{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:31Z","timestamp":1791277891393,"version":"4.1.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,24]]},"abstract":"<jats:p>\n                    The emergence of multidrug-resistant (MDR) tuberculosis (TB) highlights the urgent need to understand the mechanisms of resistance to the drugs used to treat this disease. The aminoglycosides kanamycin and amikacin are important bactericidal drugs used to treat MDR TB, and resistance to one or both of these drugs is a defining characteristic of extensively drug-resistant TB. We identified mutations in the \u221210 and \u221235 promoter region of the\n                    <jats:italic>eis<\/jats:italic>\n                    gene, which encodes a previously uncharacterized aminoglycoside acetyltransferase. These mutations led to a 20\u2013180-fold increase in the amount of\n                    <jats:italic>eis<\/jats:italic>\n                    leaderless mRNA transcript, with a corresponding increase in protein expression. Importantly, these promoter mutations conferred resistance to kanamycin [5 \u03bcg\/mL &lt; minimum inhibitory concentration (MIC) \u226440 \u03bcg\/mL] but not to amikacin (MIC &lt;4 \u03bcg\/mL). Additionally, 80% of clinical isolates examined in this study that exhibited low-level kanamycin resistance harbored\n                    <jats:italic>eis<\/jats:italic>\n                    promoter mutations. These results have important clinical implications in that clinical isolates determined to be resistant to kanamycin may not be cross-resistant to amikacin, as is often assumed. Molecular detection of\n                    <jats:italic>eis<\/jats:italic>\n                    mutations should distinguish strains resistant to kanamycin and those resistant to kanamycin and amikacin. This may help avoid excluding a potentially effective drug from a treatment regimen for drug-resistant TB.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0907925106","type":"journal-article","created":{"date-parts":[[2009,11,11]],"date-time":"2009-11-11T22:19:33Z","timestamp":1257977973000},"page":"20004-20009","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":308,"title":["Overexpression of the chromosomally encoded aminoglycoside acetyltransferase\n                    <i>eis<\/i>\n                    confers kanamycin resistance in\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1073","volume":"106","author":[{"given":"M. Analise","family":"Zaunbrecher","sequence":"first","affiliation":[{"name":"Microbiology and Molecular Genetics Graduate Program, Department of Microbiology and Immunology, Rollins Research Center, Emory University, Atlanta, GA 30322; and"},{"name":"Division of TB Elimination, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"R. David","family":"Sikes","sequence":"additional","affiliation":[{"name":"Division of TB Elimination, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Metchock","sequence":"additional","affiliation":[{"name":"Division of TB Elimination, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Shinnick","sequence":"additional","affiliation":[{"name":"Division of TB Elimination, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Division of TB Elimination, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,24]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"Antituberculosis Drug Resistance in the World Report No. 4","year":"2008","unstructured":"Antituberculosis Drug Resistance in the World Report No. 4 (World Health Organization, Geneva, 2008)."},{"key":"e_1_3_3_2_2","first-page":"301","article-title":"Emergence of Mycobacterium tuberculosis with extensive resistance to second line drugs-worldwide, 2000\u20132004","volume":"55","year":"2006","unstructured":", Emergence of Mycobacterium tuberculosis with extensive resistance to second line drugs-worldwide, 2000\u20132004. 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