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


The ubiquitous mold A. fumigatus is isolated in over 80% of all patients with invasive aspergillosis (IA). A. nidulans is a relatively non-pathogenic species that rarely causes IA except in patients with chronic granulomatous disease (CGD), a hereditary disease characterized by impaired neutrophil function due to mutations in the NADPH oxidase complex. Here, we demonstrate that one factor underlying the differences in the intrinsic virulence between A. fumigatus and A. nidulans is the amount of the exopolysaccharide galactosaminogalactan that is associated with the cell wall of these species. A. fumigatus produces higher amounts of cell wall-associated galactosaminogalactan and is more resistant than A. nidulans to neutrophil killing by NADPH-oxidase dependent extracellular traps (NETs). Increasing cell wall-associated galactosaminogalactan in A. nidulans enhanced resistance to NETs and increased the virulence of this species to the same level as A. fumigatus in mice with intact NET formation. Collectively, these data suggest that A. nidulans is more sensitive than A. fumigatus to NADPH-oxidase dependent NETosis due to lower levels of cell wall-associated GAG.


Vyšlo v časopise: The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005187
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005187

Souhrn

The ubiquitous mold A. fumigatus is isolated in over 80% of all patients with invasive aspergillosis (IA). A. nidulans is a relatively non-pathogenic species that rarely causes IA except in patients with chronic granulomatous disease (CGD), a hereditary disease characterized by impaired neutrophil function due to mutations in the NADPH oxidase complex. Here, we demonstrate that one factor underlying the differences in the intrinsic virulence between A. fumigatus and A. nidulans is the amount of the exopolysaccharide galactosaminogalactan that is associated with the cell wall of these species. A. fumigatus produces higher amounts of cell wall-associated galactosaminogalactan and is more resistant than A. nidulans to neutrophil killing by NADPH-oxidase dependent extracellular traps (NETs). Increasing cell wall-associated galactosaminogalactan in A. nidulans enhanced resistance to NETs and increased the virulence of this species to the same level as A. fumigatus in mice with intact NET formation. Collectively, these data suggest that A. nidulans is more sensitive than A. fumigatus to NADPH-oxidase dependent NETosis due to lower levels of cell wall-associated GAG.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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