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

PLoS Pathogens

Suzanne M. Noble¹  Changbin Chen¹ 

[1] Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California, United States of America

关键词: C;    ida albicans;    Virulence factors;    Cytoplasm;    DNA transcription;    Phosphorylation;    Immunoblotting;    Hyperexpression techniques;    Transcriptional control;   

DOI  :  10.1371/journal.ppat.1002956

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY