The Intracellular Siderophore Ferricrocin Is Involved in Iron Storage, Oxidative-Stress Resistance, Germination, and Sexual Development in Aspergillus nidulans

Abstract

Iron is required by most organisms, but an excess of this metal is potentially toxic. Consequently, uptake and intracellular storage of iron are tightly controlled. The filamentous fungus A. nidulans lacks the iron storage compound ferritin but possesses an intracellular siderophore, which is accumulated in a highly regulated manner as iron-free desferri-ferricrocin or iron-containing ferricrocin via transcriptional regulation of the nonribosomal peptide synthetase SidC. Biosynthesis of desferri-ferricrocin was low during iron-replete conditions but up-regulated by both iron starvation and intracellular iron excess, the latter caused by either a shift from iron-depleted to high-iron conditions or deregulation of iron uptake. Consequently, ferricrocin constituted only about 5% of the total iron content under iron-replete conditions but up to 64% during conditions of intracellular excess. In contrast, during iron starvation, desferri-ferricrocin was accumulated, which appears to represent a proactive strategy to prevent iron toxicity. Accumulation of the intracellular siderophore was also up-regulated by oxidative stress, which underscores the intertwining of iron metabolism and oxidative stress. Lack of the intracellular siderophore causes pleiotropic effects, as SidC deficiency results in (i) less-efficient utilization of iron, indicated by reduced growth under iron-depleted conditions and a higher iron demand under iron-replete conditions, (ii) delayed germination under iron-depleted conditions, (iii) increased sensitivity of conidia to oxidative stress, and (iv) elimination of cleistothecia formation in homothallic conditions.

Intracellular Siderophores Are Essential for Ascomycete Sexual Development in Heterothallic Cochliobolus heterostrophus and Homothallic Gibberella zeae

“…Asexual spores of an A. nidulans ⌬sidC strain show hypersensitivity to ROS more clearly than mycelia (13). In our experiments, no significant difference in sensitivity to ROS was observed between WT and ⌬nps2 strains of C. heterostrophus during vegetative growth (see Fig.…”

“…Application of ferricrocin fully restored WT fertility to the G. zeae ⌬nps2 strain. Recently, Eisendle et al (13) reported that a ⌬sidC strain is impaired in sexual development in the homothallic ascomycete A. nidulans. Application of ferricrocin restored the ability of the ⌬sidC strain to undergo WT sexual development.…”

“…In contrast, deletion of C. heterostrophus NPS6, which is responsible for extracellular siderophore production, leads to a reduction of asexual sporulation, as well as to a reduction of virulence to the host (23). Recently, intracellular siderophores have been reported also to play a role in the self-compatible sexual development of A. nidulans (13). In addition to siderophores, other small molecules, such as the oxylipin psi factors, have been demonstrated to alter the ratio of asexual to sexual sporulation in A. nidulans (5,6,33) and a small ␥-butyrolactone-containing molecule, butyrolactone I, has been reported as an inducer of asexual sporulation in A. nidulans (27).…”

Dothideomycete–Plant Interactions Illuminated by Genome Sequencing and EST Analysis of the Wheat Pathogen Stagonospora nodorum

“…Three pairs were identified. SNOG_02134.2 was linked to NPS2, and both appear to be orthologous to the Aspergillus nidulans gene SidC (Eisendle et al, 2003), which is responsible for the synthesis of ferricrocin, an intracellular iron storage and transport compound involved in protection against iron toxicity (Eisendle et al, 2006). It is likely that SNOG_02134.2 and NPS2 play similar roles.…”

EstB-Mediated Hydrolysis of the Siderophore Triacetylfusarinine C Optimizes Iron Uptake of Aspergillus fumigatus

“…fumigatus produces two major hydroxamate-type siderophores: the fusarinine desferri-triacetylfusarinine C (DFTafC) is excreted to mobilize extracellular iron, and the ferrichrome desferri-ferricrocin (DF-FC) is employed for intracellular iron storage (4,5,7,16,27). Production of both siderophores is up-regulated by iron starvation, and the A. fumigatus siderophore production resembles that of Aspergillus nidulans (16,27).…”