{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:59:03Z","timestamp":1791273543201,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"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":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Antifungal therapy failure can be associated with increased resistance to the employed antifungal agents.\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            , the second most common cause of invasive candidiasis, is intrinsically less susceptible to the azole class of antifungals and accounts for 15% of all\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n            bloodstream infections. Here, we show that\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            <jats:italic>MED2<\/jats:italic>\n            (\n            <jats:italic>CgMED2<\/jats:italic>\n            ), which codes for a tail subunit of the RNA polymerase II Mediator complex, is required for resistance to azole antifungal drugs 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            . An inability to transcriptionally activate genes encoding a zinc finger transcriptional factor, CgPdr1, and multidrug efflux pump, CgCdr1, primarily contributes to the elevated susceptibility of the\n            <jats:italic>Cgmed2<\/jats:italic>\n            \u0394 mutant toward azole antifungals. We also report for the first time that the\n            <jats:italic>Cgmed2<\/jats:italic>\n            \u0394 mutant exhibits sensitivity to caspofungin, a constitutively activated protein kinase C-mediated cell wall integrity pathway, and elevated adherence to epithelial cells. The increased adherence of the\n            <jats:italic>Cgmed2<\/jats:italic>\n            \u0394 mutant was attributed to the elevated expression of the\n            <jats:italic>EPA1<\/jats:italic>\n            and\n            <jats:italic>EPA7<\/jats:italic>\n            genes. Further, our data demonstrate that\n            <jats:italic>CgMED2<\/jats:italic>\n            is required for intracellular proliferation in human macrophages and modulates survival in a murine model of disseminated candidiasis. Lastly, we show an essential requirement for CgMed2, along with the Mediator middle subunit CgNut1 and the Mediator cyclin-dependent kinase\/cyclin subunit CgSrb8, for the high-level fluconazole resistance conferred by the hyperactive allele of CgPdr1. Together, our findings underscore a pivotal role for CgMed2 in basal tolerance and acquired resistance to azole antifungals.\n          <\/jats:p>","DOI":"10.1128\/aac.02786-14","type":"journal-article","created":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T06:34:28Z","timestamp":1406615668000},"page":"5976-5986","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Pivotal Role for a Tail Subunit of the RNA Polymerase II Mediator Complex CgMed2 in Azole Tolerance and Adherence in Candida glabrata"],"prefix":"10.1128","volume":"58","author":[{"given":"Sapan","family":"Borah","sequence":"first","affiliation":[{"name":"Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Shivarathri","sequence":"additional","affiliation":[{"name":"Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek Kumar","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9l\u00e8ne","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Sanglard","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00029-06"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01079-10"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc9239"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2013.09.005"},{"key":"e_1_3_3_6_2","first-page":"661","article-title":"Candidemia in intensive care unit: a nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013","volume":"18","author":"Montagna MT","year":"2014","unstructured":"MontagnaMTLoveroGBorghiEAmatoGAndreoniSCampionLLo CascioGLombardiGLuzzaroFMansoEMussapMPecilePPerinSTangorraETronciMIattaRMoraceG. 2014. 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