Tags

Type your tag names separated by a space and hit enter

The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus.
PLoS Genet 2019; 15(9):e1008379PG

Abstract

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.

Authors+Show Affiliations

Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany. Institute of Microbiology, Friedrich Schiller University Jena, Jena, Germany.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany.Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Jena, Germany. Institute of Microbiology, Friedrich Schiller University Jena, Jena, Germany.Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31525190

Citation

Misslinger, Matthias, et al. "The Monothiol Glutaredoxin GrxD Is Essential for Sensing Iron Starvation in Aspergillus Fumigatus." PLoS Genetics, vol. 15, no. 9, 2019, pp. e1008379.
Misslinger M, Scheven MT, Hortschansky P, et al. The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus. PLoS Genet. 2019;15(9):e1008379.
Misslinger, M., Scheven, M. T., Hortschansky, P., López-Berges, M. S., Heiss, K., Beckmann, N., ... Haas, H. (2019). The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus. PLoS Genetics, 15(9), pp. e1008379. doi:10.1371/journal.pgen.1008379.
Misslinger M, et al. The Monothiol Glutaredoxin GrxD Is Essential for Sensing Iron Starvation in Aspergillus Fumigatus. PLoS Genet. 2019;15(9):e1008379. PubMed PMID: 31525190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus. AU - Misslinger,Matthias, AU - Scheven,Mareike Thea, AU - Hortschansky,Peter, AU - López-Berges,Manuel Sánchez, AU - Heiss,Katharina, AU - Beckmann,Nicola, AU - Heigl,Thomas, AU - Hermann,Martin, AU - Krüger,Thomas, AU - Kniemeyer,Olaf, AU - Brakhage,Axel A, AU - Haas,Hubertus, Y1 - 2019/09/16/ PY - 2019/03/04/received PY - 2019/08/20/accepted PY - 2019/09/26/revised PY - 2019/9/17/pubmed PY - 2019/9/17/medline PY - 2019/9/17/entrez SP - e1008379 EP - e1008379 JF - PLoS genetics JO - PLoS Genet. VL - 15 IS - 9 N2 - 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/31525190/The_monothiol_glutaredoxin_GrxD_is_essential_for_sensing_iron_starvation_in_Aspergillus_fumigatus L2 - http://dx.plos.org/10.1371/journal.pgen.1008379 DB - PRIME DP - Unbound Medicine ER -