{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:34:11Z","timestamp":1790620451967,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,3,18]]},"abstract":"<jats:p>\n                    We have characterized the adaptations of\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    to a rarely captured event in the evolution of its impact on host biology\u2014the transition from chronic atrophic gastritis (ChAG) to gastric adenocarcinoma\u2014and defined the impact of these adaptations on an intriguing but poorly characterized interaction between this bacterium and gastric epithelial stem cells. Bacterial isolates were obtained from a single human host colonized with a single dominant strain before and after his progression from ChAG to gastric adenocarcinoma during a 4-year interval. Draft genome assemblies were generated from two isolates, one ChAG-associated, the other cancer-associated. The cancer-associated strain was less fit in a gnotobiotic transgenic mouse model of human ChAG and better able to establish itself within a mouse gastric epithelial progenitor-derived cell line (mGEP) that supports bacterial attachment. GeneChip-based comparisons of the transcriptomes of mGEPs and a control mouse gastric epithelial cell line revealed that, upon infection, the cancer-associated strain regulates expression of GEP-associated signaling and metabolic pathways, and tumor suppressor genes associated with development of gastric cancer in humans, in a manner distinct from the ChAG-associated isolate. The effects on GEP metabolic pathways, some of which were confirmed in gnotobiotic mice, together with observed changes in the bacterial transcriptome are predicted to support aspects of an endosymbiosis between this microbe and gastric stem cells. These results provide insights about how\n                    <jats:italic>H. pylori<\/jats:italic>\n                    may adapt to and influence stem cell biology and how its intracellular residency could contribute to gastric tumorigenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0800668105","type":"journal-article","created":{"date-parts":[[2008,3,10]],"date-time":"2008-03-10T23:34:04Z","timestamp":1205192044000},"page":"4358-4363","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["<i>Helicobacter pylori<\/i>\n                    evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells"],"prefix":"10.1073","volume":"105","author":[{"given":"Marios","family":"Giannakis","sequence":"first","affiliation":[{"name":"*Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaine L.","family":"Chen","sequence":"additional","affiliation":[{"name":"*Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif M.","family":"Karam","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain 17666, United Arab Emirates;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Engstrand","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden; and"},{"name":"Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I.","family":"Gordon","sequence":"additional","affiliation":[{"name":"*Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,3,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70475-5"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11680"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407657102"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80454-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.01.049"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/35102167"},{"key":"e_1_3_3_7_2","first-page":"1","article-title":"Schistosomes, liver flukes and Helicobacter pylori.","volume":"61","year":"1994","unstructured":", Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum 61, 1\u2013241 (1994).","journal-title":"IARC Monogr Eval Carcinog Risks Hum"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365520410008141"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603784103"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/41483"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/16495"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02623.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192574799"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230380100"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2008.00522.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512118200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504927102"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.04.030"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1755"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2006.12.001"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1288"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3514"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i20.2867"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500031200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5583-4"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6338"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4732-4742.2005"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"962","DOI":"10.4049\/jimmunol.158.2.962","article-title":"T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease.","volume":"158","author":"D'Elios MM","year":"1997","unstructured":"MM D'Elios, et al., T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol 158, 962\u2013967 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.16.3325"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.63.3.675-707.1999"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/35051615"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.19.5137"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404393200"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1454"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.31"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0800668105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T19:40:00Z","timestamp":1684266000000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0800668105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,18]]},"references-count":35,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,3,18]]}},"alternative-id":["10.1073\/pnas.0800668105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0800668105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1103514.575391","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1103514.560505","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1103514.559574","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,18]]},"assertion":[{"value":"2007-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}