{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T01:47:26Z","timestamp":1794275246019,"version":"4.9.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001704","name":"European Society of Clinical Microbiology and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001704","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Association Sport et Collection"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Clin Microbiol Antimicrob"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      is a slow-growing, gram-negative strictly pathogenic bacterium, which colonizes the stomachs of half the global population and is responsible for gastritis, peptic ulcer and even adenocarcinoma, Treatment of choice for eradication is a combination of PPIs and multiple antibiotic therapy. Recently, therapeutic failures began to be attributable to increased antibiotic resistance due to mutations in identified genes\n                      <jats:italic>(rpoB<\/jats:italic>\n                      , 16S rRNA coding gene,\n                      <jats:italic>gyrA<\/jats:italic>\n                      , 23S rRNA coding gene,\n                      <jats:italic>pbp1A<\/jats:italic>\n                      ,\n                      <jats:italic>frxA<\/jats:italic>\n                      ,\n                      <jats:italic>rdxA)<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study aimed to determine, using ultra-deep sequencing, the distribution of mutations in patient s hospitalized or undergoing screening for\n                      <jats:italic>H. pylori<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Gastric biopsies were obtained from two different anatomical regions (antrum\/fundus) in 18 patients\u2019 samples from 1998 to 2021, in four French hospitals. Following automated extraction, DNA of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      was amplified using multiplexed PCR, before sequencing on the Illumina iSeq100 platform.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antral diversification of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      populations is significantly greater than that at the fundic level for\n                      <jats:italic>rpoB<\/jats:italic>\n                      and\n                      <jats:italic>rdxA<\/jats:italic>\n                      . Fundic diversification of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      populations is significantly greater than that at the antral level for the 23S rRNA coding,\n                      <jats:italic>rdxA<\/jats:italic>\n                      and\n                      <jats:italic>rpoB<\/jats:italic>\n                      genes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), with inter-individual variation.Conversely, the 16S rRNA, frxA,\n                      <jats:italic>gyrA<\/jats:italic>\n                      and pbp1A genes exhibited no significant variation (\n                      <jats:italic>p<\/jats:italic>\n                      &gt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This first study using in-house high-throughput sequencing of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      on clinical biopsies from the same patients reinforces the hypothesis that the bacterial population within the same host is heterogeneous. The presence of minority variants justifies the need for at least two biopsies to ensure robust testing of the\n                      <jats:italic>H. pylori<\/jats:italic>\n                      antibiotic susceptibility profile.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12941-025-00840-5","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T18:45:36Z","timestamp":1769107536000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization using ultra-deep sequencing of the intra-host distribution of the mutations associated with H. pylori antibiotic resistance"],"prefix":"10.1186","volume":"25","author":[{"given":"Laura","family":"Chaufour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Herve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birama","family":"Ndiaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Karayan-Tapon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9d\u00e9ric","family":"Briand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Lartigue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Burucoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Pichon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"840_CR1","doi-asserted-by":"publisher","first-page":"104135","DOI":"10.1016\/j.meegid.2019.104135","volume":"78","author":"A Hanafiah","year":"2020","unstructured":"Hanafiah A, Lopes BS. Genetic diversity and virulence characteristics of Helicobacter pylori isolates in different human ethnic groups. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis. 2020;78:104135. https:\/\/doi.org\/10.1016\/j.meegid.2019.104135.","journal-title":"Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis"},{"issue":"31","key":"840_CR2","doi-asserted-by":"publisher","first-page":"3472","DOI":"10.3748\/wjg.v24.i31.3472","volume":"24","author":"NC Quaglia","year":"2018","unstructured":"Quaglia NC, Dambrosio A. Helicobacter pylori: a foodborne pathogen? World J Gastroenterol. 2018;24(31):3472\u201387. https:\/\/doi.org\/10.3748\/wjg.v24.i31.3472.","journal-title":"World J Gastroenterol"},{"key":"840_CR3","unstructured":"HAS. Traitement de l\u2019infection Par Helicobacter Pylori Chez l\u2019adulte. 2017. has.sant\u00e9.fr\/helicobacter_fiche_pertinence_traitement."},{"issue":"3","key":"840_CR4","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1128\/CMR.00054-05","volume":"19","author":"JG Kusters","year":"2006","unstructured":"Kusters JG, van Vliet AHM, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006;19(3):449\u201390. https:\/\/doi.org\/10.1128\/CMR.00054-05.","journal-title":"Clin Microbiol Rev"},{"issue":"2","key":"840_CR5","first-page":"112","volume":"10","author":"S Diaconu","year":"2017","unstructured":"Diaconu S, Predescu A, Moldoveanu A, Pop CS, Fierbin\u021beanu-Braticevici C. Helicobacter pylori infection: old and new. J Med Life. 2017;10(2):112\u20137.","journal-title":"J Med Life"},{"issue":"16","key":"840_CR6","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1056\/NEJM199110173251603","volume":"325","author":"J Parsonnet","year":"1991","unstructured":"Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127\u201331. https:\/\/doi.org\/10.1056\/NEJM199110173251603.","journal-title":"N Engl J Med"},{"key":"840_CR7","doi-asserted-by":"publisher","unstructured":"Malfertheiner P, Megraud F, Rokkas T et al. Management of Helicobacter pylori infection: the Maastricht VI\/Florence consensus report. Gut. Published online August 8, 2022:gutjnl-2022-327745. https:\/\/doi.org\/10.1136\/gutjnl-2022-327745","DOI":"10.1136\/gutjnl-2022-327745"},{"key":"840_CR8","doi-asserted-by":"publisher","first-page":"102304","DOI":"10.1016\/j.coi.2023.102304","volume":"82","author":"S Suerbaum","year":"2023","unstructured":"Suerbaum S, Ailloud F. Genome and population dynamics during chronic infection with Helicobacter pylori. Curr Opin Immunol. 2023;82:102304. https:\/\/doi.org\/10.1016\/j.coi.2023.102304.","journal-title":"Curr Opin Immunol"},{"issue":"3","key":"840_CR9","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1128\/AAC.45.3.727-733.2001","volume":"45","author":"G Wang","year":"2001","unstructured":"Wang G, Wilson TJ, Jiang Q, Taylor DE. Spontaneous mutations that confer antibiotic resistance in Helicobacter pylori. Antimicrob Agents Chemother. 2001;45(3):727\u201333. https:\/\/doi.org\/10.1128\/AAC.45.3.727-733.2001.","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"840_CR10","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1128\/JCM.02352-07","volume":"46","author":"C Burucoa","year":"2008","unstructured":"Burucoa C, Garnier M, Silvain C, Fauch\u00e8re JL. Quadruplex real-time PCR assay using allele-specific Scorpion primers for detection of mutations conferring clarithromycin resistance to Helicobacter pylori. J Clin Microbiol. 2008;46(7):2320\u20136. https:\/\/doi.org\/10.1128\/JCM.02352-07.","journal-title":"J Clin Microbiol"},{"key":"840_CR11","doi-asserted-by":"publisher","unstructured":"Charazac A, Delage R, Pichon M et al. Low-level primary clarithromycin resistance of Helicobacter pylori in Reunion Island. Infect Dis Now. Published online January 2025:105025. https:\/\/doi.org\/10.1016\/j.idnow.2025.105025","DOI":"10.1016\/j.idnow.2025.105025"},{"issue":"4","key":"840_CR12","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1111\/j.1523-5378.2006.00415.x","volume":"11","author":"H Miyachi","year":"2006","unstructured":"Miyachi H, Miki I, Aoyama N, et al. Primary Levofloxacin resistance and gyrA\/B mutations among Helicobacter pylori in Japan. Helicobacter. 2006;11(4):243\u20139. https:\/\/doi.org\/10.1111\/j.1523-5378.2006.00415.x.","journal-title":"Helicobacter"},{"issue":"10","key":"840_CR13","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1093\/jac\/dkae269","volume":"79","author":"V Luzarraga","year":"2024","unstructured":"Luzarraga V, Cremniter J, Plouzeau C, et al. In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates. J Antimicrob Chemother. 2024;79(10):2633\u20139. https:\/\/doi.org\/10.1093\/jac\/dkae269.","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"840_CR14","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1128\/AAC.05243-11","volume":"56","author":"M Garcia","year":"2012","unstructured":"Garcia M, Raymond J, Garnier M, Cremniter J, Burucoa C. Distribution of spontaneous GyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France. Antimicrob Agents Chemother. 2012;56(1):550\u20131. https:\/\/doi.org\/10.1128\/AAC.05243-11.","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"840_CR15","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1046\/j.1365-2958.1998.00806.x","volume":"28","author":"A Goodwin","year":"1998","unstructured":"Goodwin A, Kersulyte D, Sisson G, van Veldhuyzen SJ, Berg DE, Hoffman PS. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol Microbiol. 1998;28(2):383\u201393. https:\/\/doi.org\/10.1046\/j.1365-2958.1998.00806.x.","journal-title":"Mol Microbiol"},{"key":"840_CR16","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1476-0711-9-22","volume":"9","author":"K Ben Mansour","year":"2010","unstructured":"Ben Mansour K, Burucoa C, Zribi M, et al. Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patient s with peptic ulcers and gastritis: a prospective multicentre study. Ann Clin Microbiol Antimicrob. 2010;9:22. https:\/\/doi.org\/10.1186\/1476-0711-9-22.","journal-title":"Ann Clin Microbiol Antimicrob"},{"issue":"1","key":"840_CR17","doi-asserted-by":"publisher","first-page":"e12451","DOI":"10.1111\/hel.12451","volume":"23","author":"C Hays","year":"2018","unstructured":"Hays C, Burucoa C, Lehours P, Tran CT, Leleu A, Raymond J. Molecular characterization of Helicobacter pylori resistance to rifamycins. Helicobacter. 2018;23(1):e12451. https:\/\/doi.org\/10.1111\/hel.12451.","journal-title":"Helicobacter"},{"issue":"9","key":"840_CR18","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1099\/jmm.0.001051","volume":"68","author":"M Contreras","year":"2019","unstructured":"Contreras M, Benejat L, Mujica H, et al. Real-time PCR detection of a 16S rRNA single mutation of Helicobacter pylori isolates associated with reduced susceptibility and resistance to tetracycline in the gastroesophageal mucosa of individual hosts. J Med Microbiol. 2019;68(9):1287\u201391. https:\/\/doi.org\/10.1099\/jmm.0.001051.","journal-title":"J Med Microbiol"},{"issue":"5","key":"840_CR19","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1053\/j.gastro.2018.07.007","volume":"155","author":"A Savoldi","year":"2018","unstructured":"Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and Meta-analysis in world health organization regions. Gastroenterology. 2018;155(5):1372\u2013e138217. https:\/\/doi.org\/10.1053\/j.gastro.2018.07.007.","journal-title":"Gastroenterology"},{"issue":"10","key":"840_CR20","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1136\/gutjnl-2021-324032","volume":"70","author":"F Megraud","year":"2021","unstructured":"Megraud F, Bruyndonckx R, Coenen S, et al. Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community. Gut. 2021;70(10):1815\u201322. https:\/\/doi.org\/10.1136\/gutjnl-2021-324032.","journal-title":"Gut"},{"issue":"15","key":"840_CR21","doi-asserted-by":"publisher","first-page":"4293","DOI":"10.3390\/jcm11154293","volume":"11","author":"M Pichon","year":"2022","unstructured":"Pichon M, Luzarraga V, Burucoa C. Mutations associated to antibiotic-resistant Helicobacter pylori: it is time to validate sequencing observations. J Clin Med. 2022;11(15):4293. https:\/\/doi.org\/10.3390\/jcm11154293.","journal-title":"J Clin Med"},{"issue":"9","key":"840_CR22","doi-asserted-by":"publisher","first-page":"2812","DOI":"10.3390\/jcm9092812","volume":"9","author":"M Pichon","year":"2020","unstructured":"Pichon M, Tran CT, Motillon G, et al. Where to biopsy to detect Helicobacter pylori and how many biopsies are needed to detect antibiotic resistance in a human stomach. J Clin Med. 2020;9(9):2812. https:\/\/doi.org\/10.3390\/jcm9092812.","journal-title":"J Clin Med"},{"issue":"5","key":"840_CR23","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.3390\/jcm11051151","volume":"11","author":"M Pichon","year":"2022","unstructured":"Pichon M, Freche B, Burucoa C. New strategy for the detection and treatment of Helicobacter pylori infections in primary care guided by a Non-Invasive PCR in stool: protocol of the French HepyPrim study. J Clin Med. 2022;11(5):1151. https:\/\/doi.org\/10.3390\/jcm11051151.","journal-title":"J Clin Med"},{"key":"840_CR24","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01787-19","author":"M Pichon","year":"2020","unstructured":"Pichon M, Pichard B, Barrioz T, et al. Diagnostic accuracy of a noninvasive test for detection of Helicobacter pylori and resistance to clarithromycin in stool by the Amplidiag H. pylori\u2009+\u2009ClariR Real-Time PCR assay. J Clin Microbiol. 2020. https:\/\/doi.org\/10.1128\/JCM.01787-19.","journal-title":"J Clin Microbiol"},{"issue":"7","key":"840_CR25","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1093\/clinchem\/hvac023","volume":"68","author":"M Cantu","year":"2022","unstructured":"Cantu M, Morrison MA, Gagan J. Standardized comparison of different DNA sequencing platforms. Clin Chem. 2022;68(7):872\u20136. https:\/\/doi.org\/10.1093\/clinchem\/hvac023.","journal-title":"Clin Chem"}],"container-title":["Annals of Clinical Microbiology and Antimicrobials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12941-025-00840-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12941-025-00840-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12941-025-00840-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T09:06:57Z","timestamp":1769677617000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12941-025-00840-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["840"],"URL":"https:\/\/doi.org\/10.1186\/s12941-025-00840-5","relation":{},"ISSN":["1476-0711"],"issn-type":[{"value":"1476-0711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"assertion":[{"value":"3 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}