Aspergillus spp.: ironing out iron problems

Ref ID: 18439

Author:

Hubertus Haas

Author address:

Division of Molecular Biology/Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck/Austria

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Iron is an essential but in excess toxic nutrient. Therefore, fungi evolved fine8208;tuned mechanisms for uptake and
storage of iron, such as the production of siderophores (low8208;molecular mass iron8208;specific chelators). In Aspergillus
fumigatus, iron starvation causes extensive transcriptional remodeling involving two central transcription factors,
which are interconnected in a negative transcriptional feed8208;back loop: the GATA8208;factor SreA and the bZip8208;factor
HapX. During iron sufficiency SreA represses iron uptake, including reductive iron assimilation and siderophore8208;
mediated iron uptake, to avoid toxic effects. During iron starvation HapX represses iron8208;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 agreement 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 extra8208;  and intracellular siderophores is crucial for virulence of A.
fumigatus. Recently, the sterol8208;regulatory element8208;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.

Abstract Number: PL4.2

Conference Year: 2012

Link to conference website: http://www.ecfg.info/images/Abstract_Book_Electronic.pdf

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