{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:02:53Z","timestamp":1791165773521,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":["Infect Immun"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Diverse environmental stimuli and a complex network of regulatory factors are known to modulate expression of\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            's principal virulence factors. However, there is relatively little known about how metabolic factors impinge upon the pathogen's well-characterized cascade of transcription factors that induce expression of cholera toxin and the toxin-coregulated pilus (TCP). Here, we used a transposon insertion site (TIS) sequencing-based strategy to identify new factors required for expression of\n            <jats:italic>tcpA<\/jats:italic>\n            , which encodes the major subunit of TCP, the organism's chief intestinal colonization factor. Besides identifying most of the genes known to modulate\n            <jats:italic>tcpA<\/jats:italic>\n            expression, the screen yielded\n            <jats:italic>ptsI<\/jats:italic>\n            and\n            <jats:italic>ptsH<\/jats:italic>\n            , which encode the enzyme I (EI) and Hpr components of the\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            phosphoenolpyruvate phosphotransferase system (PTS). In addition to reduced expression of TcpA, strains lacking EI, Hpr, or the associated EIIA\n            <jats:sup>Glc<\/jats:sup>\n            protein produced less cholera toxin (CT) and had a diminished capacity to colonize the infant mouse intestine. The PTS modulates virulence gene expression by regulating expression of\n            <jats:italic>tcpPH<\/jats:italic>\n            and\n            <jats:italic>aphAB<\/jats:italic>\n            , which themselves control expression of\n            <jats:italic>toxT<\/jats:italic>\n            , the central activator of virulence gene expression. One mechanism by which PTS promotes virulence gene expression appears to be by modulating the amounts of intracellular cyclic AMP (cAMP). Our findings reveal that the\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            PTS is an additional modulator of the ToxT regulon and demonstrate the potency of loss-of-function TIS sequencing screens for defining regulatory networks.\n          <\/jats:p>","DOI":"10.1128\/iai.00411-15","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T19:10:03Z","timestamp":1433963403000},"page":"3381-3395","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["A Genome-Wide Screen Reveals that the Vibrio cholerae Phosphoenolpyruvate Phosphotransferase System Modulates Virulence Gene Expression"],"prefix":"10.1128","volume":"83","author":[{"given":"Qiyao","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, China"},{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves A.","family":"Millet","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumpei","family":"Sasabe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60436-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.2833"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07244.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01094-07"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5403"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.21.6974-6980.1992"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01215.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00193-10"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05693.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1986.tb03037.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00182-10"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81551-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.07.007"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00409-09"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014640108"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218039110"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915021107"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411570111"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900595106"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.1.265"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02518.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.064865-0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00001-14"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00024-06"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.59.12.4310-4317.1991"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004433"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt654"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004782"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002946"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.045"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.10.944"},{"key":"e_1_3_3_34_2","first-page":"433","article-title":"Selection of reference genes for gene expression analysis in Vibrio cholerae","volume":"30","author":"Zhang C","year":"2014","unstructured":"Zhang C, Pang B, Jiang X, Kan B. 2014. Selection of reference genes for gene expression analysis in Vibrio cholerae. Chin J Zoonoses 30:433\u2013438.","journal-title":"Chin J Zoonoses"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00168-10"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3733-3739.1999"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.14.4250-4256.1999"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7991"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02857.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00726.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00012-14"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803281105"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00213-10"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00228-12"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01356-09"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01410-07"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001102"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004405"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90430-2"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.163.2.580-585.1985"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.04.022"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1932"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12250"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00972-06"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/006668-0"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12557"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915164107"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00411-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00411-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:09:08Z","timestamp":1646474948000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00411-15"}},"subtitle":[],"editor":[{"given":"B. A.","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":56,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1128\/IAI.00411-15"],"URL":"https:\/\/doi.org\/10.1128\/iai.00411-15","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"2015-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}