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We show that the balanced activities and coordinated expression of two genes,\n                    <jats:italic>pikR1<\/jats:italic>\n                    and\n                    <jats:italic>pikR2<\/jats:italic>\n                    , provide efficient protection to\n                    <jats:italic>Streptomyces venezuelae<\/jats:italic>\n                    , a bacterial producer of natural ketolides. Expression of the more potent gene,\n                    <jats:italic>pikR2<\/jats:italic>\n                    , is supported by\n                    <jats:italic>pikR1<\/jats:italic>\n                    and specifically induced by ketolides. The resistance mechanism remains fully functional when\n                    <jats:italic>pikR1<\/jats:italic>\n                    and\n                    <jats:italic>pikR2<\/jats:italic>\n                    are transferred to other bacterial species and affords protection against clinical ketolides. These findings emphasize the need for the preemptive development of antibiotics that can overcome this resistance mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1512090112","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T22:58:48Z","timestamp":1444085928000},"page":"12956-12961","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["Resistance to ketolide antibiotics by coordinated expression of rRNA methyltransferases in a bacterial producer of natural ketolides"],"prefix":"10.1073","volume":"112","author":[{"given":"Mashal M.","family":"Almutairi","sequence":"first","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Ryeol","family":"Park","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"V\u00e1zquez-Laslop","sequence":"additional","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Douthwaite","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Mankin","sequence":"additional","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.43.100189.001231"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35101544"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008685107"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007988107"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.577"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2984"},{"key":"e_1_3_3_7_2","volume-title":"Ribosomes: Structure, Function, and Dynamics","author":"V\u00e1zquez-Laslop N","year":"2011","unstructured":"N V\u00e1zquez-Laslop, H Ramu, AS Mankin, Nascent peptide\u2013mediated ribosome stalling promoted by antibiotics. 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