The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus

Autoři: Matthias Misslinger aff001;  Mareike Thea Scheven aff002;  Peter Hortschansky aff002;  Manuel Sánchez López-Berges aff001;  Katharina Heiss aff001;  Nicola Beckmann aff001;  Thomas Heigl aff001;  Martin Hermann aff004;  Thomas Krüger aff002;  Olaf Kniemeyer aff002;  Axel A. Brakhage aff002;  Hubertus Haas aff001
Působiště autorů: Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria aff001;  Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll Institute (HKI), Jena, Germany aff002;  Institute of Microbiology, Friedrich Schiller University Jena, Jena, Germany aff003;  Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria aff004
Vyšlo v časopise: The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008379
Kategorie: Research Article


Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for growth; (ii) expression of the encoding gene, grxD, is repressed by the transcription factor SreA in iron replete conditions and upregulated during iron starvation; (iii) during iron starvation but not iron sufficiency, GrxD displays predominant nuclear localization; (iv) downregulation of grxD expression results in de-repression of genes involved in iron-dependent pathways and repression of genes involved in iron acquisition during iron starvation, but did not significantly affect these genes during iron sufficiency; (v) GrxD displays protein-protein interaction with components of the cytosolic iron-sulfur cluster biosynthetic machinery, indicating a role in this process, and with the transcription factors SreA and HapX, which mediate iron regulation of iron acquisition and iron-dependent pathways; (vi) UV-Vis spectra of recombinant HapX or the complex of HapX and GrxD indicate coordination of iron-sulfur clusters; (vii) the cysteine required for iron-sulfur cluster coordination in GrxD is in vitro dispensable for interaction with HapX; and (viii) there is a GrxD-independent mechanism for sensing iron sufficiency by HapX; (ix) inactivation of SreA suppresses the lethal effect caused by GrxD inactivation. Taken together, this study demonstrates that GrxD is crucial for iron homeostasis in A. fumigatus.

Klíčová slova:

Biology and life sciences – Organisms – Eukaryota – Fungi – Fungal molds – Aspergillus – Aspergillus fumigatus – Yeast – Saccharomyces – Saccharomyces cerevisiae – Schizosaccharomyces – Schizosaccharomyces pombe – Microbiology – Medical microbiology – Microbial pathogens – Fungal pathogens – Mycology – Biochemistry – Proteins – DNA-binding proteins – Transcription factors – Regulatory proteins – Amino acids – Sulfur containing amino acids – Cysteine – Protein interactions – Genetics – Gene expression – Gene regulation – Molecular biology – Molecular biology techniques – Molecular biology assays and analysis techniques – Gene expression and vector techniques – Hyperexpression techniques – Medicine and health sciences – Pathology and laboratory medicine – Pathogens – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Carbohydrates – Monosaccharides – Xylose – Organic chemistry – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Yeast and fungal models


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