{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:47:23Z","timestamp":1791352043662,"version":"4.3.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T00:00:00Z","timestamp":1334620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,5,2]],"date-time":"2012-05-02T00:00:00Z","timestamp":1335916800000},"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":[[2012,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            , the cause of an often fatal infectious diarrhea, remains a large global public health threat. Little is known about the challenges\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            encounters during colonization of the intestines, which genes are important for overcoming these challenges, and how these genes are regulated. In this study, we examined the\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            response to nitric oxide (NO), an antibacterial molecule derived during infection from various sources, including host inducible NO synthase (iNOS). We demonstrate that the regulatory protein NorR regulates the expression of NO detoxification genes\n            <jats:italic>hmpA<\/jats:italic>\n            and\n            <jats:italic>nnrS<\/jats:italic>\n            , and that all three are critical for resisting low levels of NO stress under microaerobic conditions\n            <jats:italic>in vitro<\/jats:italic>\n            . We also show that\n            <jats:italic>prxA<\/jats:italic>\n            , a gene previously thought to be important for NO detoxification, plays no role in NO resistance under microaerobic conditions and is upregulated by H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            , not NO. Furthermore, in an adult mouse model of prolonged colonization,\n            <jats:italic>hmpA<\/jats:italic>\n            and\n            <jats:italic>norR<\/jats:italic>\n            were important for the resistance of both iNOS- and non-iNOS-derived stresses. Our data demonstrate that NO detoxification systems play a critical role in the survival of\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            under microaerobic conditions resembling those of an infectious setting and during colonization of the intestines over time periods similar to that of an actual\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            infection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Little is known about what environmental stresses\n            <jats:named-content content-type=\"genus-species\">Vibrio cholerae<\/jats:named-content>\n            , the etiologic agent of cholera, encounters during infection, and even less is known about how\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            senses and counters these stresses. Most prior studies of\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            infection relied on the 24-h infant mouse model, which does not allow the analysis of survival over time periods comparable to that of an actual\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            infection. In this study, we used a sustained mouse colonization model to identify nitric oxide resistance as a function critical for the survival of\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            in the intestines and further identified the genes responsible for sensing and detoxifying this stress.\n          <\/jats:p>","DOI":"10.1128\/mbio.00013-12","type":"journal-article","created":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T04:44:27Z","timestamp":1334724267000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":72,"title":["The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines"],"prefix":"10.1128","volume":"3","author":[{"given":"Andrew M.","family":"Stern","sequence":"first","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona A.","family":"Desland","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengtao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,"},{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.10.150"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01094-07"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0330176"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb800279q"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(99)00019-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2010.04.007"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.13.1.106-115.2006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2004.04484.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70637-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1997.273.5.G1160"},{"key":"e_1_3_2_12_2","first-page":"221","article-title":"Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139","volume":"9","author":"Qadri F","year":"2002","unstructured":"QadriF . 2002. 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Cold Spring Harbor Laboratory, Cold Spring Harbor, NY."}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00013-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00013-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T01:42:38Z","timestamp":1646703758000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00013-12"}},"subtitle":[],"editor":[{"given":"John","family":"Mekalanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,5,2]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,5,2]]}},"alternative-id":["10.1128\/mBio.00013-12"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00013-12","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,2]]},"assertion":[{"value":"2012-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00013-12"}}