{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:16:46Z","timestamp":1791404206352,"version":"4.3.3"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"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":[[2012,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,\n            <jats:italic>katG<\/jats:italic>\n            mutations were associated with high-level and\n            <jats:italic>inhA<\/jats:italic>\n            promoter mutations with low-level drug resistance. Only\n            <jats:italic>katG<\/jats:italic>\n            (\n            <jats:italic>S315T<\/jats:italic>\n            ) (65.6% of all isoniazid-resistant strains) and\n            <jats:italic>inhA<\/jats:italic>\n            promoter \u221215C\/T (22.7%) were found in molecular clusters.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). Lineage 1 was associated with\n            <jats:italic>inhA<\/jats:italic>\n            promoter \u221215C\/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;\n            <jats:italic>P<\/jats:italic>\n            = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). In conclusion,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            drug resistance mutations were associated with various levels of drug resistance and transmission, and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            drug resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.06460-11","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T04:58:03Z","timestamp":1333429083000},"page":"3047-3053","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":108,"title":["Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"56","author":[{"given":"Lukas","family":"Fenner","sequence":"first","affiliation":[{"name":"Institute of Social and Preventive Medicine, University of Bern, Bern, 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Jaton","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaby E.","family":"Pfyffer","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Luzerner Kantonsspital, Lucerne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Borrell","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Dubuis","sequence":"additional","affiliation":[{"name":"Viollier AG, Allschwil, 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Fehr","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesica Mazza","family":"Stalder","sequence":"additional","affiliation":[{"name":"Division of Pneumology, University Hospital Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Ninet","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, University Hospital of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"B\u00f6ttger","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, National Center for Mycobacteria, University of Zurich, Zurich, 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