{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:41:49Z","timestamp":1773416509892,"version":"3.50.1"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"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":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Candida glabrata<\/jats:italic>\n              is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other\n              <jats:italic>Candida<\/jats:italic>\n              spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an\n              <jats:italic>in vitro<\/jats:italic>\n              microevolution experiment, we found that loss-of-function mutants of the ATF\/CREB transcription factor\n              <jats:italic>CST6<\/jats:italic>\n              suppresses the fluconazole hyper-susceptibility of the\n              <jats:italic>upc2A<\/jats:italic>\n              \u2206 mutant. Here, we confirm that the\n              <jats:italic>cst6<\/jats:italic>\n              \u2206\n              <jats:italic>upc2A<\/jats:italic>\n              \u2206 mutants are resistant to fluconazole but not to hypoxia relative to the\n              <jats:italic>upc2A<\/jats:italic>\n              \u2206 mutant. Sterol analysis of these mutants indicates that this suppression phenotype is not due to restoration of ergosterol levels in the\n              <jats:italic>cst6<\/jats:italic>\n              \u2206\n              <jats:italic>upc2A<\/jats:italic>\n              \u2206 mutant. Furthermore, increased expression of\n              <jats:italic>CDR1<\/jats:italic>\n              , the efflux pump implicated in the vast majority of azole-resistant\n              <jats:italic>C. glabrata<\/jats:italic>\n              strains, does not account for the suppression phenotype. Instead, our data suggest that this effect is due in part to increased expression of the adhesin\n              <jats:italic>EPA3<\/jats:italic>\n              , which has been shown by others to reduce fluconazole susceptibility in\n              <jats:italic>C. glabrata<\/jats:italic>\n              . In addition, we find that loss of both\n              <jats:italic>UPC2A<\/jats:italic>\n              and\n              <jats:italic>CST6<\/jats:italic>\n              reduces the expression of mitochondrial and respiratory genes and that this also contributes to the suppression phenotype as well as to the resistance of\n              <jats:italic>cst6<\/jats:italic>\n              \u2206 to fluconazole. These latter data further emphasize the connection between mitochondrial function and azole susceptibility.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01294-24","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:01:42Z","timestamp":1734962502000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Genetic interaction analysis of\n            <i>Candida glabrata<\/i>\n            transcription factors\n            <i>CST6<\/i>\n            and\n            <i>UPC2A<\/i>\n            in the regulation of respiration and fluconazole susceptibility"],"prefix":"10.1128","volume":"69","author":[{"given":"Tomye L.","family":"Ollinger","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-1500","authenticated-orcid":true,"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin-Madison","place":["Madison, USA"]},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison","place":["Madison, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josie E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Molecular Biosciences Division, School of Biosciences, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Swansea University Medical School, Swansea University","place":["Swansea, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":true,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin-Madison","place":["Madison, USA"]},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison","place":["Madison, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Stamnes","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":true,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]},{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, The University of Iowa","place":["Iowa City, 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