{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:14:40Z","timestamp":1785942880645,"version":"3.56.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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":["R01AI177254"],"award-info":[{"award-number":["R01AI177254"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Candida albicans<\/jats:italic>\n is one of the most common causes of human fungal disease. An intensively studied\n C. albicans<\/jats:italic>\n virulence traits is its ability to adopt both yeast and filamentous morphologies. Accordingly, the regulation of the yeast-to-filament transition has been an area of intense study in medical mycology. A long-standing mechanistic paradigm in this field is that the cAMP-protein kinase A pathway phosphorylates a master transcriptional regulator of\n C. albicans<\/jats:italic>\n filamentation, Efg1, to drive filamentation. This model has been generalized over the years despite the fact that the initial work showed that it applied to only specific\n in vitro<\/jats:italic>\n filamentation conditions. Here, we reinvestigated the protein kinase A-Efg1 paradigm by generating new strains containing alleles of\n EFG1<\/jats:italic>\n with the putative protein kinase A phosphorylation site (T208) mutated to either Ala or Glu which blocks or mimics phosphorylation, respectively. We integrated these alleles into\n efg1<\/jats:italic>\n \u2206\u2206 mutants so that they are expressed from the endogenous promoter. We assayed the effect of these Efg1 mutations on (i)\n in vitro<\/jats:italic>\n filamentation under a wide range of inducing conditions, (ii) biofilm formation, (iii)\n in vivo<\/jats:italic>\n filamentation, (iv) virulence in a model of disseminated candidiasis, and (v) gene expression during\n in vitro<\/jats:italic>\n filamentation. Using updated genetic approaches, we found no evidence that blocking or mimicking protein kinase phosphorylation of Efg1 affected its function during filamentation, biofilm formation, or infection. Therefore, additional studies will be required to identify the mechanisms by which Efg1 is regulated during hyphal morphogenesis.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Candida albicans<\/jats:italic>\n is a common human fungal pathogen causing both superficial mucosal and life-threatening invasive disease. The virulence of\n C. albicans<\/jats:italic>\n is associated with its ability to form filamentous hyphae and pseudohyphae. The regulation of this process is widely attributed to the phosphorylation of a transcription factor Efg1 by the protein kinase A signaling pathway. Since its initial description 25 years ago, this model has informed the design and interpretation of many studies of\n C. albicans<\/jats:italic>\n . Through the use of updated genetic methods, we have found that protein kinase A-mediated phosphorylation of Efg1 is dispensable for filamentation, biofilm formation, and virulence in an experimental model of candidiasis. Although these data are negative in nature, the centrality of the protein kinase A-Efg1 paradigm to\n C. albicans<\/jats:italic>\n pathogenesis studies increases their impact and should catalyze new studies to understand how this master regulator of\n C. albicans<\/jats:italic>\n biology is itself regulated.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/mbio.02913-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:00:08Z","timestamp":1761915608000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["The\n Candida albicans<\/i>\n transcription factor Efg1 governs hyphal morphogenesis independently of the cAMP-protein kinase A pathway"],"prefix":"10.1128","volume":"16","author":[{"given":"Juraj","family":"Kramara","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan S.","family":"Wakade","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Frazer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gq02987","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Stamnes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-484X","authenticated-orcid":true,"given":"Richard J.","family":"Bennett","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gq02987","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":true,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]},{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa","place":["Iowa City, 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