8 The Cell Wall Polysaccharides of Aspergillus fumigatus

2016 ◽  
pp. 147-165 ◽  
Author(s):  
Mark J. Lee ◽  
Donald C. Sheppard
2014 ◽  
Vol 82 (8) ◽  
pp. 3141-3153 ◽  
Author(s):  
Jagadeesh Bayry ◽  
Audrey Beaussart ◽  
Yves F. Dufrêne ◽  
Meenu Sharma ◽  
Kushagra Bansal ◽  
...  

ABSTRACTInAspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of theA. fumigatusconidial surface.


Author(s):  
Sarah Sze Wah Wong ◽  
Lakshmi Prabha Venugopalan ◽  
Audrey Beaussart ◽  
Anupama Karnam ◽  
Mohammed Razeeth Shait Mohammed ◽  
...  

Although belong to the same genus, Aspergillus fumigatus is primarily involved in invasive pulmonary infection, whereas Aspergillus flavus is a common cause of superficial infection. In this study, we compared conidia (the infective propagules) of these two Aspergillus species. In immunocompetent mice, intranasal inoculation with conidia of A. flavus resulted in significantly higher inflammatory responses in the lungs compared to mice inoculated with A. fumigatus conidia. In vitro assays revealed that the dormant conidia of A. flavus, unlike A. fumigatus dormant conidia, are immunostimulatory. The conidial surface of A. fumigatus was covered by a rodlet-layer, while that of A. flavus were presented with exposed polysaccharides. A. flavus harbored significantly higher number of proteins in its conidial cell wall compared to A. fumigatus conidia. Notably, β-1,3-glucan in the A. flavus conidial cell-wall showed significantly higher percentage of branching compared to that of A. fumigatus. The polysaccharides ensemble of A. flavus conidial cell wall stimulated the secretion of proinflammatory cytokines, and conidial cell wall associated proteins specifically stimulated IL-8 secretion from the host immune cells. Furthermore, the two species exhibited different sensitivities to antifungal drugs targeting cell wall polysaccharides, proposing the efficacy of species-specific treatment strategies. Overall, the species-specific organization of the conidial cell wall could be important in establishing infection by the two Aspergillus species.


2013 ◽  
Vol 289 (3) ◽  
pp. 1243-1256 ◽  
Author(s):  
Mark J. Lee ◽  
Fabrice N. Gravelat ◽  
Robert P. Cerone ◽  
Stefanie D. Baptista ◽  
Paolo V. Campoli ◽  
...  

The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis.


Virulence ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 1870-1879 ◽  
Author(s):  
Kasper Jensen ◽  
Kit P. Lund ◽  
Kimmie B. Christensen ◽  
Anne T. Holm ◽  
Lalit Kumar Dubey ◽  
...  

Immunobiology ◽  
2014 ◽  
Vol 219 (3) ◽  
pp. 179-188 ◽  
Author(s):  
Lalit Kumar Dubey ◽  
Jesper Bonnet Moeller ◽  
Anders Schlosser ◽  
Grith Lykke Sorensen ◽  
Uffe Holmskov

1995 ◽  
Vol 41 (8) ◽  
pp. 714-721 ◽  
Author(s):  
G. Tronchin ◽  
J. P. Bouchara ◽  
M. Ferron ◽  
G. Larcher ◽  
D. Chabasse

Culture conditions that lead to swelling and germination dramatically influence cell surface characteristics and properties of Aspergillus fumigatus conidia. Conidial adherence to polystyrene and agglutination markedly increased during swelling, in a time-dependent manner. Agglutination appeared to be sensitive to cycloheximide and calcium. Removal of cell wall polysaccharides by lyticase or sodium metaperiodate suppressed agglutination of conidia. Proteinase K weakly decreased it whereas dithiothreitol strongly dispersed the cells. These observations suggest that both cell surface carbohydrates and proteins are involved in the agglutination process. Electron microscopic observations demonstrated that the cell wall of conidia was subject to some rearrangements during swelling, involving degradation and loss of the external convoluted layer, and subsequent exposure of underlying ligands. This was confirmed using lectins labelled with gold or fluorescein isothiocyanate, which showed that some carbohydrates, particularly those acting as ligands for peanut agglutinin, are largely exposed during the process. Finally, SDS-PAGE revealed major protein changes between resting and swollen conidia. We conclude that the ability of A. fumigatus conidia to aggregate correlates with an increase in adherence and biochemical reorganization of the cell wall.Key words: Aspergillus fumigatus, adherence, agglutination, cell wall rearrangements.


2009 ◽  
Vol 4 (5) ◽  
pp. 583-595 ◽  
Author(s):  
Amandine Gastebois ◽  
Cécile Clavaud ◽  
Vishukumar Aimanianda ◽  
Jean-Paul Latgé

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sarah Sze Wah Wong ◽  
Vadim B. Krylov ◽  
Dmitry A. Argunov ◽  
Alexander A. Karelin ◽  
Jean-Phillipe Bouchara ◽  
...  

ABSTRACT Methodologies to identify epitopes or ligands of the fungal cell wall polysaccharides influencing the immune response of human pathogens have to date been imperfect. Using the galactomannan (GM) of Aspergillus fumigatus as a model, we have shown that synthetic oligosaccharides of distinct structures representing key fragments of cell wall polysaccharides are the most precise tools to study the serological and immunomodulatory properties of a fungal polysaccharide.


Author(s):  
Haomiao Ouyang ◽  
Yi Zhang ◽  
Hui Zhou ◽  
Yubo Ma ◽  
Ruoyu Li ◽  
...  

Glycosylphosphatidylinositol (GPI)-anchored proteins play important roles in maintaining the function of the cell wall and participating in pathogenic processes. The addition and removal of phosphoethanolamine (EtN-P) on the second mannose residue in the GPI anchor are vital for maturation and sorting of GPI-anchored proteins. Previously, we have shown that deletion of the gpi7, the gene that encodes an EtN-P transferase responsible for the addition of EtN-P to the second mannose residue of the GPI anchor, leads to the mislocalization of GPI-anchored proteins, abnormal polarity, reduced conidiation, and fast germination in Aspergillus fumigatus. In this report, the adherence and virulence of the A. fumigatus gpi7 deletion mutant were further investigated. The germinating conidia of the mutant exhibited an increased adhesion and a higher exposure of cell wall polysaccharides. Although the virulence was not affected, an increased adherence and a stronger inflammation response of the mutant were documented in an immunocompromised mouse model. An in vitro assay confirmed that the Δgpi7 mutant induced a stronger immune response and was more resistant to killing. Our findings, for the first time, demonstrate that in A. fumigatus, GPI anchoring is required for proper organization of the conidial cell wall. The lack of Gpi7 leads to fast germination, stronger immune response, and resistance to macrophage killing.


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