{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:56:17Z","timestamp":1789923377178,"version":"4.0.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000},"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":[[2003,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Four clinical\n            <jats:italic>Helicobacter pylori<\/jats:italic>\n            isolates with high-level resistance to \u03b2-lactams exhibited low- to moderate-level resistance to the structurally and functionally unrelated antibiotics ciprofloxacin, chloramphenicol, metronidazole, rifampin, and tetracycline. This pattern of multidrug resistance was transferable to susceptible\n            <jats:italic>H. pylori<\/jats:italic>\n            by natural transformation using naked genomic DNA from a clinical multidrug-resistant isolate. Acquisition of the multidrug resistance was also associated with a change in the genotype of the transformed multidrug-resistant\n            <jats:italic>H. pylori<\/jats:italic>\n            . DNA sequence analyses of the gene encoding penicillin binding protein 1A (PBP 1A) showed 36 nucleotide substitutions resulting in 10 amino acid changes in the C-terminal portion (the putative penicillin binding domain). Acquisition of \u03b2-lactam resistance was consistently associated with transfer of a mosaic block containing the C-terminal portion of PBP 1A. No changes of genes\n            <jats:italic>gyrA<\/jats:italic>\n            ,\n            <jats:italic>rpoB<\/jats:italic>\n            ,\n            <jats:italic>rrn16S<\/jats:italic>\n            ,\n            <jats:italic>rdxA<\/jats:italic>\n            , and\n            <jats:italic>frxA,<\/jats:italic>\n            and nine other genes (\n            <jats:italic>ftsI<\/jats:italic>\n            ,\n            <jats:italic>hcpA<\/jats:italic>\n            ,\n            <jats:italic>llm<\/jats:italic>\n            ,\n            <jats:italic>lytB<\/jats:italic>\n            ,\n            <jats:italic>mreB<\/jats:italic>\n            ,\n            <jats:italic>mreC<\/jats:italic>\n            ,\n            <jats:italic>pbp2<\/jats:italic>\n            ,\n            <jats:italic>pbp4<\/jats:italic>\n            , and\n            <jats:italic>rodA1<\/jats:italic>\n            ) encoding putative PBPs or involved in cell wall synthesis were found among the transformed resistant\n            <jats:italic>H. pylori<\/jats:italic>\n            . Antibiotic accumulations of chloramphenicol, penicillin, and tetracycline were all significantly decreased in the natural and transformed resistant\n            <jats:italic>H. pylori<\/jats:italic>\n            compared to what was seen with susceptible\n            <jats:italic>H. pylori.<\/jats:italic>\n            Natural transformation also resulted in the outer membrane protein profiles of the transformed resistant\n            <jats:italic>H. pylori<\/jats:italic>\n            becoming similar to that of the clinical resistant\n            <jats:italic>H. pylori<\/jats:italic>\n            isolates. Overall, these results demonstrate that high-level \u03b2-lactam resistance associated with acquired multidrug resistance in clinical\n            <jats:italic>H. pylori<\/jats:italic>\n            is mediated by combination strategies including alterations of PBP 1A and decreased membrane permeability.\n          <\/jats:p>","DOI":"10.1128\/aac.47.7.2169-2178.2003","type":"journal-article","created":{"date-parts":[[2003,6,23]],"date-time":"2003-06-23T19:17:06Z","timestamp":1056395826000},"page":"2169-2178","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["High-Level \u03b2-Lactam Resistance Associated with Acquired Multidrug Resistance in\n            <i>Helicobacter pylori<\/i>"],"prefix":"10.1128","volume":"47","author":[{"given":"Dong H.","family":"Kwon","sequence":"first","affiliation":[{"name":"Veterans Affairs Medical Center and Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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