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PLoS One. 2016 Mar 9;11(3):e0150701. doi: 10.1371/journal.pone.0150701. eCollection 2016.

HapX Mediates Iron Homeostasis in the Pathogenic Dermatophyte Arthroderma benhamiae but Is Dispensable for Virulence.

Author information

1
Junior Research Group Fundamental Molecular Biology of Pathogenic Fungi, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany.
2
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
3
Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
4
Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
5
Institute of Microbiology, Friedrich Schiller University, Jena, Germany.

Abstract

For many pathogenic fungi, siderophore-mediated iron acquisition is essential for virulence. The process of siderophore production and further mechanisms to adapt to iron limitation are strictly controlled in fungi to maintain iron homeostasis. Here we demonstrate that the human pathogenic dermatophyte Arthroderma benhamiae produces the hydroxamate siderophores ferricrocin and ferrichrome C. Additionally, we show that the iron regulator HapX is crucial for the adaptation to iron starvation and iron excess, but is dispensable for virulence of A. benhamiae. Deletion of hapX caused downregulation of siderophore biosynthesis genes leading to a decreased production of siderophores during iron starvation. Furthermore, HapX was required for transcriptional repression of genes involved in iron-dependent pathways during iron-depleted conditions. Additionally, the ΔhapX mutant of A. benhamiae was sensitive to high-iron concentrations indicating that HapX also contributes to iron detoxification. In contrast to other pathogenic fungi, HapX of A. benhamiae was redundant for virulence and a ΔhapX mutant was still able to infect keratinized host tissues in vitro. Our findings underline the highly conserved role of the transcription factor HapX for maintaining iron homeostasis in ascomycetous fungi but, unlike in many other human and plant pathogenic fungi, HapX of A. benhamiae is not a virulence determinant.

PMID:
26960149
PMCID:
PMC4784894
DOI:
10.1371/journal.pone.0150701
[Indexed for MEDLINE]
Free PMC Article

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