Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Organ / tissue: cell wallAssociated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
NCBI PubMed ID: 18347023Publication DOI: 10.1074/jbc.M708927200Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: doering
wustl.edu
Institutions: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, USA, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA, Campus Box 8230, St. Louis, USA
The opportunistic yeast Cryptococcus neoformans causes serious disease in humans and expresses a prominent polysaccharide capsule that is required for its virulence. Little is known about how this capsule is synthesized. We previously identified a β1,2-xylosyltransferase (Cxt1p) with in vitro enzymatic activity appropriate for involvement in capsule synthesis. Here, we investigate C. neoformans strains in which the corresponding gene has been deleted (cxt1Δ). Loss of CXT1 does not affect in vitro growth of the mutant cells or the general morphology of their capsules. However, NMR structural analysis of the two main capsule polysaccharides, glucuronoxylomannan (GXM) and galactoxylomannan (GalXM), showed that both were missing β1,2-xylose residues. There was an ~30% reduction in the abundance of this residue in GXM in mutant compared with wild-type strains, and mutant GalXM was almost completely devoid of β1,2-linked xylose. The GalXM from the mutant strain was also missing a β1,3-linked xylose residue. Furthermore, deletion of CXT1 led to attenuation of cryptococcal growth in a mouse model of infection, suggesting that the affected xylose residues are important for normal host-pathogen interactions. Cxt1p is the first glycosyltransferase with a defined role in C. neoformans capsule biosynthesis, and cxt1Δ is the only strain identified to date with structural alterations of the capsule polysaccharide GalXM.
capsular polysaccharides, Xylose, Cryptococcus neoformans, cryptococcosis, gene deletion
Structure type: structural motif or average structure
Location inside paper: Fig.5, right
Compound class: glycoinositolphosphoryl ceramide (GIPC)
Contained glycoepitopes: IEDB_114701,IEDB_130701,IEDB_136906,IEDB_137472,IEDB_140116,IEDB_141793,IEDB_141794,IEDB_144983,IEDB_145668,IEDB_151528,IEDB_152206,IEDB_153220,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_190606,IEDB_983930,SB_197,SB_198,SB_44,SB_67,SB_7,SB_72
Methods: 13C NMR, 1H NMR, methylation, NMR-2D, GC-MS, acid hydrolysis, biological assays, Southern blotting, extraction, acetylation, reduction, cell growth, precipitation, immunofluorescence
Related record ID(s): 44020, 44530
NCBI Taxonomy refs (TaxIDs): 40410
Show glycosyltransferases
There is only one chemically distinct structure:
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(later renamed to: Cryptococcus neoformans var. neoformans)