Search

In contrast to obligate pathogens opportunistic pathogens such as Aspergillus fumigatus do not need a specific host to propagate or survive. However several characteristics of the saprophytic life-style and the selective pressure encountered in the primary ecological niche contribute to the virulence of A. fumigatus. All fungi depend on metals for growth and proliferation, like iron, copper, zinc, manganese or calcium. In the recent past several studies explored the manifold impact of metals modulating virulence of pathogens. Components which might be scarce in the natural environment but also in the host due to nutritional immunity. This review recapitulates molecular constituents of metal ion uptake systems in A. fumigatus, their regulation and their significance at the host-pathogen battlefield., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The filamentous fungus Acremonium chrysogenum is of enormous biotechnological importance as it represents the natural producer of the beta-lactam antibiotic cephalosporin C. However, a limitation in genetic tools, e.g. promoters for conditional gene expression, impedes genetic engineering of this fungus. Here we demonstrate that in A. chrysogenum iron starvation induces the production of the extracellular siderophores dimerumic acid, coprogen B, 2-N-methylcoprogen B and dimethylcoprogen as well as expression of the putative siderophore transporter gene, mir1. Moreover, we show that the promoter of mir1, mir1(P), is suitable for conditional expression of target genes in A. chrysogenum as shown by mir1(P)-driven and iron starvation-induced expression of genes encoding green fluorescence protein and phleomycin resistance. The obtained iron-starvation dependent phleomycin resistance indicates the potential use of this promoter for selection marker recycling. Together with easy scorable siderophore production, the co-regulation of mir1 expression and siderophore production facilitates the optimization of the inducing conditions of this expression system., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed phenotypes is not clear. Here, we report that A. fumigatus SREBP, SrbA, mediates regulation of iron acquisition in response to hypoxia and low iron conditions. To further define SrbA's role in iron acquisition in relation to previously studied fungal regulators of iron metabolism, SreA and HapX, a series of mutants were generated in the ΔsrbA background. These data suggest that SrbA is activated independently of SreA and HapX in response to iron limitation, but that HapX mRNA induction is partially dependent on SrbA. Intriguingly, exogenous addition of high iron or genetic deletion of sreA in the ΔsrbA background was able to partially rescue the hypoxia growth, triazole drug susceptibility, and decrease in ergosterol content phenotypes of ΔsrbA. Thus, we conclude that the fungal SREBP, SrbA, is critical for coordinating genes involved in iron acquisition and ergosterol biosynthesis under hypoxia and low iron conditions found at sites of human fungal infections. These results support a role for SREBP-mediated iron regulation in fungal virulence, and they lay a foundation for further exploration of SREBP's role in iron homeostasis in other eukaryotes., Competing Interests: The authors have declared that no competing interests exist.

Aspergillus fumigatus employs two high affinity iron uptake mechanisms, siderophore mediated iron uptake and reductive iron assimilation (RIA). The A. fumigatus genome encodes 15 putative metalloreductases (MR) but the ferrireductases involved in RIA remained elusive so far. Expression of the MR FreB was found to be transcriptionally repressed by iron via SreA, a repressor of iron acquisition during iron sufficiency, indicating a role in iron metabolism. FreB-inactivation by gene deletion was phenotypically largely inconspicuous unless combined with inactivation of the siderophore system, which then decreased growth rate, surface ferrireductase activity and oxidative stress resistance during iron starvation. This study also revealed that loss of copper-independent siderophore-mediated iron uptake increases sensitivity of A. fumigatus to copper starvation due to copper-dependence of RIA., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Iron is an essential metal for virtually all organisms. Iron acquisition is well characterized for various organisms, whereas intracellular iron distribution is poorly understood. In contrast to bacteria, plants, and animals, most fungi lack ferritin-mediated iron storage but possess an intracellular siderophore shown to be involved in iron storage. Here we demonstrate that deficiency in the intracellular siderophore ferricrocin causes iron starvation in conidia of Aspergillus fumigatus, demonstrating that ferricrocin is also involved in intra- and transcellular iron distribution. Thus, ferricrocin represents the first intracellular iron transporter identified in any organism.