Post-Transcriptional Regulation of the Sef1 Transcription Factor Controls the Virulence of Candida albicans in Its Mammalian Host

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 cys6zn2 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. © 2012 chen,noble.