Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content>
ABSTRACT The capacity of Candida albicans to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes ALS3 and ECE1, which are involved in pathogenicity processes such as invasion, iron acquisiti...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00206-20 |
| _version_ | 1818424716795314176 |
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| author | Sophia Ruben Enrico Garbe Selene Mogavero Daniela Albrecht-Eckardt Daniela Hellwig Antje Häder Thomas Krüger Katrin Gerth Ilse D. Jacobsen Osama Elshafee Sascha Brunke Kerstin Hünniger Olaf Kniemeyer Axel A. Brakhage Joachim Morschhäuser Bernhard Hube Slavena Vylkova Oliver Kurzai Ronny Martin |
| author_facet | Sophia Ruben Enrico Garbe Selene Mogavero Daniela Albrecht-Eckardt Daniela Hellwig Antje Häder Thomas Krüger Katrin Gerth Ilse D. Jacobsen Osama Elshafee Sascha Brunke Kerstin Hünniger Olaf Kniemeyer Axel A. Brakhage Joachim Morschhäuser Bernhard Hube Slavena Vylkova Oliver Kurzai Ronny Martin |
| author_sort | Sophia Ruben |
| collection | DOAJ |
| description | ABSTRACT The capacity of Candida albicans to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes ALS3 and ECE1, which are involved in pathogenicity processes such as invasion, iron acquisition, and host cell damage. The global repressor Tup1 and its cofactor Nrg1 are considered to be the main antagonists of hyphal development in C. albicans. However, our experiments revealed that Tup1, but not Nrg1, was required for full expression of ALS3 and ECE1. In contrast to NRG1, overexpression of TUP1 was found to inhibit neither filamentous growth nor transcription of ALS3 and ECE1. In addition, we identified the transcription factor Ahr1 as being required for full expression of both genes. A hyperactive version of Ahr1 bound directly to the promoters of ALS3 and ECE1 and induced their transcription even in the absence of environmental stimuli. This regulation worked even in the absence of the crucial hyphal growth regulators Cph1 and Efg1 but was dependent on the presence of Tup1. Overall, our results show that Ahr1 and Tup1 are key contributors in the complex regulation of virulence-associated genes in the different C. albicans morphologies. IMPORTANCE Candida albicans is a major human fungal pathogen and the leading cause of systemic Candida infections. In recent years, Als3 and Ece1 were identified as important factors for fungal virulence. Transcription of both corresponding genes is closely associated with hyphal growth. Here, we describe how Tup1, normally a global repressor of gene expression as well as of filamentation, and the transcription factor Ahr1 contribute to full expression of ALS3 and ECE1 in C. albicans hyphae. Both regulators are required for high mRNA amounts of the two genes to ensure functional relevant protein synthesis and localization. These observations identified a new aspect of regulation in the complex transcriptional control of virulence-associated genes in C. albicans. |
| first_indexed | 2024-12-14T14:02:28Z |
| format | Article |
| id | doaj.art-92ada380a5544ab2b0f537336c459272 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T14:02:28Z |
| publishDate | 2020-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-92ada380a5544ab2b0f537336c4592722022-12-21T22:58:42ZengAmerican Society for MicrobiologymBio2150-75112020-04-0111210.1128/mBio.00206-20Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content>Sophia Ruben0Enrico Garbe1Selene Mogavero2Daniela Albrecht-Eckardt3Daniela Hellwig4Antje Häder5Thomas Krüger6Katrin Gerth7Ilse D. Jacobsen8Osama Elshafee9Sascha Brunke10Kerstin Hünniger11Olaf Kniemeyer12Axel A. Brakhage13Joachim Morschhäuser14Bernhard Hube15Slavena Vylkova16Oliver Kurzai17Ronny Martin18Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Host Fungal Interfaces, Septomics Research Centre, Friedrich Schiller University, Jena, GermanyDepartment Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyBiocontrol Jena GmbH, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyDepartment Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyDepartment Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyDepartment Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyDepartment Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyDepartment Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyInstitute for Molecular Infection Biology, University of Würzburg, Würzburg, GermanyDepartment Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Host Fungal Interfaces, Septomics Research Centre, Friedrich Schiller University, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyResearch Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, GermanyABSTRACT The capacity of Candida albicans to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes ALS3 and ECE1, which are involved in pathogenicity processes such as invasion, iron acquisition, and host cell damage. The global repressor Tup1 and its cofactor Nrg1 are considered to be the main antagonists of hyphal development in C. albicans. However, our experiments revealed that Tup1, but not Nrg1, was required for full expression of ALS3 and ECE1. In contrast to NRG1, overexpression of TUP1 was found to inhibit neither filamentous growth nor transcription of ALS3 and ECE1. In addition, we identified the transcription factor Ahr1 as being required for full expression of both genes. A hyperactive version of Ahr1 bound directly to the promoters of ALS3 and ECE1 and induced their transcription even in the absence of environmental stimuli. This regulation worked even in the absence of the crucial hyphal growth regulators Cph1 and Efg1 but was dependent on the presence of Tup1. Overall, our results show that Ahr1 and Tup1 are key contributors in the complex regulation of virulence-associated genes in the different C. albicans morphologies. IMPORTANCE Candida albicans is a major human fungal pathogen and the leading cause of systemic Candida infections. In recent years, Als3 and Ece1 were identified as important factors for fungal virulence. Transcription of both corresponding genes is closely associated with hyphal growth. Here, we describe how Tup1, normally a global repressor of gene expression as well as of filamentation, and the transcription factor Ahr1 contribute to full expression of ALS3 and ECE1 in C. albicans hyphae. Both regulators are required for high mRNA amounts of the two genes to ensure functional relevant protein synthesis and localization. These observations identified a new aspect of regulation in the complex transcriptional control of virulence-associated genes in C. albicans.https://journals.asm.org/doi/10.1128/mBio.00206-20Candida albicansTup1filamentationfungal virulencegene regulation |
| spellingShingle | Sophia Ruben Enrico Garbe Selene Mogavero Daniela Albrecht-Eckardt Daniela Hellwig Antje Häder Thomas Krüger Katrin Gerth Ilse D. Jacobsen Osama Elshafee Sascha Brunke Kerstin Hünniger Olaf Kniemeyer Axel A. Brakhage Joachim Morschhäuser Bernhard Hube Slavena Vylkova Oliver Kurzai Ronny Martin Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> mBio Candida albicans Tup1 filamentation fungal virulence gene regulation |
| title | Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_full | Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_fullStr | Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_full_unstemmed | Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_short | Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_sort | ahr1 and tup1 contribute to the transcriptional control of virulence associated genes in named content content type genus species candida albicans named content |
| topic | Candida albicans Tup1 filamentation fungal virulence gene regulation |
| url | https://journals.asm.org/doi/10.1128/mBio.00206-20 |
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