Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content>
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
Affiliations
Sophia Ruben
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Enrico Garbe
Research Group Host Fungal Interfaces, Septomics Research Centre, Friedrich Schiller University, Jena, Germany
Selene Mogavero
Department Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Daniela Albrecht-Eckardt
Biocontrol Jena GmbH, Jena, Germany
Daniela Hellwig
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Antje Häder
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Thomas Krüger
Department Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Katrin Gerth
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Ilse D. Jacobsen
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Osama Elshafee
Department Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Sascha Brunke
Department Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Kerstin Hünniger
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Olaf Kniemeyer
Department Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Axel A. Brakhage
Department Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Joachim Morschhäuser
Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany
Bernhard Hube
Department Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Slavena Vylkova
Research Group Host Fungal Interfaces, Septomics Research Centre, Friedrich Schiller University, Jena, Germany
Oliver Kurzai
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
Ronny Martin
Research Group Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knoell Institute, Jena, Germany
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.
