title: Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host.
abstract: The yeast Candida albicans transitions between distinct lifestyles as a normal component of the human gastrointestinal microbiome and the most common agent of disseminated fungal disease. We previously identified Sef1 as a novel Cys(6)Zn(2) DNA binding protein that plays an essential role in C. albicans virulence by activating the transcription of iron uptake genes in iron-poor environments such as the host bloodstream and internal organs. Conversely, in the iron-replete gastrointestinal tract, persistence as a commensal requires the transcriptional repressor Sfu1, which represses SEF1 and genes for iron uptake. Here, we describe an unexpected, transcription-independent role for Sfu1 in the direct inhibition of Sef1 function through protein complex formation and localization in the cytoplasm, where Sef1 is destabilized. Under iron-limiting conditions, Sef1 forms an alternative complex with the putative kinase, Ssn3, resulting in its phosphorylation, nuclear localization, and transcriptional activity. Analysis of sfu1 and ssn3 mutants in a mammalian model of disseminated candidiasis indicates that these post-transcriptional regulatory mechanisms serve as a means for precise titration of C. albicans virulence.
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Changbin
authors.initials: C
authors.lastname: Chen
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Noble
mesh_terms: D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D002177:Candidiasis / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005656:Fungal Proteins; D046912:Multiprotein Complexes; D007501:Iron; D018844:Cyclin-Dependent Kinases