An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera.
Cholera is a diarrheal disease causing significant morbidity and mortality worldwide. This study aimed to establish an adult mouse model of Vibrio cholerae-induced diarrhea and to characterize its pathophysiology. Ligated ileal loops of adult mice were inoculated for 6, 9, 12 and 18 h with a classic...
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ftdoajarticles:oai:doaj.org/article:da1363bbf6f24e9fa413584f592270e4 2023-05-15T15:14:10+02:00 An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. Sutthipong Sawasvirojwong Potjanee Srimanote Varanuj Chatsudthipong Chatchai Muanprasat 2013-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002293 https://doaj.org/article/da1363bbf6f24e9fa413584f592270e4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3694821?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002293 https://doaj.org/article/da1363bbf6f24e9fa413584f592270e4 PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2293 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002293 2022-12-31T14:11:43Z Cholera is a diarrheal disease causing significant morbidity and mortality worldwide. This study aimed to establish an adult mouse model of Vibrio cholerae-induced diarrhea and to characterize its pathophysiology. Ligated ileal loops of adult mice were inoculated for 6, 9, 12 and 18 h with a classical O1 hypertoxigenic 569B strain of V. cholerae (10(7) CFU/loop). Time-course studies demonstrated that the optimal period for inducing diarrhea was 12 h post-inoculation, when peak intestinal fluid accumulation (loop/weight ratio of ∼0.2 g/cm) occurred with the highest diarrhea success rate (90%). In addition, pathogenic numbers of V. cholerae (∼10(9) CFU/g tissue) were recovered from ileal loops at all time points between 6-18 h post-inoculation with the diarrheagenic amount of cholera toxin being detected in the secreted intestinal fluid at 12 h post-inoculation. Interestingly, repeated intraperitoneal administration of CFTRinh-172 (20 µg every 6 h), an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR), completely abolished the V. cholerae-induced intestinal fluid secretion without affecting V. cholerae growth in vivo. As analyzed by ex vivo measurement of intestinal electrical resistance and in vivo assay of fluorescein thiocyanate (FITC)-dextran trans-intestinal flux, V. cholerae infection had no effect on intestinal paracellular permeability. Measurements of albumin in the diarrheal fluid suggested that vascular leakage did not contribute to the pathogenesis of diarrhea in this model. Furthermore, histological examination of V. cholerae-infected intestinal tissues illustrated edematous submucosa, congestion of small vessels and enhanced mucus secretion from goblet cells. This study established a new adult mouse model of V. cholerae-induced diarrhea, which could be useful for studying the pathogenesis of cholera diarrhea and for evaluating future therapeutics/cholera vaccines. In addition, our study confirmed the major role of CFTR in V. cholerae-induced intestinal fluid secretion. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 6 e2293 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Sutthipong Sawasvirojwong Potjanee Srimanote Varanuj Chatsudthipong Chatchai Muanprasat An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Cholera is a diarrheal disease causing significant morbidity and mortality worldwide. This study aimed to establish an adult mouse model of Vibrio cholerae-induced diarrhea and to characterize its pathophysiology. Ligated ileal loops of adult mice were inoculated for 6, 9, 12 and 18 h with a classical O1 hypertoxigenic 569B strain of V. cholerae (10(7) CFU/loop). Time-course studies demonstrated that the optimal period for inducing diarrhea was 12 h post-inoculation, when peak intestinal fluid accumulation (loop/weight ratio of ∼0.2 g/cm) occurred with the highest diarrhea success rate (90%). In addition, pathogenic numbers of V. cholerae (∼10(9) CFU/g tissue) were recovered from ileal loops at all time points between 6-18 h post-inoculation with the diarrheagenic amount of cholera toxin being detected in the secreted intestinal fluid at 12 h post-inoculation. Interestingly, repeated intraperitoneal administration of CFTRinh-172 (20 µg every 6 h), an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR), completely abolished the V. cholerae-induced intestinal fluid secretion without affecting V. cholerae growth in vivo. As analyzed by ex vivo measurement of intestinal electrical resistance and in vivo assay of fluorescein thiocyanate (FITC)-dextran trans-intestinal flux, V. cholerae infection had no effect on intestinal paracellular permeability. Measurements of albumin in the diarrheal fluid suggested that vascular leakage did not contribute to the pathogenesis of diarrhea in this model. Furthermore, histological examination of V. cholerae-infected intestinal tissues illustrated edematous submucosa, congestion of small vessels and enhanced mucus secretion from goblet cells. This study established a new adult mouse model of V. cholerae-induced diarrhea, which could be useful for studying the pathogenesis of cholera diarrhea and for evaluating future therapeutics/cholera vaccines. In addition, our study confirmed the major role of CFTR in V. cholerae-induced intestinal fluid secretion. |
format |
Article in Journal/Newspaper |
author |
Sutthipong Sawasvirojwong Potjanee Srimanote Varanuj Chatsudthipong Chatchai Muanprasat |
author_facet |
Sutthipong Sawasvirojwong Potjanee Srimanote Varanuj Chatsudthipong Chatchai Muanprasat |
author_sort |
Sutthipong Sawasvirojwong |
title |
An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
title_short |
An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
title_full |
An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
title_fullStr |
An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
title_full_unstemmed |
An Adult Mouse Model of Vibrio cholerae-induced Diarrhea for Studying Pathogenesis and Potential Therapy of Cholera. |
title_sort |
adult mouse model of vibrio cholerae-induced diarrhea for studying pathogenesis and potential therapy of cholera. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002293 https://doaj.org/article/da1363bbf6f24e9fa413584f592270e4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2293 (2013) |
op_relation |
http://europepmc.org/articles/PMC3694821?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002293 https://doaj.org/article/da1363bbf6f24e9fa413584f592270e4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002293 |
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PLoS Neglected Tropical Diseases |
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7 |
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6 |
container_start_page |
e2293 |
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