The Role of Ornithine Supply in Siderophore Biosynthesis in Aspergillus fumigatus

Ref ID: 18470

Author:

Lukas Schafferer, Nicola Beckmann, Hubertus Haas

Author address:

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

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Background: Iron is an essential nutrient required for a wide range of cellular processes. However, excessive iron
accumulation is toxic. Therefore, microorganisms evolved fine8208;tuned iron uptake and storage mechanisms, such as
the siderophore system. The opportunistic fungal pathogen Aspergillus fumigatus produces siderophores (lowmolecular
mass iron8208;specific chelators) to acquire, store and distribute iron. Past studies indicated coordination of
siderophore biosynthesis with supply of its precursor ornithine.
Methods: The role of mitochondrial ornithine production in siderophore biosynthesis of A. fumigatus was
characterized by analysis of the phenotypic consequences of genetic inactivation of the putative mitochondrial
ornithine exporter, AmcA (Afu_8g02760).
Results: Consistent with a role in mitochondrial ornithine export, inactivation of AmcA resulted in a decrease in the
cellular ornithine content as well as a decrease in extra8208; and intracellular siderophore production. In the presence
of the iron chelator bathophenanthroline disulfonate, which inhibits siderophore8208;independent iron uptake, AmcAdeficiency
decreased conidiation, indicating increased iron starvation. In contrast to siderophore production,
AmcA8208;deficiency didn’t affect the cellular content in polyamines, which are also derived from ornithine via the
ornithine decarboxylase. Nevertheless, AmcA8208;deficiency increased the susceptibility of A. fumigatus to
eflornithine, an inhibitor of the ornithine decarboxylase, most likely due to the decreased ornithine pool.
Conclusion: Siderophore biosynthesis is mainly fueled by mitochondrial production of ornithine, rather than by
conversion of arginine to ornithine in the cytoplasm. There exists coordination between siderophore biosynthesis
and its precursor supply. This study also indicates a prioritization of ornithine flux into synthesis of polyamines
compared to siderophores, emphasizing the essentiality of polyamines.

Abstract Number: PR1.62

Conference Year: 2012

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

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