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 Cys(6)Zn(2) DNA binding protein that plays an essential role in C. albi...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC3486892?pdf=render |
id |
doaj-e09651baf19f462d8f7f69c7d37bdf2a |
---|---|
record_format |
Article |
spelling |
doaj-e09651baf19f462d8f7f69c7d37bdf2a2020-11-25T00:12:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-01811e100295610.1371/journal.ppat.1002956Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host.Changbin ChenSuzanne M NobleThe 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.http://europepmc.org/articles/PMC3486892?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Changbin Chen Suzanne M Noble |
spellingShingle |
Changbin Chen Suzanne M Noble Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. PLoS Pathogens |
author_facet |
Changbin Chen Suzanne M Noble |
author_sort |
Changbin Chen |
title |
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. |
title_short |
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. |
title_full |
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. |
title_fullStr |
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. |
title_full_unstemmed |
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host. |
title_sort |
post-transcriptional regulation of the sef1 transcription factor controls the virulence of candida albicans in its mammalian host. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3486892?pdf=render |
work_keys_str_mv |
AT changbinchen posttranscriptionalregulationofthesef1transcriptionfactorcontrolsthevirulenceofcandidaalbicansinitsmammalianhost AT suzannemnoble posttranscriptionalregulationofthesef1transcriptionfactorcontrolsthevirulenceofcandidaalbicansinitsmammalianhost |
_version_ |
1725400225610203136 |