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While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium intracellulare<\/jats:named-content>\n                    lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of\n                    <jats:named-content content-type=\"genus-species\">M. intracellulare<\/jats:named-content>\n                    uncovered mutations in a previously uncharacterized locus,\n                    <jats:italic>mmpT5<\/jats:italic>\n                    . Preliminary analysis suggested similarities between\n                    <jats:italic>mmpT5<\/jats:italic>\n                    and the\n                    <jats:italic>mmpR5<\/jats:italic>\n                    locus, which is associated with low-level BDQ resistance in\n                    <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n                    . Both genes encode transcriptional regulators and are adjacent to orthologs of the\n                    <jats:italic>mmpS5-mmpL5<\/jats:italic>\n                    drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous\n                    <jats:italic>mmpT5<\/jats:italic>\n                    mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (\n                    <jats:italic>atpE<\/jats:italic>\n                    ), the primary target of BDQ. Susceptibility testing indicated that\n                    <jats:italic>mmpT5<\/jats:italic>\n                    mutations are associated with modest 2- to 8-fold increases in MICs for BDQ and clofazimine, whereas one\n                    <jats:italic>atpE<\/jats:italic>\n                    mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of\n                    <jats:named-content content-type=\"genus-species\">M. intracellulare<\/jats:named-content>\n                    lung disease, but optimization of treatment regimens is required to prevent the emergence of\n                    <jats:italic>mmpT5<\/jats:italic>\n                    variants and microbiological relapse.\n                  <\/jats:p>","DOI":"10.1128\/jcm.02087-16","type":"journal-article","created":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T22:00:43Z","timestamp":1481148043000},"page":"574-584","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["Emergence of\n                    <i>mmpT5<\/i>\n                    Variants during Bedaquiline Treatment of Mycobacterium intracellulare Lung Disease"],"prefix":"10.1128","volume":"55","author":[{"given":"David C.","family":"Alexander","sequence":"first","affiliation":[{"name":"University of Regina, Department of Biology, Regina, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikiran","family":"Vasireddy","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Microbiology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruthi","family":"Vasireddy","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Microbiology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie V.","family":"Philley","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Brown-Elliott","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Microbiology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Perry","sequence":"additional","affiliation":[{"name":"University of Regina, Department of Biology, Regina, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Griffith","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeana L.","family":"Benwill","sequence":"additional","affiliation":[{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Microbiology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"},{"name":"The Mycobacteria\/Nocardia Research Laboratory, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D. 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