title: Surface structure characterization of Aspergillus fumigatus conidia mutated in the melanin synthesis pathway and their human cellular immune response.
abstract: In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, Université Paris Descartes, Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.affiliation: Université Catholique de Louvain, Institute of Life Sciences, Louvain-la-Neuve, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Beaussart
authors.affiliation: Université Catholique de Louvain, Institute of Life Sciences, Louvain-la-Neuve, Belgium.
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, Université Paris Descartes, Paris, France.
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, Université Paris Descartes, Paris, France.
authors.forename: Kushagra
authors.initials: K
authors.lastname: Bansal
authors.affiliation: Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology, University of Jena, Jena, Germany Integrated Research and Treatment Center, Center for Sepsis Control and Care Jena, University Hospital, Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.affiliation: Unité des Aspergillus, Institut Pasteur, Paris, France.
authors.forename: Vishukumar
authors.initials: V
authors.lastname: Aimanianda
authors.affiliation: Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology, University of Jena, Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, Université Paris Descartes, Paris, France.
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Kwon-Chung
authors.affiliation: Unité des Aspergillus, Institut Pasteur, Paris, France jean-paul.latge@pasteur.fr anne.beauvais@pasteur.fr.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.affiliation: Unité des Aspergillus, Institut Pasteur, Paris, France jean-paul.latge@pasteur.fr anne.beauvais@pasteur.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
mesh_terms: D001232:Aspergillus fumigatus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D053898:Biosynthetic Pathways / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D017353:Gene Deletion; D006801:Humans; D007111:Immunity, Cellular; D008543:Melanins / Q000096:biosynthesis*; D013172:Spores, Fungal / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D013499:Surface Properties
chemical_list: D016207:Cytokines; D008543:Melanins