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

Fabrice N. Gravelat, Anne Beauvais, Hong Liu, Mark J. Lee, Brendan D. Snarr, Dan Chen, Wenjie Xu, Ilia Kravtsov, Christopher M.Q. Hoareau, Ghyslaine Vanier, Mirjam Urb, Paolo Campoli, Qusai Al Abdallah, Melanie Lehoux, Josée C. Chabot, Marie Claude Ouimet, Stefanie D. Baptista, Jörg H. Fritz, William C. Nierman, Jean Paul Latgé & 4 others Aaron P. Mitchell, Scott G. Filler, Thierry Fontaine, Donald C. Sheppard

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere1003575
JournalPLoS Pathogens
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Glucans
Aspergillus
Immune System
Aspergillus fumigatus
Aspergillosis
Fungi
Racemases and Epimerases
Virulence Factors
Fibronectins
Adhesives
Cell Wall
Plastics
Virulence
Epithelial Cells
galactosaminogalactan
Genes

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Gravelat, F. N., Beauvais, A., Liu, H., Lee, M. J., Snarr, B. D., Chen, D., ... Sheppard, D. C. (2013). Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System. PLoS Pathogens, 9(8), [e1003575]. https://doi.org/10.1371/journal.ppat.1003575

Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System. / Gravelat, Fabrice N.; Beauvais, Anne; Liu, Hong; Lee, Mark J.; Snarr, Brendan D.; Chen, Dan; Xu, Wenjie; Kravtsov, Ilia; Hoareau, Christopher M.Q.; Vanier, Ghyslaine; Urb, Mirjam; Campoli, Paolo; Al Abdallah, Qusai; Lehoux, Melanie; Chabot, Josée C.; Ouimet, Marie Claude; Baptista, Stefanie D.; Fritz, Jörg H.; Nierman, William C.; Latgé, Jean Paul; Mitchell, Aaron P.; Filler, Scott G.; Fontaine, Thierry; Sheppard, Donald C.

In: PLoS Pathogens, Vol. 9, No. 8, e1003575, 01.08.2013.

Research output: Contribution to journalArticle

Gravelat, FN, Beauvais, A, Liu, H, Lee, MJ, Snarr, BD, Chen, D, Xu, W, Kravtsov, I, Hoareau, CMQ, Vanier, G, Urb, M, Campoli, P, Al Abdallah, Q, Lehoux, M, Chabot, JC, Ouimet, MC, Baptista, SD, Fritz, JH, Nierman, WC, Latgé, JP, Mitchell, AP, Filler, SG, Fontaine, T & Sheppard, DC 2013, 'Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System', PLoS Pathogens, vol. 9, no. 8, e1003575. https://doi.org/10.1371/journal.ppat.1003575
Gravelat, Fabrice N. ; Beauvais, Anne ; Liu, Hong ; Lee, Mark J. ; Snarr, Brendan D. ; Chen, Dan ; Xu, Wenjie ; Kravtsov, Ilia ; Hoareau, Christopher M.Q. ; Vanier, Ghyslaine ; Urb, Mirjam ; Campoli, Paolo ; Al Abdallah, Qusai ; Lehoux, Melanie ; Chabot, Josée C. ; Ouimet, Marie Claude ; Baptista, Stefanie D. ; Fritz, Jörg H. ; Nierman, William C. ; Latgé, Jean Paul ; Mitchell, Aaron P. ; Filler, Scott G. ; Fontaine, Thierry ; Sheppard, Donald C. / Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System. In: PLoS Pathogens. 2013 ; Vol. 9, No. 8.
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