{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:52:09Z","timestamp":1791017529437,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T00:00:00Z","timestamp":1473206400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100012483","name":"University of Georgia Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012483","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,9,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A known virulence factor of\n            <jats:named-content content-type=\"genus-species\">Helicobacter pylori<\/jats:named-content>\n            that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128. A \u0394\n            <jats:italic>hyd<\/jats:italic>\n            mutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-\n            <jats:italic>n<\/jats:italic>\n            -heptyl-4-hydroxyquinoline-\n            <jats:italic>N<\/jats:italic>\n            -oxide (HQNO) was used to specifically inhibit the H\n            <jats:sub>2<\/jats:sub>\n            -utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H\n            <jats:sub>2<\/jats:sub>\n            -generated transmembrane potential is a contributor to toxin translocation. The \u0394\n            <jats:italic>hyd<\/jats:italic>\n            strain showed a decreased frequency of DNA transformation, suggesting that\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            hydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the \u0394\n            <jats:italic>hyd<\/jats:italic>\n            strain to induce inflammation was significantly attenuated (at 12\u00a0weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the \u0394\n            <jats:italic>hyd<\/jats:italic>\n            strain. By examining the hydrogenase activities from well-defined clinical\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            isolates, we observed that strains isolated from cancer patients (\n            <jats:italic>n<\/jats:italic>\n            = 6) have a significantly higher hydrogenase (H\n            <jats:sub>2<\/jats:sub>\n            \/O\n            <jats:sub>2<\/jats:sub>\n            ) activity than the strains isolated from gastritis patients (\n            <jats:italic>n<\/jats:italic>\n            = 6), further supporting an association between\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            hydrogenase activity and gastric carcinogenesis in humans.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Hydrogen-utilizing hydrogenases are known to be important for some respiratory pathogens to colonize hosts. Here a gastric cancer connection is made via a pathogen\u2019s (\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            ) use of molecular hydrogen, a host microbiome-produced gas. Delivery of the known carcinogenic factor CagA into host cells is augmented by the H\n            <jats:sub>2<\/jats:sub>\n            -utilizing respiratory chain of the bacterium. The role of hydrogenase in carcinogenesis is demonstrated in an animal model, whereby inflammation markers and cancer development were attenuated in the hydrogenase-null strain. Hydrogenase activity comparisons of clinical strains of the pathogen also support a connection between hydrogen metabolism and gastric cancer risk. While molecular hydrogen use is acknowledged to be an alternative high-energy substrate for some pathogens, this work extends the roles of H\n            <jats:sub>2<\/jats:sub>\n            oxidation to include transport of a carcinogenic toxin. The work provides a new avenue for exploratory treatment of some cancers via microflora alterations.\n          <\/jats:p>","DOI":"10.1128\/mbio.01022-16","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:48:54Z","timestamp":1471394934000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation"],"prefix":"10.1128","volume":"7","author":[{"given":"Ge","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Romero-Gallo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane L.","family":"Benoit","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Blanca","family":"Piazuelo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo L.","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Hospital de Occidente, Ministry of Health, Santa Rosa de Copan, Honduras"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Richard M.","family":"Peek","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"},{"name":"Departments of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.10.4.720"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00054-05"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa001999"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2013.01.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.03031.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08035.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.02.008"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5457.1497"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067147"},{"key":"e_1_3_3_11_2","first-page":"2111","article-title":"Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach","volume":"55","author":"Blaser MJ","year":"1995","unstructured":"Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A. 1995. 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