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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans Tup1 filamentation fungal virulence gene regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/92ada380a5544ab2b0f537336c459272
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:92ada380a5544ab2b0f537336c459272
record_format	dspace
spelling	oai:doaj.org-article:92ada380a5544ab2b0f537336c4592722021-11-15T15:57:02ZAhr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mBio.00206-202150-7511https://doaj.org/article/92ada380a5544ab2b0f537336c4592722020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00206-20https://doaj.org/toc/2150-7511ABSTRACT 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.Sophia RubenEnrico GarbeSelene MogaveroDaniela Albrecht-EckardtDaniela HellwigAntje HäderThomas KrügerKatrin GerthIlse D. JacobsenOsama ElshafeeSascha BrunkeKerstin HünnigerOlaf KniemeyerAxel A. BrakhageJoachim MorschhäuserBernhard HubeSlavena VylkovaOliver KurzaiRonny MartinAmerican Society for MicrobiologyarticleCandida albicansTup1filamentationfungal virulencegene regulationMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Tup1 filamentation fungal virulence gene regulation Microbiology QR1-502
spellingShingle	Candida albicans Tup1 filamentation fungal virulence gene regulation Microbiology QR1-502 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>
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.
format	article
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
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_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_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_sort	ahr1 and tup1 contribute to the transcriptional control of virulence-associated genes in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/92ada380a5544ab2b0f537336c459272
work_keys_str_mv	AT sophiaruben ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT enricogarbe ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT selenemogavero ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT danielaalbrechteckardt ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT danielahellwig ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT antjehader ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT thomaskruger ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT katringerth ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT ilsedjacobsen ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT osamaelshafee ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT saschabrunke ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT kerstinhunniger ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT olafkniemeyer ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT axelabrakhage ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT joachimmorschhauser ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT bernhardhube ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT slavenavylkova ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT oliverkurzai ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent AT ronnymartin ahr1andtup1contributetothetranscriptionalcontrolofvirulenceassociatedgenesinnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontent
_version_	1718427040208650240

Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in <named-content content-type="genus-species">Candida albicans</named-content>

Ejemplares similares