{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:10:37Z","timestamp":1778260237258,"version":"3.51.4"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The widespread emergence of antifungal drug resistance poses a severe clinical problem. Though predicted to play a role in this phenomenon, the drug:H\n            <jats:sup>+<\/jats:sup>\n            antiporters (DHA) of the major facilitator superfamily have largely escaped characterization in pathogenic yeasts. This work describes the first DHA from the pathogenic yeast\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida glabrata<\/jats:named-content>\n            reported to be involved in antifungal drug resistance, the\n            <jats:italic>C. glabrata QDR2<\/jats:italic>\n            (\n            <jats:italic>CgQDR2<\/jats:italic>\n            ) gene (ORF\n            <jats:italic>CAGL0G08624g<\/jats:italic>\n            ). The expression of\n            <jats:italic>CgQDR2<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            was found to confer resistance to the antifungal drugs miconazole, tioconazole, clotrimazole, and ketoconazole. By use of a green fluorescent protein (GFP) fusion, the CgQdr2 protein was found to be targeted to the plasma membrane in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            . In agreement with these observations,\n            <jats:italic>CgQDR2<\/jats:italic>\n            expression was found to decrease the intracellular accumulation of radiolabeled clotrimazole in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            and to play a role in the extrusion of this antifungal from preloaded cells. Interestingly, the functional heterologous expression of\n            <jats:italic>CgQDR2<\/jats:italic>\n            in the model yeast\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>\n            further confirmed the role of this gene as a multidrug resistance determinant: its expression was able to complement the susceptibility phenotype exhibited by its\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. cerevisiae<\/jats:named-content>\n            homologue,\n            <jats:italic>QDR2<\/jats:italic>\n            , in the presence of imidazoles and of the antimalarial and antiarrhythmic drug quinidine. In contrast to the findings reported for Qdr2, CgQdr2 expression does not contribute to the ability of yeast to grow under K\n            <jats:sup>+<\/jats:sup>\n            -limiting conditions. Interestingly,\n            <jats:italic>CgQDR2<\/jats:italic>\n            transcript levels were seen to be upregulated in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            cells challenged with clotrimazole or quinidine. This upregulation was found to depend directly on the transcription factor CgPdr1, the major regulator of multidrug resistance in this pathogenic yeast, which has also been found to be a determinant of quinidine and clotrimazole resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00811-12","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T03:01:41Z","timestamp":1367290901000},"page":"3159-3167","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["Candida glabrata Drug:H\n            <sup>+<\/sup>\n            Antiporter CgQdr2 Confers Imidazole Drug Resistance, Being Activated by Transcription Factor CgPdr1"],"prefix":"10.1128","volume":"57","author":[{"given":"Catarina","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]},{"given":"Carla","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]},{"given":"T\u00e2nia R.","family":"Cabrito","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]},{"given":"Adeline","family":"Renaudin","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]},{"given":"Michiyo","family":"Ohno","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center (MMRC), Chiba University, Chiba, Japan"}]},{"given":"Hiroji","family":"Chibana","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center (MMRC), Chiba University, Chiba, Japan"}]},{"given":"Isabel","family":"S\u00e1-Correia","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]},{"given":"Miguel C.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Technical University of Lisbon, Lisbon, Portugal"},{"name":"IBB\u2014Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T\u00e9cnico, Lisbon, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.6.1526"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.1.80"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1556\/amicr.54.2007.3.1"},{"key":"e_1_3_2_5_2","volume-title":"Molecular genetics of drug resistance","author":"Hayes JD","year":"1997","unstructured":"HayesJD WolfCR (ed). 1997. 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