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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,8,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Better understanding of the mechanisms used by bacteria to counter antibacterial agents is essential to cope with the rising prevalence of antimicrobial resistance. Here, we identified the mechanism of resistance of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    to an antimycobacterial cyano-substituted fused pyrido-benzimidazole. Clones bearing mutations in a transcription factor, Rv2887, markedly up-regulated the expression of\n                    <jats:italic>rv0560c<\/jats:italic>\n                    , a putative methyltransferase. Rv0560c\n                    <jats:italic>N<\/jats:italic>\n                    -methylated the pyrido-benzimidazole in vitro and in\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , abrogating its bactericidal activity. Resistant mutants selected in the absence of\n                    <jats:italic>rv0560c<\/jats:italic>\n                    led to the identification of the target of the compound, the essential oxidoreductase, decaprenylphosphoryl-\u03b2-\n                    <jats:sc>d<\/jats:sc>\n                    -ribose 2-oxidase (DprE1). Methylation of an antibacterial compound is a previously uncharacterized mode of antimicrobial resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1606590113","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T22:18:28Z","timestamp":1468880308000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":91,"title":["<i>N<\/i>\n                    -methylation of a bactericidal compound as a resistance mechanism in\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1073","volume":"113","author":[{"given":"Thulasi","family":"Warrier","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanishk","family":"Kapilashrami","sequence":"additional","affiliation":[{"name":"Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New 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University of Massachusetts Medical School, Worcester, MA 01655;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumitha","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjie","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 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