Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Organ / tissue: capsuleAssociated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
The structure was elucidated in this paperNCBI PubMed ID: 29346417Publication DOI: 10.1371/journal.ppat.1006765Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: Doering TL <doering
wustl.edu>
Institutions: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, USA, School of Biosciences, University of Melbourne, Australia
Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading cause of fungal meningitis worldwide and is responsible for hundreds of thousands of deaths annually. Cryptococcal glycans are required for fungal survival in the host and for pathogenesis. Most glycans are made in the secretory pathway, although the activated precursors for their synthesis, nucleotide sugars, are made primarily in the cytosol. Nucleotide sugar transporters are membrane proteins that solve this topological problem, by exchanging nucleotide sugars for the corresponding nucleoside phosphates. The major virulence factor of C. neoformans is an anti-phagocytic polysaccharide capsule that is displayed on the cell surface; capsule polysaccharides are also shed from the cell and impede the host immune response. Xylose, a neutral monosaccharide that is absent from model yeast, is a significant capsule component. Here we show that Uxt1 and Uxt2 are both transporters specific for the xylose donor, UDP-xylose, although they exhibit distinct subcellular localization, expression patterns, and kinetic parameters. Both proteins also transport the galactofuranose donor, UDP-galactofuranose. We further show that Uxt1 and Uxt2 are required for xylose incorporation into capsule and protein; they are also necessary for C. neoformans to cause disease in mice, although surprisingly not for fungal viability in the context of infection. These findings provide a starting point for deciphering the substrate specificity of an important class of transporters, elucidate a synthetic pathway that may be productively targeted for therapy, and contribute to our understanding of fundamental glycobiology.
virulence, Cryptococcus neoformans, genetic methods, transport proteins
Structure type: structural motif or average structure
Location inside paper: p. 2, Introduction, paragraph 2, GXM
Compound class: O-polysaccharide, glucuronoxylomannan
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_2270799,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: GC-MS, DNA techniques, ELISA, composition analysis, genetic methods, acetylation, dialysis, macrophage activity assay, TEM, centrifugation, ANOVA
Enzymes that release or process the structure: Uxt1, Uxt2
Biosynthesis and genetic data: biochemical data, genetic data
Related record ID(s): 40734, 40735, 40736, 40737, 40738, 48779, 48782
NCBI Taxonomy refs (TaxIDs): 5207Reference(s) to other database(s): GTC:G39597XD
Show glycosyltransferases
There is only one chemically distinct structure:
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