The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps.
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.
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Mark J
MJ
Lee
Division of Infectious Diseases, LA Biomedical Research Institute at Harbor-UCLA, Torrance, California, United States of America.
Hong
H
Liu
Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America.
Bridget M
BM
Barker
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Brendan D
BD
Snarr
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Fabrice N
FN
Gravelat
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Qusai
Q
Al Abdallah
Infectious Disease Susceptibility Program, McGill University Health Centre, Montreal, Quebec, Canada.
Christina
C
Gavino
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Shane R
SR
Baistrocchi
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Hanna
H
Ostapska
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Tianli
T
Xiao
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Benjamin
B
Ralph
Division of Infectious Diseases, LA Biomedical Research Institute at Harbor-UCLA, Torrance, California, United States of America.
Norma V
NV
Solis
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Mélanie
M
Lehoux
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Stefanie D
SD
Baptista
Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover.
Arsa
A
Thammahong
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada.
Robert P
RP
Cerone
Department of Biology University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Susan G W
SG
Kaminskyj
Department of Pathology Montreal Neurological Hospital Montreal, Quebec, Canada.
Marie-Christine
MC
Guiot
Aspergillus Unit, Institut Pasteur, Paris, France.
Jean-Paul
JP
Latgé
Aspergillus Unit, Institut Pasteur, Paris, France.
Thierry
T
Fontaine
Infectious Disease Susceptibility Program, McGill University Health Centre, Montreal, Quebec, Canada.
Donald C
DC
Vinh
Division of Infectious Diseases, LA Biomedical Research Institute at Harbor-UCLA, Torrance, California, United States of America; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
Scott G
SG
Filler
Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
Donald C
DC
Sheppard
D000818:Animals; D001230:Aspergillus / Q000472:pathogenicity*; D018441:Biofilms; D065206:Extracellular Traps; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D011134:Polysaccharides / Q000502:physiology*; D014774:Virulence
D011134:Polysaccharides; C062157:galactosaminogalactan