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Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System

Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gen...

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Autores principales: Gravelat, Fabrice N., Beauvais, Anne, Liu, Hong, Lee, Mark J., Snarr, Brendan D., Chen, Dan, Xu, Wenjie, Kravtsov, Ilia, Hoareau, Christopher M. Q., Vanier, Ghyslaine, Urb, Mirjam, Campoli, Paolo, Al Abdallah, Qusai, Lehoux, Melanie, Chabot, Josée C., Ouimet, Marie-Claude, Baptista, Stefanie D., Fritz, Jörg H., Nierman, William C., Latgé, Jean Paul, Mitchell, Aaron P., Filler, Scott G., Fontaine, Thierry, Sheppard, Donald C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749958/
https://www.ncbi.nlm.nih.gov/pubmed/23990787
http://dx.doi.org/10.1371/journal.ppat.1003575
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author Gravelat, Fabrice N.
Beauvais, Anne
Liu, Hong
Lee, Mark J.
Snarr, Brendan D.
Chen, Dan
Xu, Wenjie
Kravtsov, Ilia
Hoareau, Christopher M. Q.
Vanier, Ghyslaine
Urb, Mirjam
Campoli, Paolo
Al Abdallah, Qusai
Lehoux, Melanie
Chabot, Josée C.
Ouimet, Marie-Claude
Baptista, Stefanie D.
Fritz, Jörg H.
Nierman, William C.
Latgé, Jean Paul
Mitchell, Aaron P.
Filler, Scott G.
Fontaine, Thierry
Sheppard, Donald C.
author_facet Gravelat, Fabrice N.
Beauvais, Anne
Liu, Hong
Lee, Mark J.
Snarr, Brendan D.
Chen, Dan
Xu, Wenjie
Kravtsov, Ilia
Hoareau, Christopher M. Q.
Vanier, Ghyslaine
Urb, Mirjam
Campoli, Paolo
Al Abdallah, Qusai
Lehoux, Melanie
Chabot, Josée C.
Ouimet, Marie-Claude
Baptista, Stefanie D.
Fritz, Jörg H.
Nierman, William C.
Latgé, Jean Paul
Mitchell, Aaron P.
Filler, Scott G.
Fontaine, Thierry
Sheppard, Donald C.
author_sort Gravelat, Fabrice N.
collection PubMed
description Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.
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spelling pubmed-37499582013-08-29 Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System Gravelat, Fabrice N. Beauvais, Anne Liu, Hong Lee, Mark J. Snarr, Brendan D. Chen, Dan Xu, Wenjie Kravtsov, Ilia Hoareau, Christopher M. Q. Vanier, Ghyslaine Urb, Mirjam Campoli, Paolo Al Abdallah, Qusai Lehoux, Melanie Chabot, Josée C. Ouimet, Marie-Claude Baptista, Stefanie D. Fritz, Jörg H. Nierman, William C. Latgé, Jean Paul Mitchell, Aaron P. Filler, Scott G. Fontaine, Thierry Sheppard, Donald C. PLoS Pathog Research Article Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis. Public Library of Science 2013-08-22 /pmc/articles/PMC3749958/ /pubmed/23990787 http://dx.doi.org/10.1371/journal.ppat.1003575 Text en © 2013 Gravelat et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gravelat, Fabrice N.
Beauvais, Anne
Liu, Hong
Lee, Mark J.
Snarr, Brendan D.
Chen, Dan
Xu, Wenjie
Kravtsov, Ilia
Hoareau, Christopher M. Q.
Vanier, Ghyslaine
Urb, Mirjam
Campoli, Paolo
Al Abdallah, Qusai
Lehoux, Melanie
Chabot, Josée C.
Ouimet, Marie-Claude
Baptista, Stefanie D.
Fritz, Jörg H.
Nierman, William C.
Latgé, Jean Paul
Mitchell, Aaron P.
Filler, Scott G.
Fontaine, Thierry
Sheppard, Donald C.
Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title_full Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title_fullStr Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title_full_unstemmed Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title_short Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal β-Glucan from the Immune System
title_sort aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749958/
https://www.ncbi.nlm.nih.gov/pubmed/23990787
http://dx.doi.org/10.1371/journal.ppat.1003575
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