Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C

Haas, Hubertus; Schoeser, Michelle; Lesuisse, Emmanuel; Ernst, Joachim F.; Parson, Walther; Abt, Beate; Winkelmann, G.; Oberegger, Harald

doi:10.1042/bj20021685

Cited by 123 publications

(121 citation statements)

References 61 publications

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“…Generally, 10 g of total RNA was electrophoresed on 1.2% agarose-2.2 M formaldehyde gels and blotted onto Hybond N membranes (Amersham). The hybridization probes used in this study were generated by PCR using oligonucleotides 5Ј-GCACCAGGTCATTGAGTACC-3Ј and 5Ј-TCGTCAGCATGCT CTGGACG-3Ј for sidC (9), 5Ј-GTATATCTTCGCGCAGGG-3Ј and 5Ј-AACC CATCAACACCCGAG-3Ј for mirB (12), and 5Ј-CGGTGATGAGGCACAG T-3Ј and 5Ј-CGGACGTCGACATCAACA-3Ј for ␥-actin-encoding acnA (10).…”

Section: Methodsmentioning

confidence: 99%

“…TAFC ϪFe is a cyclic tripeptide consisting of three N 2 -acetyl-N 5 -cis-anhydromevalonyl-N 5 -hydroxyorhithine residues linked by ester bonds, and FC ϪFe is a cyclic hexapeptide with the structure Gly-Ser-Gly-(N 5 -acetyl-N 5 -hydroxyornithine) 3 (11). After uptake of iron-loaded TAFC ϪFe , termed ferri-triacetylfusarinine C (TAFC ϩFe ), by specific transporters (12), the iron is transferred to metabolic pathways or stored by conversion of FC ϪFe to ferricrocin (FC ϩFe ). TAFC ϪFe is hydrolyzed by an esterase, and the hydrolysis products are excreted (26).…”

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confidence: 99%

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

et al. 2006

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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.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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

et al. 2006

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“…In Ustilago sphaerogena and U. maydis, ferrichrome is taken up as an iron-ligand complex, while iron bound to ferrichrome A is imported via the reductive route (11,83). A. nidulans, which appears to lack a reductive iron assimilatory system (84), possesses three paralogous iron-regulated importers (MirA, MirB, and MirC), of which MirA and MirB are specific for Fe-enterobactin and Fe-TAFC uptake, respectively, while the function of MirC was not yet elucidated (125). Mechanisms of iron release.…”

Section: General Steps Of Siderophore Pathwaysmentioning

confidence: 99%

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,440

1,302

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SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

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“…However, this system would not be efficient unless an iron uptake system were coupled to it. In fact, specific transporters for siderophores have recently been characterized in A. nidulans, which indicates that orthologues probably exist in A. fumigatus (8,14,15). Likewise, even though no system has been described for zinc scavenging to date, a zinc uptake system would be required by pathogens, including A. fumigatus, to incorporate zinc into cells.…”

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The zrfA and zrfB Genes of Aspergillus fumigatus Encode the Zinc Transporter Proteins of a Zinc Uptake System Induced in an Acid, Zinc-Depleted Environment

et al. 2005

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Zinc is an essential micronutrient that cells must obtain from the environment in order to develop their normal growth. Previous work performed at our laboratory showed that the synthesis of immunodominant antigens from Aspergillus spp., including A. fumigatus, was up-regulated by a low environmental concentration of zinc. These results suggested that a tightly regulated system for the fungus to grow under zinc-limiting conditions must underlie the ability of A. fumigatus to acquire zinc in such environments. In this work, we show that zrfA and zrfB are two of the genes that encode membrane zinc transporters from A. fumigatus in this system. Expression of these genes is differentially down-regulated by increasing concentrations of zinc in the medium. Thus, the transcription of zrfB is turned off at a concentration 50-fold higher than that for zrfA transcription. In addition, phenotypic analyses of single zrfA⌬ and zrfB⌬ mutants and a double zrfAzrfB⌬ mutant revealed that the deletion of zrfB causes a greater defect in growth than the single deletion of zrfA. Deletion of both genes has a dramatic effect on growth under acid, zinc-limiting conditions. Interestingly, in neutral or slightly alkaline zinc-depleted medium, the transcriptional expression of both genes is downregulated to such an extent that even in the absence of a supplement of zinc, the expression of zrfA and zrfB is strongly reduced. This fact correlates with the growth observed in alkaline medium, in which even a zrfAzrfB⌬ double mutant was able to grow in a similar way to the wild-type under extremely zinc-limiting conditions. In sum, the zinc transport proteins encoded by zrfA and zrfB are members of a zinc uptake system of A. fumigatus that operates mainly under acid, zinc-limiting conditions.

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Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C

Cited by 123 publications

References 61 publications

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

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

Siderophore-Based Iron Acquisition and Pathogen Control

The zrfA and zrfB Genes of Aspergillus fumigatus Encode the Zinc Transporter Proteins of a Zinc Uptake System Induced in an Acid, Zinc-Depleted Environment

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