{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:30:39Z","timestamp":1761129039824,"version":"3.40.4"},"reference-count":24,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemotherapy"],"published-print":{"date-parts":[[2012]]},"abstract":"<b><i>Background:<\/i><\/b> Intrinsic multidrug resistance of the <i>Mycobacterium avium<\/i>-<i>intracellulare<\/i> complex presents a serious problem in the treatment of the diseases caused by these bacteria. Recently, it was shown that deletion of a polyketide synthase, Pks12, in an <i>M. avium<\/i> laboratory strain decreases this intrinsic resistance. <b><i>Methods:<\/i><\/b> We investigated Pks12 expression and its enzymatic activity in 9 clinical isolates of <i>M. intracellulare<\/i>, and compared their drug susceptibilities to 4 drugs. Also, we made <i>pks12<\/i>-disrupted <i>M. bovis<\/i> bacillus Calmette-Gu\u00e9rin (BCG) mutant and its complemented strain. Using these BCG and <i>M. intracellulare<\/i> strains, we observed intracellular accumulation of ethidium bromide (EtBr). <b><i>Results:<\/i><\/b> We found positive correlations between Pks12 and drug resistance for all of the antibiotics tested. The drug susceptible <i>M. intracellulare<\/i> strain showed higher EtBr accumulation. Consistent with this, EtBr was much more accumulated in <i>pks12<\/i>-disrupted BCG than wild-type or the complemented strains. <b><i>Conclusions:<\/i><\/b> Collectively, these results suggest that Pks12 controls the multidrug resistance in part through intracellular drug accumulation.<\/jats:p>","DOI":"10.1159\/000343311","type":"journal-article","created":{"date-parts":[[2012,11,16]],"date-time":"2012-11-16T08:15:37Z","timestamp":1353053737000},"page":"341-348","source":"Crossref","is-referenced-by-count":8,"title":["The Polyketide Synthase-Associated Multidrug Tolerance in <b><i>Mycobacterium intracellulare<\/i><\/b> Clinical Isolates"],"prefix":"10.1159","volume":"58","author":[{"given":"Isamu","family":"Matsunaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Meda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noboru","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagatoshi","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2012,11,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1378%2Fchest.07-0358"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10096-011-1326-7"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038%2F35009119"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1084%2Fjem.20041429"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1128%2FAAC.48.9.3412-3418.2004"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1089353"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.chembiol.2007.09.010"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1093%2Fjac%2Fdkn070"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1159%2F000321484"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1159%2F000109769"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159%2F000226425"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1186%2F1471-2180-11-35"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1159%2F000330858"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1128%2FCMR.17.1.98-106.2004"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1164%2Frccm.200603-450OC"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1093%2Fjac%2Fdkq536"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1128%2FAAC.01577-08"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.ijantimicag.2009.07.010"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1093%2Fjac%2Fdkn178"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1128%2FJB.01132-08"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1128%2FAAC.48.7.2415-2423.2004"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1128%2FJB.01046-07"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1155%2F2012%2F981821"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1099%2Fjmm.0.012864-0"}],"container-title":["Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/343311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/343311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:23:36Z","timestamp":1745432616000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000343311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":24,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,1,1]]},"published-print":{"date-parts":[[2013,1,23]]}},"URL":"https:\/\/doi.org\/10.1159\/000343311","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5241490","asserted-by":"subject"}]},"ISSN":["0009-3157","1421-9794"],"issn-type":[{"type":"print","value":"0009-3157"},{"type":"electronic","value":"1421-9794"}],"subject":[],"published":{"date-parts":[[2012]]}}}