{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:21:43Z","timestamp":1792707703483,"version":"4.5.0"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host.\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            employs the second messenger molecule 3\u2032,5\u2032-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            , and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            . We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.\n          <\/jats:p>","DOI":"10.1128\/iai.01664-14","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T03:34:01Z","timestamp":1399347241000},"page":"3002-3014","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":87,"title":["Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae"],"prefix":"10.1128","volume":"82","author":[{"given":"Benjamin J.","family":"Koestler","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00248-003-2007-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.45.1.275-283.1983"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.56.6.1977-1980.1990"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04155.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04206.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.018"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511090103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.21.6223-6229.1995"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03401.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5873-5882.2005"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2004.00633.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01079-06"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.14.4774-4781.2005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600345103"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10814.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2011.04.014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07259.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2013.04.026"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi101448t"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912839107"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113790108"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi901409g"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.03.015"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.21.7434-7443.2005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/B978-1-4160-6189-2.00064-0","volume-title":"Sleisenger and Fordtran's gastrointestinal and liver disease (9th)","author":"Dawson PA","year":"2010","unstructured":"DawsonPA. 2010. Bile secretion and the enterohepatic circulation, p 1075\u20131088. In FeldmanMFriedmanLSBrandtLJ (ed), Sleisenger and Fordtran's gastrointestinal and liver disease (9th), vol 1. WB Saunders, Philadelphia, PA."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0001-8686(85)80002-6"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsre.2004.09.003"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002849900420"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00424a015"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00381a002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.3.1491-1497.2000"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00657.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.7.4681-4685.2001"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01620-07"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04846.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.7.2853-2856.1996"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(94)35157-0"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01756-07"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00829-2"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052694299"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2000.01704.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.14.7.513"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.22.3.405-408.1985"},{"key":"e_1_3_3_45_2","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook J","year":"1989","unstructured":"SambrookJFritschEFManiatisT. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.","edition":"2"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115663109"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05167-11"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120096"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000068"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07470.x"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90358-6"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01307-08"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01337-07"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.22.2647"},{"key":"e_1_3_3_56_2","first-page":"685","article-title":"TOPPRED-II\u2014an improved software for membrane-protein structure predictions","volume":"10","author":"Claros MG","year":"1994","unstructured":"ClarosMGVonheijneG. 1994. TOPPRED-II\u2014an improved software for membrane-protein structure predictions. Comput. Appl. Biosci. 10:685\u2013686.","journal-title":"Comput. Appl. Biosci."},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp493"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.231"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00564-08"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002719"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409559102"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-382026-6.00048-8"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.1994.tb00319.x"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00409-09"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.170219997"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.5.1508-1514.1999"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.3.1131-1134.1997"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01435-06"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218039110"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01596-13"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01240-08"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-14-22"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-S1-S11"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00889-12"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2628026100"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.68.12.6005-6012.2002"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00295-8"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00048-10"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(87)90619-6"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.6763-6769.2000"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(03)00032-8"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01664-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01664-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T12:45:25Z","timestamp":1646484325000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01664-14"}},"subtitle":[],"editor":[{"given":"A.","family":"Camilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":80,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1128\/IAI.01664-14"],"URL":"https:\/\/doi.org\/10.1128\/iai.01664-14","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7]]},"assertion":[{"value":"2014-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}