title: The mitA gene of Aspergillus fumigatus is required for mannosylation of inositol-phosphorylceramide, but is dispensable for pathogenicity.
abstract: GDP-mannose:inositol-phosphorylceramide (MIPC)-derived glycosphingolipids are important pathogen-associated molecular patterns (PAMP) of Candida albicans and according to recently published data also of Aspergillus fumigatus. MIPC transferases are essential for the synthesis of MIPC, but have so far been studied only in Saccharomyces cerevisiae and C. albicans. Here, we have identified MitA as the only MIPC transferase in A. fumigatus. The DeltamitA mutant lacks MIPC and MIPC-derived glycosphingolipids and accumulates the precursor IPC. The mutant grows normally, shows no defects in cell wall or membrane organization and a normal resistance to different stressors. It is, however, sensitive to high Ca(2+) concentrations, especially during germination. Germination of DeltamitA mutant conidia is also decelerated under normal growth conditions, but neither the virulence of this mutant in a systemic model of infection nor its ability to trigger a cytokine response in macrophages is impaired, arguing against a role of MIPC-derived glycosphingolipids as important A. fumigatus PAMPs.
authors.affiliation: Max-von-Pettenkofer-Institute, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kotz
authors.forename: Johannes
authors.initials: J
authors.lastname: Wagener
authors.forename: Jakob
authors.initials: J
authors.lastname: Engel
authors.forename: Françoise
authors.initials: F
authors.lastname: Routier
authors.forename: Bernd
authors.initials: B
authors.lastname: Echtenacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Petra
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heesemann
authors.forename: Frank
authors.initials: F
authors.lastname: Ebel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006028:Glycosphingolipids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D005656:Fungal Proteins; D006028:Glycosphingolipids; C477937:inositolphosphorylceramide; D008358:Mannose; D002118:Calcium