The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps

Mark J. Lee, Hong Liu, Bridget M. Barker, Brendan D. Snarr, Fabrice N. Gravelat, Qusai Al Abdallah, Christina Gavino, Shane R. Baistrocchi, Hanna Ostapska, Tianli Xiao, Benjamin Ralph, Norma V. Solis, Mélanie Lehoux, Stefanie D. Baptista, Arsa Thammahong, Robert P. Cerone, Susan G.W. Kaminskyj, Marie Christine Guiot, Jean Paul Latgé, Thierry FontaineDonald C. Vinh, Scott G. Filler, Donald C. Sheppard

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Of the over 250 Aspergillus species, Aspergillus fumigatus accounts for up to 80% of invasive human infections. A. fumigatus produces galactosaminogalactan (GAG), an exopolysaccharide composed of galactose and N-acetyl-galactosamine (GalNAc) that mediates adherence and is required for full virulence. Less pathogenic Aspergillus species were found to produce GAG with a lower GalNAc content than A. fumigatus and expressed minimal amounts of cell wall-bound GAG. Increasing the GalNAc content of GAG of the minimally pathogenic A. nidulans, either through overexpression of the A. nidulans epimerase UgeB or by heterologous expression of the A. fumigatus epimerase Uge3 increased the amount of cell wall bound GAG, augmented adherence in vitro and enhanced virulence in corticosteroid-treated mice to levels similar to A. fumigatus. The enhanced virulence of the overexpression strain of A. nidulans was associated with increased resistance to NADPH oxidase-dependent neutrophil extracellular traps (NETs) in vitro, and was not observed in neutropenic mice or mice deficient in NADPH-oxidase that are unable to form NETs. Collectively, these data suggest that cell wall-bound GAG enhances virulence through mediating resistance to NETs.

Original languageEnglish (US)
Article numbere1005187
JournalPLoS Pathogens
Volume11
Issue number10
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

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

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