{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:43:57Z","timestamp":1790297037630,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Most\n            <jats:italic>Helicobacter pylori<\/jats:italic>\n            strains are susceptible to amoxicillin, an important component of combination therapies for\n            <jats:italic>H. pylori<\/jats:italic>\n            eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical\n            <jats:italic>H. pylori<\/jats:italic>\n            isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the \u03b2-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of\n            <jats:italic>Escherichia coli<\/jats:italic>\n            . Replacement of the wild-type HP0597 (\n            <jats:italic>pbp1A<\/jats:italic>\n            ) gene of the amoxicillin-sensitive (Amx\n            <jats:sup>s<\/jats:sup>\n            )\n            <jats:italic>H. pylori<\/jats:italic>\n            strain 1061 by the Hardenberg\n            <jats:italic>pbp1A<\/jats:italic>\n            gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of\n            <jats:italic>pbp1A<\/jats:italic>\n            of the Hardenberg strain, the Amx\n            <jats:sup>s<\/jats:sup>\n            <jats:italic>H. pylori<\/jats:italic>\n            strain 1061, and four amoxicillin-resistant (Amx\n            <jats:sup>r<\/jats:sup>\n            ) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser\n            <jats:sub>414<\/jats:sub>\n            \u2192Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.\n          <\/jats:p>","DOI":"10.1128\/aac.46.7.2229-2233.2002","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:07:23Z","timestamp":1027897643000},"page":"2229-2233","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":86,"title":["Alterations in Penicillin-Binding Protein 1A Confer Resistance to \u03b2-Lactam Antibiotics in\n            <i>Helicobacter pylori<\/i>"],"prefix":"10.1128","volume":"46","author":[{"given":"M. M.","family":"Gerrits","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam"},{"name":"Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Schuijffel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A.","family":"van Zwet","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Regional Public Health Laboratory Groningen\/Drenthe, Hoogeveen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M. J. E.","family":"Vandenbroucke-Grauls","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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