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

PLoS Pathogens

Thierry Fontaine¹  Jean-Paul Latgé¹  Donald C. Sheppard²  Susan G. W. Kaminskyj³  Bridget M. Barker⁴  Arsa Thammahong⁵  Shane R. Baistrocchi⁶  Robert P. Cerone⁶  Fabrice N. Gravelat⁶  Hanna Ostapska⁶  Stefanie D. Baptista⁶  Brendan D. Snarr⁶  Tianli Xiao⁶  Mélanie Lehoux⁶  Benjamin Ralph⁶  Mark J. Lee⁶  Qusai Al Abdallah⁶  Marie-Christine Guiot⁷  Hong Liu⁸  Scott G. Filler⁸  Norma V. Solis⁸  Donald C. Vinh⁹  Christina Gavino⁹ 

[1] Aspergillus Unit, Institut Pasteur, Paris, France;David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America;Department of Biology University of Saskatchewan, Saskatoon, Saskatchewan, Canada;Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America;Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover;Department of Microbiology & Immunology, McGill University, Montreal, Quebec, Canada;Department of Pathology Montreal Neurological Hospital Montreal, Quebec, Canada;Division of Infectious Diseases, LA Biomedical Research Institute at Harbor—UCLA, Torrance, California, United States of America;Infectious Disease Susceptibility Program, McGill University Health Centre, Montreal, Quebec, Canada

关键词: Aspergillus nidulans;    Aspergillus fumigatus;    Neutrophils;    Invasive species;    Virulence factors;    Biofilms;    Fungal diseases;    Cell walls;   

DOI  :  10.1371/journal.ppat.1005187

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY