{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:24:22Z","timestamp":1772825062543,"version":"3.50.1"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI073785"],"award-info":[{"award-number":["R01 AI073785"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007362"],"award-info":[{"award-number":["T32 AI007362"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI118689"],"award-info":[{"award-number":["T32 AI118689"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Genes carried on the type 3 secretion system (T3SS) pathogenicity island of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Vibrio cholerae<\/jats:named-content>\n            non-O1\/non-O139 serogroup strain AM-19226 must be precisely regulated in order for bacteria to cause disease. Previously reported results showed that both T3SS function and the presence of bile are required to cause Caco2-BBE cell cytotoxicity during coculture with strain AM-19226. We therefore investigated additional parameters affecting\n            <jats:italic>in vitro<\/jats:italic>\n            cell death, including bacterial load and the role of three transmembrane transcriptional regulatory proteins, VttR\n            <jats:sub>A<\/jats:sub>\n            , VttR\n            <jats:sub>B<\/jats:sub>\n            , and ToxR. VttR\n            <jats:sub>A<\/jats:sub>\n            and VttR\n            <jats:sub>B<\/jats:sub>\n            are encoded on the horizontally acquired T3SS genomic island, whereas ToxR is encoded on the ancestral chromosome. While strains carrying deletions in any one of the three transcriptional regulatory genes are unable to cause eukaryotic cell death, the results of complementation studies point to a hierarchy of regulatory control that converges on\n            <jats:italic>vttR<\/jats:italic>\n            <jats:sub>B<\/jats:sub>\n            expression. The data suggest both that ToxR and VttR\n            <jats:sub>A<\/jats:sub>\n            act upstream of VttR\n            <jats:sub>B<\/jats:sub>\n            and that modifying the level of either\n            <jats:italic>vttR<\/jats:italic>\n            <jats:sub>A<\/jats:sub>\n            or\n            <jats:italic>vttR<\/jats:italic>\n            <jats:sub>B<\/jats:sub>\n            expression can strongly influence T3SS gene expression. We therefore propose a model whereby T3SS activity and, hence,\n            <jats:italic>in vitro<\/jats:italic>\n            cytotoxicity are ultimately regulated by\n            <jats:italic>vttR<\/jats:italic>\n            <jats:sub>B<\/jats:sub>\n            expression.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            In contrast to O1 and O139 serogroup\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">V. cholerae<\/jats:named-content>\n            strains that cause cholera using two main virulence factors (toxin-coregulated pilus [TCP] and cholera toxin [CT]), O39 serogroup strain AM-19226 uses a type 3 secretion system as its principal virulence mechanism. Although the regulatory network governing TCP and CT expression is well understood, the factors influencing T3SS-associated virulence are not. Using an\n            <jats:italic>in vitro<\/jats:italic>\n            mammalian cell model to investigate the role of three ToxR-like transmembrane transcriptional activators in causing T3SS-dependent cytotoxicity, we found that expression levels and a hierarchical organization were important for promoting T3SS gene expression. Furthermore, our results suggest that horizontally acquired, ToxR-like proteins act in concert with the ancestral ToxR protein to orchestrate T3SS-mediated pathogenicity.\n          <\/jats:p>","DOI":"10.1128\/jb.00130-16","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T02:18:48Z","timestamp":1459217928000},"page":"1675-1682","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Regulation by ToxR-Like Proteins Converges on\n            <i>vttR<\/i>\n            <sub>B<\/sub>\n            Expression To Control Type 3 Secretion System-Dependent Caco2-BBE Cytotoxicity in Vibrio cholerae"],"prefix":"10.1128","volume":"198","author":[{"given":"Kelly A.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline K.","family":"Sofia","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob W. A.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher H.","family":"Seward","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Dziejman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01094-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.3.335"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.4.1080-1087.1996"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.21.6974-6980.1992"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02111.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.11.3228-3238.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00193-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15328-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60436-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.31.5.1315-1317.1993"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.10.2715-2722.1995"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268899002137"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1903.121156"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-52"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-94-5-656"},{"key":"e_1_3_2_18_2","first-page":"474","article-title":"Clinical characteristics of non-O1\/non-O139 Vibrio cholerae isolates and polymerase chain reaction analysis of their virulence factors","volume":"40","author":"Lee YL","year":"2007","unstructured":"Lee YL, Hung PP, Tsai CA, Lin YH, Liu CE, Shi ZY. 2007. Clinical characteristics of non-O1\/non-O139 Vibrio cholerae isolates and polymerase chain reaction analysis of their virulence factors. J Microbiol Immunol Infect 40:474\u2013480.","journal-title":"J Microbiol Immunol Infect"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.3.756-763.1998"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042667999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01317-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02026-08"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409918102"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308485100"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00106-11"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.03.005"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01194-10"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.08.014"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.09.015"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00289-10"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141038"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01073-09"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00832-12"},{"key":"e_1_3_2_34_2","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook J","year":"1989","unstructured":"Sambrook J, Fritsch EF, Maniatis T. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.","edition":"2"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.02151-12"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.14.4121-4130.1995"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008678"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12408"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.9898"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.11.3471"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.59.12.4310-4317.1991"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00130-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00130-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:40:29Z","timestamp":1627580429000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.00130-16"}},"subtitle":[],"editor":[{"given":"V. J.","family":"DiRita","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1128\/JB.00130-16"],"URL":"https:\/\/doi.org\/10.1128\/jb.00130-16","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"2016-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}