{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:57:47Z","timestamp":1792706267690,"version":"4.5.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,5,18]],"date-time":"2010-05-18T00:00:00Z","timestamp":1274140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2010,5,18]],"date-time":"2010-05-18T00:00:00Z","timestamp":1274140800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2010,5,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cholera is a severe diarrheal disease, caused by\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            , for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            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 \u201crice-water stool\u201d produced by cholera patients. As in humans,\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            mutants that do\u00a0not produce cholera toxin (CT) and toxin-coregulated pilus (TCP) did\u00a0not induce cholera-like disease in rabbits. CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            was predominantly found in close association with mucin. Large aggregates of mucin-embedded\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            were observed, both attached to the epithelium and floating within the diarrheal fluid. These findings suggest that CT-dependent mucin secretion significantly influences\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            \u2019s association with the host intestine and its exit from the intestinal tract. Our model should facilitate identification and analyses of factors that may govern\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            infection, survival, and transmission, such as mucin. In addition, our results using nontoxigenic\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            suggest that infant rabbits will be useful for study of the reactogenicity of live attenuated-\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            vaccines.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Cholera remains a significant threat to populations in developing nations. Currently, there is no reproducible, nonsurgical animal model of cholera, the secretory diarrheal disease caused by\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            . We found that oral infection of infant rabbits with\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            led to lethal, watery diarrhea in most rabbits. Using this disease model, we discovered a new role for cholera toxin (CT) during infection. This toxin not only caused secretory diarrhea but also profoundly influenced how\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            associates with the intestine and how the pathogen exits from the host. Rabbits inoculated with\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            that does\u00a0not produce CT developed mild diarrhea, suggesting that this model may prove useful for generating improved live attenuated-\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            vaccine candidates. Overall, our findings suggest that the infant rabbit model will enable pursuit of several new avenues for research on cholera pathogenesis, as well as serve as a vehicle for testing new therapeutics.\n          <\/jats:p>","DOI":"10.1128\/mbio.00047-10","type":"journal-article","created":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T15:57:44Z","timestamp":1267459064000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":101,"title":["Back to the Future: Studying Cholera Pathogenesis Using Infant Rabbits"],"prefix":"10.1128","volume":"1","author":[{"given":"Jennifer M.","family":"Ritchie","sequence":"first","affiliation":[{"name":"Channing Laboratory, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haopeng","family":"Rui","sequence":"additional","affiliation":[{"name":"Channing Laboratory, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Channing Laboratory, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.5.1409"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp068144"},{"key":"e_1_3_2_4_2","first-page":"309","article-title":"Cholera: global surveillance summary, 2008","volume":"84","author":"WHO","year":"2009","unstructured":"WHO . 2009. 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