SREA deficiency leads to derepression of siderophore transport, intracellular siderophore accumulation and oxidative stress in Aspergillus nidulans

Hubertus Haas, Harald Oberegger, Michelle Schoeser, Beate Abt, and Ivo Zadra

Author address: 

Department of Microbiology, University of Innsbruck (Med. School), Innsbruck, Austria

Abstract: 

Under conditions of iron deficiency most fungi excrete siderophores - low molecular-mass ferric iron chelators - in order to mobilize extracellular iron. In A. nidulans, siderophore biosynthesis has been shown to be negatively regulated by the GATA-type transcription factor SREA. Furthermore, lack of SREA leads to derepression of siderophore uptake and metabolization (e.g. siderophore hydrolysis by ornithine esterase) as well as increased accumulation of ferricrocin, the siderophore responsible for intracellular iron storage. In sreA-deletion strains, derepression of extracellular siderophore production is only partial, indicating the presence of additional iron regulatory mechanisms. In contrast to siderophore excretion, ferricrocin accumulation is positively affected by the external iron availability suggesting a protective role of this siderophore in detoxification of intracellular iron excess. The harmfulness of deregulated iron uptake in this mutant is demonstrated by increased expression of genes encoding the antioxidative enzymes superoxide dismutases SODA and SODB and catalase CATB. Noteworthy, expression of catB was found to be repressed by iron starvation in wild type and sreA-mutant strains consistent with catB being subject to positive iron regulation. Differential display led to identification of the putative SREA target genes amc-1 and mirA. Since amc-1 encodes a puative mitochondrial carrier for the siderophore component ornithine, cross regulation of siderophore biosynthesis and ornithine metabolism is indicated. The deduced MIRA amino acid sequence displays significant similarity to recently characterized siderophore permeases of Saccharomyces cerevisiae. Northern analysis confirmed iron-dependent expression of amc-1 and mirA and the role of SREA as a repressor of gene expression. These data demonstrate that SREA regulates a variety of processes involved in siderophore metabolism and show that increased iron uptake leads to oxidative stress in Aspergillus. This work was supported by Austrian Science Foundation Grant FWF-P13202-MOB
2001

abstract No: 

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Full conference title: 

21st Fungal Genetics Conference
    • Fungal Genetics Conference 21st (2000)