{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:23:18Z","timestamp":1789507398298,"version":"build-2803163510"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"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":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Azole antifungal agents such as fluconazole exhibit fungistatic activity against\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            . Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of\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 disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1371\/journal.pgen.1000783\">http:\/\/dx.doi.org\/10.1371\/journal.pgen.1000783<\/jats:ext-link>\n            ), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes,\n            <jats:italic>UPC2<\/jats:italic>\n            , was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (\n            <jats:italic>CAS5<\/jats:italic>\n            ) was unable to recover from fluconazole exposure at concentrations as low as 2 \u03bcg\/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 \u03bcg\/ml fluconazole, and exhibited increased susceptibility by time-kill analysis.\n            <jats:italic>CAS5<\/jats:italic>\n            disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However,\n            <jats:italic>CAS5<\/jats:italic>\n            disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of\n            <jats:italic>CAS5<\/jats:italic>\n            in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of\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            to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals.\n          <\/jats:p>","DOI":"10.1128\/aac.00064-14","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T12:54:02Z","timestamp":1409748842000},"page":"6807-6818","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Disruption of the Transcriptional Regulator Cas5 Results in Enhanced Killing of Candida albicans by Fluconazole"],"prefix":"10.1128","volume":"58","author":[{"given":"Erin M.","family":"Vasicek","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Berkow","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P.","family":"Wiederhold","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine S.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. David","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Memphis, Tennessee, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-009-0021-y"},{"key":"e_1_3_3_3_2","first-page":"1375","volume-title":"Pharmacotherapy principles & practice","author":"Lewis RE","year":"2010","unstructured":"LewisRERogersPD. 2010. Invasive fungal infections, p 1375\u20131393. In Chisholm-BurnsMASchwinghammerTLWellsBGMalonePMKolesarJMDiPiroJT (ed), Pharmacotherapy principles & practice, 2nd ed. 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