{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:24:34Z","timestamp":1790364274260,"version":"4.1.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Overexpression of the multidrug efflux pump\n            <jats:italic>MDR1<\/jats:italic>\n            is one mechanism by which the pathogenic yeast\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n            develops resistance to the antifungal drug fluconazole. The constitutive upregulation of\n            <jats:italic>MDR1<\/jats:italic>\n            in fluconazole-resistant, clinical\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            isolates is caused by gain-of-function mutations in the zinc cluster transcription factor Mrr1. It has been suggested that Mrr1 activates\n            <jats:italic>MDR1<\/jats:italic>\n            transcription by recruiting Ada2, a subunit of the SAGA\/ADA coactivator complex. However,\n            <jats:italic>MDR1<\/jats:italic>\n            expression is also regulated by the bZIP transcription factor Cap1, which mediates the oxidative stress response in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            . Here, we show that a hyperactive Mrr1 containing a gain-of-function mutation promotes\n            <jats:italic>MDR1<\/jats:italic>\n            overexpression independently of Ada2. In contrast, a C-terminally truncated, hyperactive Cap1 caused\n            <jats:italic>MDR1<\/jats:italic>\n            overexpression in a wild-type strain but only weakly in mutants lacking\n            <jats:italic>ADA2<\/jats:italic>\n            . In the presence of benomyl or H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            , compounds that induce\n            <jats:italic>MDR1<\/jats:italic>\n            expression in an Mrr1- and Cap1-dependent fashion,\n            <jats:italic>MDR1<\/jats:italic>\n            was upregulated with the same efficiency in wild-type and\n            <jats:italic>ada2<\/jats:italic>\n            \u0394 cells. These results indicate that Cap1, but not Mrr1, recruits Ada2 to the\n            <jats:italic>MDR1<\/jats:italic>\n            promoter to induce the expression of this multidrug efflux pump and that Ada2 is not required for\n            <jats:italic>MDR1<\/jats:italic>\n            overexpression in fluconazole-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            strains containing gain-of-function mutations in Mrr1.\n          <\/jats:p>","DOI":"10.1128\/aac.03065-14","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T04:05:22Z","timestamp":1402977922000},"page":"5102-5110","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["SAGA\/ADA Complex Subunit Ada2 Is Required for Cap1- but Not Mrr1-Mediated Upregulation of the Candida albicans Multidrug Efflux Pump\n            <i>MDR1<\/i>"],"prefix":"10.1128","volume":"58","author":[{"given":"Bernardo","family":"Ram\u00edrez-Zavala","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Molekulare Infektionsbiologie, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selene","family":"Mogavero","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Infektionsbiologie, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Biology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sch\u00f6ller","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Infektionsbiologie, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Sasse","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Infektionsbiologie, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. David","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Morschh\u00e4user","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Infektionsbiologie, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.4.648"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01899.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002940050385"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.2785-2792.2005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3064-3079.2004"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.29277-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01343-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00002-09"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030164"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025623"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05100-11"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2009.08.002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06309.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00740-08"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.3.700-708.1999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00051-08"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/452541a"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-10-0899"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06836"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-11-1093"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2004.06.021"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.7.2331-2338.1997"},{"key":"e_1_3_2_24_2","volume-title":"Current protocols in molecular biology","author":"Ausubel F","year":"1989","unstructured":"AusubelFBrentRKingstonRMooreDSeidmanJSmithJStruhlK. 1989. 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