HapX-Mediated Adaption to Iron Starvation Is Crucial for Virulence of Aspergillus fumigatus: e1001124
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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| Veröffentlicht in: | PLoS pathogens 2010-09, Vol.6 (9) |
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| creator | Schrettl, Markus Beckmann, Nicola Varga, John Heinekamp, Thorsten Jacobsen, Ilse D Jöchl, Christoph Moussa, Tarek A Wang, Shaohua Gsaller, Fabio Blatzer, Michael Werner, Ernst R Niermann, William C Brakhage, Axel A Haas, Hubertus |
| 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. |
| doi_str_mv | 10.1371/journal.ppat.1001124 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1001124</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Amino acids ; Biosynthesis ; Composting ; Enzymes ; Experiments ; Fungi ; Immune system ; Metabolism ; Mitochondrial DNA</subject><ispartof>PLoS pathogens, 2010-09, Vol.6 (9)</ispartof><rights>2010 Schrettl et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Schrettl M, Beckmann N, Varga J, Heinekamp T, Jacobsen ID, et al. (2010) HapX-Mediated Adaption to Iron Starvation Is Crucial for Virulence of Aspergillus fumigatus. 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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. 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| subjects | Amino acids Biosynthesis Composting Enzymes Experiments Fungi Immune system Metabolism Mitochondrial DNA |
| title | HapX-Mediated Adaption to Iron Starvation Is Crucial for Virulence of Aspergillus fumigatus: e1001124 |
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