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Although this resistance is mainly associated with mutations in the\n            <jats:italic>rdxA<\/jats:italic>\n            and\n            <jats:italic>frxA<\/jats:italic>\n            genes, the question of whether metronidazole resistance is caused by the inactivation of\n            <jats:italic>frxA<\/jats:italic>\n            alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. pylori<\/jats:named-content>\n            strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. pylori<\/jats:named-content>\n            strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in\n            <jats:italic>frxA<\/jats:italic>\n            (\n            <jats:italic>hp0642<\/jats:italic>\n            ),\n            <jats:italic>rdxA<\/jats:italic>\n            (\n            <jats:italic>hp0954<\/jats:italic>\n            ), and\n            <jats:italic>rpsU<\/jats:italic>\n            (\n            <jats:italic>hp0562<\/jats:italic>\n            ) were confirmed by the Sanger method. The mutated sequence in\n            <jats:italic>rdxA<\/jats:italic>\n            was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in\n            <jats:italic>rdxA<\/jats:italic>\n            showed a low MIC (16 mg\/liter), while those containing mutations in both\n            <jats:italic>rdxA<\/jats:italic>\n            and\n            <jats:italic>frxA<\/jats:italic>\n            showed a higher MIC (48 mg\/liter). No transformants containing a single mutation in\n            <jats:italic>frxA<\/jats:italic>\n            or\n            <jats:italic>rpsU<\/jats:italic>\n            were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in\n            <jats:italic>rdxA<\/jats:italic>\n            are mainly associated with metronidazole resistance, and mutations in\n            <jats:italic>frxA<\/jats:italic>\n            are able to enhance\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. pylori<\/jats:named-content>\n            resistance only in the presence of\n            <jats:italic>rdxA<\/jats:italic>\n            mutations. Moreover, mutations in\n            <jats:italic>rpsU<\/jats:italic>\n            may play a role in metronidazole resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.04852-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T06:04:54Z","timestamp":1422943494000},"page":"2343-2348","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Search for Novel Candidate Mutations for Metronidazole Resistance in Helicobacter pylori Using Next-Generation Sequencing"],"prefix":"10.1128","volume":"59","author":[{"given":"Tran Thanh","family":"Binh","sequence":"first","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan"},{"name":"Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Thi Huyen","family":"Trang","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyeon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Biology Department, Long Island University, Brooklyn, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan"},{"name":"Department of Medicine-Gastroenterology, Baylor College of Medicine, and Michael E. 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