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Iron - A Key Nexus in the Virulence of Aspergillus fumigatus.
Front Microbiol 2012; 3:28FM

Abstract

Iron is an essential but, in excess, toxic nutrient. Therefore, fungi evolved fine-tuned mechanisms for uptake and storage of iron, such as the production of siderophores (low-molecular mass iron-specific chelators). In Aspergillus fumigatus, iron starvation causes extensive transcriptional remodeling involving two central transcription factors, which are interconnected in a negative transcriptional feed-back loop: the GATA-factor SreA and the bZip-factor HapX. During iron sufficiency, SreA represses iron uptake, including reductive iron assimilation and siderophore-mediated iron uptake, to avoid toxic effects. During iron starvation, HapX represses iron-consuming pathways, including heme biosynthesis and respiration, to spare iron and activates synthesis of ribotoxin AspF1 and siderophores, the latter partly by ensuring supply of the precursor, ornithine. In accordance with the expression pattern and mode of action, detrimental effects of inactivation of SreA and HapX are confined to growth during iron sufficiency and iron starvation, respectively. Deficiency in HapX, but not SreA, attenuates virulence of A. fumigatus in a murine model of aspergillosis, which underlines the crucial role of adaptation to iron limitation in virulence. Consistently, production of both extra and intracellular siderophores is crucial for virulence of A. fumigatus. Recently, the sterol regulatory element binding protein SrbA was found to be essential for adaptation to iron starvation, thereby linking regulation of iron metabolism, ergosterol biosynthesis, azole drug resistance, and hypoxia adaptation.

Authors+Show Affiliations

Division of Molecular Biology/Biocenter, Innsbruck Medical University Innsbruck, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22347220

Citation

Haas, Hubertus. "Iron - a Key Nexus in the Virulence of Aspergillus Fumigatus." Frontiers in Microbiology, vol. 3, 2012, p. 28.
Haas H. Iron - A Key Nexus in the Virulence of Aspergillus fumigatus. Front Microbiol. 2012;3:28.
Haas, H. (2012). Iron - A Key Nexus in the Virulence of Aspergillus fumigatus. Frontiers in Microbiology, 3, p. 28. doi:10.3389/fmicb.2012.00028.
Haas H. Iron - a Key Nexus in the Virulence of Aspergillus Fumigatus. Front Microbiol. 2012;3:28. PubMed PMID: 22347220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron - A Key Nexus in the Virulence of Aspergillus fumigatus. A1 - Haas,Hubertus, Y1 - 2012/02/06/ PY - 2011/12/06/received PY - 2012/01/16/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/2/22/medline KW - ergosterol KW - fungi KW - iron KW - isoprenoid KW - mevalonate KW - ornithine KW - siderophore KW - virulence SP - 28 EP - 28 JF - Frontiers in microbiology JO - Front Microbiol VL - 3 N2 - Iron is an essential but, in excess, toxic nutrient. Therefore, fungi evolved fine-tuned mechanisms for uptake and storage of iron, such as the production of siderophores (low-molecular mass iron-specific chelators). In Aspergillus fumigatus, iron starvation causes extensive transcriptional remodeling involving two central transcription factors, which are interconnected in a negative transcriptional feed-back loop: the GATA-factor SreA and the bZip-factor HapX. During iron sufficiency, SreA represses iron uptake, including reductive iron assimilation and siderophore-mediated iron uptake, to avoid toxic effects. During iron starvation, HapX represses iron-consuming pathways, including heme biosynthesis and respiration, to spare iron and activates synthesis of ribotoxin AspF1 and siderophores, the latter partly by ensuring supply of the precursor, ornithine. In accordance with the expression pattern and mode of action, detrimental effects of inactivation of SreA and HapX are confined to growth during iron sufficiency and iron starvation, respectively. Deficiency in HapX, but not SreA, attenuates virulence of A. fumigatus in a murine model of aspergillosis, which underlines the crucial role of adaptation to iron limitation in virulence. Consistently, production of both extra and intracellular siderophores is crucial for virulence of A. fumigatus. Recently, the sterol regulatory element binding protein SrbA was found to be essential for adaptation to iron starvation, thereby linking regulation of iron metabolism, ergosterol biosynthesis, azole drug resistance, and hypoxia adaptation. SN - 1664-302X UR - https://www.unboundmedicine.com/medline/citation/22347220/Iron___A_Key_Nexus_in_the_Virulence_of_Aspergillus_fumigatus_ L2 - https://dx.doi.org/10.3389/fmicb.2012.00028 DB - PRIME DP - Unbound Medicine ER -