Iron is an essential nutrient required for a wide range of cellular processes. However, excessive iron accumulation is toxic. Therefore, microorganisms evolved fine-tuned iron uptake and storage mechanisms, such as the siderophore system. The opportunistic fungal pathogen Aspergillus fumigatus produces siderophores to acquire, store and distribute iron. Past studies indicated coordination of siderophore biosynthesis with supply of its precursor ornithine. 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). 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 extra- and intracellular siderophore production. In the presence of the iron chelator bathophenanthroline disulfonate, which inhibits siderophore- independent iron uptake, AmcAdeficiency decreased conidiation, indicating increased iron starvation. In contrast to siderophore production, AmcA- deficiency didn't affect the cellular content in polyamines, which are also derived from ornithine via the ornithine decarboxylase. Nevertheless, AmcAdeficiency increased the susceptibility of A. fumigatus to eflornithine, an inhibitor of the ornithine decarboxylase, most likely due to the decreased ornithine pool. 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.
Full conference title:
- Asperfest 9 (2012)