title: Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system.
abstract: Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.
authors.affiliation: Departments of Microbiology and Immunology, Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Fabrice N
authors.initials: FN
authors.lastname: Gravelat
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Snarr
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xu
authors.forename: Ilia
authors.initials: I
authors.lastname: Kravtsov
authors.forename: Christopher M Q
authors.initials: CM
authors.lastname: Hoareau
authors.forename: Ghyslaine
authors.initials: G
authors.lastname: Vanier
authors.forename: Mirjam
authors.initials: M
authors.lastname: Urb
authors.forename: Paolo
authors.initials: P
authors.lastname: Campoli
authors.forename: Qusai
authors.initials: Q
authors.lastname: Al Abdallah
authors.forename: Melanie
authors.initials: M
authors.lastname: Lehoux
authors.forename: Josée C
authors.initials: JC
authors.lastname: Chabot
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Ouimet
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Baptista
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Thierry
authors.initials: T
authors.lastname: Fontaine
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D062610:Fungal Polysaccharides / Q000235:genetics / Q000276:immunology*; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D025301:Hyphae / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*; D047071:beta-Glucans / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D002238:Carbohydrate Epimerases; D062610:Fungal Polysaccharides; D005656:Fungal Proteins; D037181:Lectins, C-Type; D011134:Polysaccharides; D037521:Virulence Factors; D047071:beta-Glucans; D000099181:Dectin-1; C062157:galactosaminogalactan