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...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002956&type=printable |
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| author | Changbin Chen Suzanne M Noble |
| author_facet | Changbin Chen Suzanne M Noble |
| author_sort | Changbin Chen |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-e09651baf19f462d8f7f69c7d37bdf2a |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-e09651baf19f462d8f7f69c7d37bdf2a2025-08-20T03:11:54ZengPublic 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002956&type=printable |
| 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 |
| title | 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_short | 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002956&type=printable |
| work_keys_str_mv | AT changbinchen posttranscriptionalregulationofthesef1transcriptionfactorcontrolsthevirulenceofcandidaalbicansinitsmammalianhost AT suzannemnoble posttranscriptionalregulationofthesef1transcriptionfactorcontrolsthevirulenceofcandidaalbicansinitsmammalianhost |