title: Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation.
abstract: Filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. In natural habitats, amoeba predation could impose a major selection pressure towards the acquisition of virulence attributes. To test this hypothesis, we exploited the amoeba Dictyostelium discoideum to study its interaction with Aspergillus fumigatus, two abundant soil inhabitants for which we found co-occurrence in various sites. Fungal conidia were efficiently taken up by D. discoideum, but ingestion was higher when conidia were devoid of the green fungal spore pigment dihydroxynaphtalene melanin, in line with earlier results obtained for immune cells. Conidia were able to survive phagocytic processing, and intracellular germination was initiated only after several hours of co-incubation which eventually led to a lethal disruption of the host cell. Besides phagocytic interactions, both amoeba and fungus secreted cross inhibitory factors which suppressed fungal growth or induced amoeba aggregation with subsequent cell lysis, respectively. On the fungal side, we identified gliotoxin as the major fungal factor killing Dictyostelium, supporting the idea that major virulence attributes, such as escape from phagocytosis and the secretion of mycotoxins are beneficial to escape from environmental predators.
authors: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology.
authors: Falk
authors: F
authors: Hillmann
authors: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology.
authors: Silvia
authors: S
authors: Novohradská
authors: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology.
authors: Derek J
authors: DJ
authors: Mattern
authors: Department of Pharmaceutical Biology, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany.
authors: Tilmann
authors: T
authors: Forberger
authors: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology.
authors: Thorsten
authors: T
authors: Heinekamp
authors: Electron Microscopy Center, Jena University Hospital, Jena, Germany.
authors: Martin
authors: M
authors: Westermann
authors: Department of Pharmaceutical Biology, Institute of Pharmacy, Friedrich Schiller University, Jena, Germany.
authors: Thomas
authors: T
authors: Winckler
authors: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Department of Microbiology and Molecular Biology, Institute of Microbiology.
authors: Axel A
authors: AA
authors: Brakhage
mesh_terms: D000656:Amoeba / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D003510:Cyclohexanes / Q000378:metabolism; D004023:Dictyostelium / Q000382:microbiology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005912:Gliotoxin / Q000378:metabolism*; D006801:Humans; D010587:Phagocytosis; D012717:Sesquiterpenes / Q000378:metabolism; D012987:Soil / Q000469:parasitology*; D013172:Spores, Fungal / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology
chemical_list: D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; D012987:Soil; D037521:Virulence Factors; D005912:Gliotoxin; C026211:fumagillin