbits were grossly distended (Fig. 1C) and their fluid accumulation ratios were more than 20 times greater than those from mock-infected rabbits (1.08 ± 0.22 versus 0.05 ± 0.05, respectively) (P < 0.001) (Fig. 2).

Bottom Line: CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin.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.

View Article: PubMed Central - PubMed

Affiliation: Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

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.

No MeSH data available.


Related in: MedlinePlus