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

What is it about?

FROM THE AUTHOR SUMMARY: 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 (GAG) that is associated with the cell wall of these species. A. fumigatus produces higher amounts of cell wall-associated GAG and is more resistant than A. nidulans to neutrophil killing by NADPH-oxidase dependent extracellular traps (NETs). Increasing cell wall-associated GAG 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.

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Why is it important?

This work allows for development of therapies that could target the protective mechanisms used by A. fumigatus to avoid being killed by DNA NETS and toxins spewed by "self-sacrificing" immune cells. Currently, there are few antifungal drugs that clinicians can used to target invasive infections.

Perspectives