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However, our\n                    <jats:italic>in vitro<\/jats:italic>\n                    data contradict this assumption and instead document antagonistic interactions between two antibiotics (clarithromycin and amikacin) used to treat\n                    <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n                    infections. Clinically relevant concentrations of clarithromycin induced increased resistance to both amikacin and itself. The induction of resistance was dependent on\n                    <jats:italic>whiB7<\/jats:italic>\n                    , a transcriptional activator of intrinsic antibiotic resistance that is induced by exposure to many different antibiotics. In\n                    <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n                    , the deletion of\n                    <jats:italic>whiB7<\/jats:italic>\n                    (MAB_3508c) resulted in increased sensitivity to a broad range of antibiotics. WhiB7 was required for transcriptional activation of genes that confer resistance to three commonly used anti-\n                    <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n                    drugs: clarithromycin, amikacin, and tigecycline. The\n                    <jats:italic>whiB7<\/jats:italic>\n                    -dependent gene that conferred macrolide resistance was identified as\n                    <jats:italic>erm<\/jats:italic>\n                    (41) (MAB_2297), which encodes a ribosomal methyltransferase. The\n                    <jats:italic>whiB7<\/jats:italic>\n                    -dependent gene contributing to amikacin resistance was\n                    <jats:italic>eis2<\/jats:italic>\n                    (MAB_4532c), which encodes a Gcn5-related\n                    <jats:italic>N<\/jats:italic>\n                    -acetyltransferase (GNAT). Transcription of\n                    <jats:italic>whiB7<\/jats:italic>\n                    and the resistance genes in its regulon was inducible by subinhibitory concentrations of clarithromycin but not by amikacin. Thus, exposure to clarithromycin, or likely any\n                    <jats:italic>whiB7<\/jats:italic>\n                    -inducing antibiotic, may antagonize the activities of amikacin and other drugs. This has important implications for the management of\n                    <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n                    infections, both in cystic fibrosis (CF) and non-CF patients.\n                  <\/jats:p>","DOI":"10.1128\/aac.01353-17","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T20:30:20Z","timestamp":1504643420000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Antagonism between Front-Line Antibiotics Clarithromycin and Amikacin in the Treatment of Mycobacterium abscessus Infections Is Mediated by the\n                    <i>whiB7<\/i>\n                    Gene"],"prefix":"10.1128","volume":"61","author":[{"given":"Mark","family":"Pryjma","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and the Centre for Tuberculosis Research, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1n","family":"Burian","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and the Centre for Tuberculosis Research, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Kuchinski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and the Centre for Tuberculosis Research, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and the Centre for Tuberculosis Research, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8156"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2015.08.023"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2016.04.015"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.11.021"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2016.06.019"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-207360"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/504381"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2014.10.004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.4.716-746.2002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr578"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200905-0704OC"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1684-1182(10)60063-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2014.08.005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw724"},{"key":"e_1_3_3_16_2","first-page":"53","article-title":"Molecular biology of drug resistance in Mycobacterium tuberculosis","volume":"374","author":"Smith T","year":"2013","unstructured":"Smith T WolffKA NguyenL. 2013. 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