{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T18:02:50Z","timestamp":1771351370810,"version":"3.50.1"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"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":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Dysregulated immune responses to commensal intestinal bacteria, including\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            , contribute to the development of inflammatory bowel diseases (IBDs) and experimental colitis. Reciprocally,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            responds to chronic intestinal inflammation by upregulating expression of stress response genes, including\n            <jats:italic>gadA<\/jats:italic>\n            and\n            <jats:italic>gadB<\/jats:italic>\n            . GadAB encode glutamate decarboxylase and protect\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            from the toxic effects of low pH and fermentation acids, factors present in the intestinal lumen in patients with active IBDs. We hypothesized that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            upregulates\n            <jats:italic>gadAB<\/jats:italic>\n            during inflammation to enhance its survival and virulence. Using real-time PCR, we determined\n            <jats:italic>gadAB<\/jats:italic>\n            expression in luminal\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            from ex-germfree wild-type (WT) and interleukin-10 (IL-10) knockout (KO) (IL-10\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice selectively colonized with a commensal\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            isolate (NC101) that causes colitis in KO mice in isolation or in combination with 7 other commensal intestinal bacterial strains.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            survival and host inflammatory responses were measured in WT and KO mice colonized with NC101 or a mutant lacking the\n            <jats:italic>gadAB<\/jats:italic>\n            genes (NC101\u0394\n            <jats:italic>gadAB<\/jats:italic>\n            ). The susceptibility of NC101 and NC101\u0394\n            <jats:italic>gadAB<\/jats:italic>\n            to killing by host antimicrobial peptides and their translocation across intestinal epithelial cells were evaluated using bacterial killing assays and transwell experiments, respectively. We show that expression of\n            <jats:italic>gadAB<\/jats:italic>\n            in luminal\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            increases proportionately with intestinal inflammation in KO mice and enhances the susceptibility of NC101 to killing by the host antimicrobial peptide cryptdin-4 but decreases bacterial transmigration across intestinal epithelial cells, colonic inflammation, and mucosal immune responses. Chronic intestinal inflammation upregulates acid tolerance pathways in commensal\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            isolates, which, contrary to our original hypothesis, limits their survival and colitogenic potential. Further investigation of microbial adaptation to immune-mediated inflammation may provide novel insights into the pathogenesis and treatment of IBDs.\n          <\/jats:p>","DOI":"10.1128\/iai.00355-13","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T02:44:54Z","timestamp":1374547494000},"page":"3662-3671","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Inflammation-Induced Acid Tolerance Genes\n            <i>gadAB<\/i>\n            in Luminal Commensal Escherichia coli Attenuate Experimental Colitis"],"prefix":"10.1128","volume":"81","author":[{"given":"Sandrine","family":"Tchaptchet","sequence":"first","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Jia","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Goeser","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexi","family":"Schoenborn","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay S.","family":"Gulati","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Balfour","family":"Sartor","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan J.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.31.100177.000543"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03668.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000112"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.061"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.11.059"},{"key":"e_1_3_3_7_2","first-page":"19","volume-title":"The inflammatory bowel disease yearbook","author":"Hansen JJ","year":"2007","unstructured":"HansenJJSartorRB. 2007. Insights from animal models, p 19\u201355. In The inflammatory bowel disease yearbook, vol 4. Remedica Publishing Ltd, London, United Kingdom."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.11.5224-5231.1998"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.009"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80069-Q"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118878"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01124-12"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5310.250"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09415"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.064"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.11.3525-3535.1999"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01430.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01297074"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-199402000-00007"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(88)80078-7"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01306-06"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.117713"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.72.4.2556-2563.2006"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.1.210"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114198"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135245"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.04.053"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2007.00800.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2010.05.002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/007575-0"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80312-8"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(92)91111-G"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01246-08"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00101.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.5.2518-2524.2000"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00050.2009"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.10.3190-3201.2003"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00355-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00355-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T12:15:59Z","timestamp":1646482559000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00355-13"}},"subtitle":[],"editor":[{"given":"A. J.","family":"B\u00e4umler","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,10]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1128\/IAI.00355-13"],"URL":"https:\/\/doi.org\/10.1128\/iai.00355-13","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10]]},"assertion":[{"value":"2013-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}