title: The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus.
abstract: The human pathogenic fungus Aspergillus fumigatus normally lives as a soil saprophyte. Its environment includes poorly oxygenated substrates that also occur during tissue invasive growth of the fungus in the human host. Up to now, few cellular factors have been identified that allow the fungus to efficiently adapt its energy metabolism to hypoxia. Here, we cultivated A. fumigatus in an O2 -controlled fermenter and analysed its responses to O2 limitation on a minute timescale. Transcriptome sequencing revealed several genes displaying a rapid and highly dynamic regulation. One of these genes was analysed in detail and found to encode fungoglobin, a previously uncharacterized member of the sensor globin protein family widely conserved in filamentous fungi. Besides low O2 , iron limitation also induced transcription, but regulation was not entirely dependent on the two major transcription factors involved in adaptation to iron starvation and hypoxia, HapX and SrbA respectively. The protein was identified as a functional haemoglobin, as binding of this cofactor was detected for the recombinant protein. Gene deletion in A. fumigatus confirmed that haem-binding fungoglobins are important for growth in microaerobic environments with O2 levels far lower than in hypoxic human tissue.
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: Falk
authors.initials: F
authors.lastname: Hillmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Linde
authors.forename: Nicola
authors.initials: N
authors.lastname: Beckmann
authors.forename: Michael
authors.initials: M
authors.lastname: Cyrulies
authors.forename: Maria
authors.initials: M
authors.lastname: Strassburger
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heinekamp
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D000222:Adaptation, Physiological; D001232:Aspergillus fumigatus / Q000235:genetics / Q000502:physiology*; D005285:Fermentation; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005914:Globins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D025301:Hyphae / Q000254:growth & development / Q000648:ultrastructure; D007501:Iron / Q000378:metabolism; D009154:Mutation; D010100:Oxygen / Q000502:physiology*; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D005914:Globins; D007501:Iron; D010100:Oxygen