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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-10-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4619649?pdf=render |
| _version_ | 1818962053900009472 |
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| author | 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 Fontaine Donald C Vinh Scott G Filler Donald C Sheppard |
| author_facet | 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 Fontaine Donald C Vinh Scott G Filler Donald C Sheppard |
| author_sort | Mark J Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T12:23:13Z |
| format | Article |
| id | doaj.art-b6d5e976b224466ca13478d65ff74e9e |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-20T12:23:13Z |
| publishDate | 2015-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b6d5e976b224466ca13478d65ff74e9e2022-12-21T19:40:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-10-011110e100518710.1371/journal.ppat.1005187The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps.Mark J LeeHong LiuBridget M BarkerBrendan D SnarrFabrice N GravelatQusai Al AbdallahChristina GavinoShane R BaistrocchiHanna OstapskaTianli XiaoBenjamin RalphNorma V SolisMélanie LehouxStefanie D BaptistaArsa ThammahongRobert P CeroneSusan G W KaminskyjMarie-Christine GuiotJean-Paul LatgéThierry FontaineDonald C VinhScott G FillerDonald C SheppardOf 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.http://europepmc.org/articles/PMC4619649?pdf=render |
| spellingShingle | 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 Fontaine Donald C Vinh Scott G Filler Donald C Sheppard The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. PLoS Pathogens |
| title | The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. |
| title_full | The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. |
| title_fullStr | The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. |
| title_full_unstemmed | The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. |
| title_short | The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps. |
| title_sort | fungal exopolysaccharide galactosaminogalactan mediates virulence by enhancing resistance to neutrophil extracellular traps |
| url | http://europepmc.org/articles/PMC4619649?pdf=render |
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