{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:52:58Z","timestamp":1790938378329,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2006,7,1]],"date-time":"2006-07-01T00:00:00Z","timestamp":1151712000000},"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":[[2006,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Maintaining\nmetal homeostasis is crucial for the adaptation of\n            <jats:italic>Helicobacter\npylori<\/jats:italic>\n            to the gastric environment. Iron, copper, and nickel\nhomeostasis has recently been demonstrated to be required for the\nestablishment of\n            <jats:italic>H. pylori<\/jats:italic>\n            infection in animal models. Here we\ndemonstrate that the HP0969-0971 gene cluster encoding the Czc-type\nmetal export pump homologs HP0969, HP0970, and the\n            <jats:italic>H.\npylori<\/jats:italic>\n            -specific protein HP0971 forms part of a novel\n            <jats:italic>H.\npylori<\/jats:italic>\n            metal resistance determinant, which is required for gastric\ncolonization and for the modulation of urease activity. Insertional\nmutagenesis of the HP0971, HP0970, or HP0969 genes in\n            <jats:italic>H.\npylori<\/jats:italic>\n            reference strain 26695 resulted in increased sensitivity to\ncadmium, zinc, and nickel (czn), suggesting that the encoded proteins\nconstitute a metal-specific export pump. Accordingly, the genes were\ndesignated\n            <jats:italic>cznC<\/jats:italic>\n            (HP0971),\n            <jats:italic>cznB<\/jats:italic>\n            (HP0970), and\n            <jats:italic>cznA<\/jats:italic>\n            (HP0969). The CznC and CznA proteins play a predominant\nrole in nickel homeostasis, since only the\n            <jats:italic>cznC<\/jats:italic>\n            and\n            <jats:italic>cznA<\/jats:italic>\n            mutants but not the\n            <jats:italic>cznB<\/jats:italic>\n            mutant displayed an 8-\nto 10-fold increase in urease activity. Nickel-specific affinity\nchromatography demonstrated that recombinant versions of CznC and CznB\ncan bind to nickel and that the purified CznB protein interacted with\ncadmium and zinc, since both metals competitively inhibited nickel\nbinding. Finally, single\n            <jats:italic>cznA<\/jats:italic>\n            ,\n            <jats:italic>cznB<\/jats:italic>\n            , and\n            <jats:italic>cznC<\/jats:italic>\n            mutants did not colonize the stomach in a Mongolian\ngerbil-based animal model. This demonstrates that the metal export\nfunctions of\n            <jats:italic>H. pylori cznABC<\/jats:italic>\n            are essential for gastric\ncolonization and underlines the extraordinary importance of metal ion\nhomeostasis for the survival of\n            <jats:italic>H. pylori<\/jats:italic>\n            in the gastric\nenvironment.\n          <\/jats:p>","DOI":"10.1128\/iai.02025-05","type":"journal-article","created":{"date-parts":[[2006,6,21]],"date-time":"2006-06-21T23:10:29Z","timestamp":1150931429000},"page":"3845-3852","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":129,"title":["The Novel\n            <i>Helicobacter pylori<\/i>\n            CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization"],"prefix":"10.1128","volume":"74","author":[{"given":"Frank Nils","family":"Sta\u0308hler","sequence":"first","affiliation":[{"name":"Department\rof Microbiology and Hygiene, Institute of Medical Microbiology and\rHygiene, University Hospital Freiburg, \rHermann-Herder-Str. 11, D-79104 Freiburg,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Odenbreit","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians\rUniversity Munich, Max von Pettenkofer Institute\rfor Hygiene and Medical Microbiology, Munich,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Haas","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians\rUniversity Munich, Max von Pettenkofer Institute\rfor Hygiene and Medical Microbiology, Munich,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wilrich","sequence":"additional","affiliation":[{"name":"Department\rof Microbiology and Hygiene, Institute of Medical Microbiology and\rHygiene, University Hospital Freiburg, \rHermann-Herder-Str. 11, D-79104 Freiburg,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoud H. M. Van","family":"Vliet","sequence":"additional","affiliation":[{"name":"Department of\rGastroenterology and Hepatology, Erasmus MC-University\rMedical Center, Rotterdam, The\rNetherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes G.","family":"Kusters","sequence":"additional","affiliation":[{"name":"Department of\rGastroenterology and Hepatology, Erasmus MC-University\rMedical Center, Rotterdam, The\rNetherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Kist","sequence":"additional","affiliation":[{"name":"Department\rof Microbiology and Hygiene, Institute of Medical Microbiology and\rHygiene, University Hospital Freiburg, \rHermann-Herder-Str. 11, D-79104 Freiburg,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bereswill","sequence":"additional","affiliation":[{"name":"Department\rof Microbiology and Hygiene, Institute of Medical Microbiology and\rHygiene, University Hospital Freiburg, \rHermann-Herder-Str. 11, D-79104 Freiburg,\rGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1996.tb00133.x"},{"key":"e_1_3_2_3_2","unstructured":"Ausubel F. M. R. Brent R. E. Kingston D. D.\nMoore J. G. Seidman J. A. Smith and K.\nStruhl. 1992. Short protocols in molecular biology.\nGreen Publishing Associates\/John Wiley & Sons Inc. New York N.Y."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.21.5948-5953.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-9-2505"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/10.6.673"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7252-7258.2005"},{"key":"e_1_3_2_8_2","first-page":"145","year":"1997","unstructured":"Ge, Z., and D. E. Taylor. 1997. Helicobacter pylori DNA transformation by natural competence and electroporation, p. 145-152. In C. L. Clayton and H. L. Mobley (ed.),Helicobacter pylori protocols . Humana Press, Totowa, N.J.","journal-title":"Helicobacter pylori protocols"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01496.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021531"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.15.4354-4361.2003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01466.x"},{"key":"e_1_3_2_13_2","first-page":"155","volume":"241","year":"1999","unstructured":"McGee, D. J., and H. L. Mobley. 1999. Mechanisms of Helicobacter pylori infection: bacterial factors. Curr. Top. Microbiol. Immunol.241:155-180.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-2508(99)00106-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70056-2"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.10.1.1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02395.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.59.3.451-480.1995"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00048-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.19.7351"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.685-691.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077123"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.5381-5385.2003"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.1.299-302.1994"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.7.3930-3934.2002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1079\/PNS19990020"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70142-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.22.6871-6879.1997"},{"key":"e_1_3_2_29_2","first-page":"404","volume":"8","year":"1990","unstructured":"Sarkar, G., and S. S. Sommer. 1990. The\u201c megaprimer\u201d method of site-directed mutagenesis.BioTechniques8:404-407.","journal-title":"BioTechniques"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.5857"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.10.021"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020542"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/41483"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.4.1477-1482.2005"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.8.4891-4897.2001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.6.2846-2852.2002"},{"key":"e_1_3_2_37_2","first-page":"193","year":"2001","unstructured":"van Vliet, A. H. M., S. Bereswill, and J. G. Kusters. 2001. Ion metabolism and transport, p.193 -206. In H. L. Mobley, G. L. Mendz, and S. L. Hazell (ed.),Helicobacter pylori: physiology and genetics . ASM Press, Washington, D.C.","journal-title":"Helicobacter pylori: physiology and genetics"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01987.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.7.3923-3929.2002"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.23.6700-6708.2002"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.13.4683-4688.2005"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4856-4866.1998"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.4.1245-1250.2006"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.02025-05","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.02025-05","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T06:38:55Z","timestamp":1646462335000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.02025-05"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2006,7]]}},"alternative-id":["10.1128\/IAI.02025-05"],"URL":"https:\/\/doi.org\/10.1128\/iai.02025-05","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7]]},"assertion":[{"value":"2005-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-04-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}