Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System

Fabrice Gravelat (1) , Anne Beauvais (2) , Hong Liu (3) , Mark Lee (1) , Brendan D. Snarr (1) , Dan Chen (4) , Wenjie Xu (5) , Ilia Kravtsov (1) , Christopher Hoareau (1) , Ghyslaine Vanier (1) , Mirjam Urb (1) , Paolo V. Campoli (1) , Qusai Al Abdallah (1) , Mélanie Lehoux (1) , Josée C. Chabot (1) , Marie-Claude Ouimet (1) , Stefanie D. Baptista (1) , Jörg H Fritz (1) , William C Nierman (4) , Jean Paul Latgé (2) , Aaron P. Mitchell (5) , Scott G Filler (6, 3) , Thierry Fontaine (2) , Donald C. Sheppard (1)

1 McGill University = Université McGill [Montréal, Canada]
2 Aspergillus
3 UCLA - University of California [Los Angeles]
4 J. Craig Venter Institute
5 CMU - Carnegie Mellon University [Pittsburgh]
6 David Geffen School of Medicine [Los Angeles]

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.

Domaines: Mycologie

Fabrice Gravelat, Anne Beauvais, Hong Liu, Mark Lee, Brendan D. Snarr, et al.. Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System. PLoS Pathogens, 2013, 9 (8), pp.e1003575. ⟨10.1371/journal.ppat.1003575⟩. ⟨pasteur-01726798⟩