HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.

Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus. HapX represses iron-dependent and mitochon...

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Autores principales:	Markus Schrettl, Nicola Beckmann, John Varga, Thorsten Heinekamp, Ilse D Jacobsen, Christoph Jöchl, Tarek A Moussa, Shaohua Wang, Fabio Gsaller, Michael Blatzer, Ernst R Werner, William C Niermann, Axel A Brakhage, Hubertus Haas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/feac8ba4ae864815876ffffab965291f
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spelling	oai:doaj.org-article:feac8ba4ae864815876ffffab965291f2021-11-18T06:03:53ZHapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.1553-73661553-737410.1371/journal.ppat.1001124https://doaj.org/article/feac8ba4ae864815876ffffab965291f2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20941352/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus. HapX represses iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster and heme biosynthesis. In agreement with the impact on mitochondrial metabolism, HapX-deficiency decreases resistance to tetracycline and increases mitochondrial DNA content. Pathways positively affected by HapX include production of the ribotoxin AspF1 and siderophores, which are known virulence determinants. Iron starvation causes a massive remodeling of the amino acid pool and HapX is essential for the coordination of the production of siderophores and their precursor ornithine. Consistent with HapX-function being limited to iron depleted conditions and A. fumigatus facing iron starvation in the host, HapX-deficiency causes significant attenuation of virulence in a murine model of aspergillosis. Taken together, this study demonstrates that HapX-dependent adaption to conditions of iron starvation is crucial for virulence of A. fumigatus.Markus SchrettlNicola BeckmannJohn VargaThorsten HeinekampIlse D JacobsenChristoph JöchlTarek A MoussaShaohua WangFabio GsallerMichael BlatzerErnst R WernerWilliam C NiermannAxel A BrakhageHubertus HaasPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 9, p e1001124 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Markus Schrettl Nicola Beckmann John Varga Thorsten Heinekamp Ilse D Jacobsen Christoph Jöchl Tarek A Moussa Shaohua Wang Fabio Gsaller Michael Blatzer Ernst R Werner William C Niermann Axel A Brakhage Hubertus Haas HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
description	Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus. HapX represses iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster and heme biosynthesis. In agreement with the impact on mitochondrial metabolism, HapX-deficiency decreases resistance to tetracycline and increases mitochondrial DNA content. Pathways positively affected by HapX include production of the ribotoxin AspF1 and siderophores, which are known virulence determinants. Iron starvation causes a massive remodeling of the amino acid pool and HapX is essential for the coordination of the production of siderophores and their precursor ornithine. Consistent with HapX-function being limited to iron depleted conditions and A. fumigatus facing iron starvation in the host, HapX-deficiency causes significant attenuation of virulence in a murine model of aspergillosis. Taken together, this study demonstrates that HapX-dependent adaption to conditions of iron starvation is crucial for virulence of A. fumigatus.
format	article
author	Markus Schrettl Nicola Beckmann John Varga Thorsten Heinekamp Ilse D Jacobsen Christoph Jöchl Tarek A Moussa Shaohua Wang Fabio Gsaller Michael Blatzer Ernst R Werner William C Niermann Axel A Brakhage Hubertus Haas
author_facet	Markus Schrettl Nicola Beckmann John Varga Thorsten Heinekamp Ilse D Jacobsen Christoph Jöchl Tarek A Moussa Shaohua Wang Fabio Gsaller Michael Blatzer Ernst R Werner William C Niermann Axel A Brakhage Hubertus Haas
author_sort	Markus Schrettl
title	HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
title_short	HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
title_full	HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
title_fullStr	HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
title_full_unstemmed	HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.
title_sort	hapx-mediated adaption to iron starvation is crucial for virulence of aspergillus fumigatus.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/feac8ba4ae864815876ffffab965291f
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HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.

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