title: HapX Mediates Iron Homeostasis in the Pathogenic Dermatophyte Arthroderma benhamiae but Is Dispensable for Virulence.
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.
authors.affiliation: Junior Research Group Fundamental Molecular Biology of Pathogenic Fungi, 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 (HKI), Jena, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Kröber
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.affiliation: Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shelest
authors.affiliation: Junior Research Group Fundamental Molecular Biology of Pathogenic Fungi, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.|Institute of Microbiology, Friedrich Schiller University, Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.|Institute of Microbiology, Friedrich Schiller University, Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D003883:Arthrodermataceae / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D025301:Hyphae / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007633:Keratins / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D010858:Pigmentation / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D017262:Siderophores / Q000378:metabolism; D013172:Spores, Fungal / Q000187:drug effects / Q000502:physiology; D014774:Virulence / Q000187:drug effects / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D017262:Siderophores; D007633:Keratins; D007501:Iron