{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:53:32Z","timestamp":1790780012424,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI146103"],"award-info":[{"award-number":["R01 AI146103"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007699","name":"University of Georgia","doi-asserted-by":"publisher","award":["Distinguished Research Professorship"],"award-info":[{"award-number":["Distinguished Research Professorship"]}],"id":[{"id":"10.13039\/100007699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The microbiome-associated fungus\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      is an opportunistic pathogen. Virulence traits include its ability to produce biofilm, a surface-associated growth form that persists on mucosae and implanted medical devices.\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      clinical isolates vary in ability to produce biofilm and the constituent filamentous cell types. Here, we focus on two transcription factors that promote filamentation and biofilm formation, Ndt80 and Ume6. We address two questions. First, how variable is the impact of Ndt80 among\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      strains? Second, what is the genetic interaction between\n                      <jats:italic toggle=\"yes\">NDT80<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      ? We find that Ndt80 is required for filamentation and biofilm formation in five clinical isolates in addition to the reference strain SC5314, where Ndt80 function has been well established. RNA-sequencing (RNA-seq) data indicate that\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      RNA levels are reduced in an\n                      <jats:italic toggle=\"yes\">ndt80<\/jats:italic>\n                      \u0394\/\u0394 mutant, possibly a result of altered\n                      <jats:italic toggle=\"yes\">RME1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">WOR1<\/jats:italic>\n                      expression, both of which control\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      . Increased expression of\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">ndt80<\/jats:italic>\n                      \u0394\/\u0394 mutants of three strain backgrounds restores filamentation and biofilm formation, though RNA-seq assays indicate that it does not suppress the overall\n                      <jats:italic toggle=\"yes\">ndt80<\/jats:italic>\n                      \u0394\/\u0394 gene expression defect. Ndt80 has an additional role in promoting tolerance to the antifungal drug fluconazole, an inhibitor of ergosterol synthesis. This\n                      <jats:italic toggle=\"yes\">ndt80<\/jats:italic>\n                      \u0394\/\u0394 phenotype varies considerably among clinical isolates. In three strains tested, increased expression of\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      in\n                      <jats:italic toggle=\"yes\">ndt80<\/jats:italic>\n                      \u0394\/\u0394 mutants enhances their susceptibility to fluconazole. Therefore, our results show an unexpected relationship between Ume6 expression and azole drug sensitivity. To our knowledge, Ume6 has previously been understood to function only in filamentation, biofilm formation, and related processes.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Our focus is the fungal pathogen\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        . Two traits, biofilm\/hypha formation and azole resistance, are major drivers of its infection ability. We examine the roles of two biofilm transcriptional regulators, Ndt80 and Ume6, in several\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        clinical isolates. Prior studies in one strain background (SC5314) indicated that Ndt80 controls both biofilm\/hypha formation and azole drug susceptibility and that Ume6 controls biofilm\/hypha formation. The four new findings here are that (i) Ndt80 effects on fluconazole sensitivity vary considerably with strain background; (ii) Ndt80 is required for filamentation and biofilm formation in multiple clinical isolates; (iii) the Ndt80 target Ume6 contributes to Ndt80 control of filamentation and biofilm formation in multiple clinical isolates; and (iv) Ume6 influences fluconazole vulnerability, the first Ume6 function to our knowledge that is unrelated to filamentation.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00014-26","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:00:18Z","timestamp":1774616418000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Impact of\n                    <i>Candida albicans NDT80<\/i>\n                    and\n                    <i>UME6<\/i>\n                    on biofilm formation and fluconazole susceptibility"],"prefix":"10.1128","volume":"11","author":[{"given":"Katharina","family":"Goerlich","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-4000","authenticated-orcid":true,"given":"Aaron P.","family":"Mitchell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Georgia","place":["Athens, 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