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Taxonomic group: fungi / Basidiomycota (Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11: XN3EH

]

NCBI PubMed ID: 17337638
Publication DOI: 10.1128/EC.00398-06
Journal NLM ID: 101130731
Publisher: American Society for Microbiology
Correspondence: Madhani HD <hiten

biochem.ucsf.edu>
Institutions: Department of Biochemistry and Biophysics and Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA

The principal capsular polysaccharide of the opportunistic fungal pathogen Cryptococcus neoformans consists of an α-1,3-linked mannose backbone decorated with a repeating pattern of glucuronyl and xylosyl side groups. This structure is critical for virulence, yet little is known about how the polymer, called glucuronoxylomannan (GXM), is faithfully synthesized and assembled. We have generated deletions in two genes encoding predicted parallel β-helix repeat proteins, which we have designated PBX1 and PBX2. Deletion of either gene results in a dry-colony morphology, clumpy cells, and decreased capsule integrity. Two-dimensional nuclear magnetic resonance spectroscopy of purified GXM from the mutants indicated that both the wild-type GXM structure and novel, aberrant linkages were present. Carbohydrate composition and linkage analysis determined that these aberrant structures are correlated with the incorporation of terminal glucose residues that are not found in wild-type capsule polysaccharide. We conclude that Pbx1 and Pbx2 are required for the fidelity of GXM synthesis and may be involved in editing incorrectly added glucose residues. PBX1 and PBX2 knockout mutants showed severely attenuated virulence in a murine inhalation model of cryptococcosis. Unlike acapsular strains, these mutant strains induced delayed symptoms of cryptococcosis, though the infected animals eventually contained the infection and recovered.

gene, UDP-Glucose dehydrogenase, Cryptococcus neoformans, glucuronoxylomannan (GXM)

Structure type: polymer chemical repeating unit
Location inside paper: p.631, fig.1A
Compound class: CPS, EPS, glucuronoxylomannan (GXM)
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_1394182,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: 13C NMR, 1H NMR, NMR-2D, virulence assays, PCR, GLC-EI-MS, acid hydrolysis, composition analysis, genetic methods, HPAEC-PAD, microscopy

Related record ID(s): 43555
NCBI Taxonomy refs (TaxIDs): 235443
Reference(s) to other database(s): GTC:G45564VL
Show glycosyltransferases

There are 64 chemically distinct structures. Please, select:

*O[C@H]1[C@H](O)[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@@H]3OC[C@@H](O)[C@H](O)[C@H]3O)[C@@H](O[C@H]3[C@H](O)[C@@H](CO)O[C@H](*)[C@H]3O[C@@H]3OC[C@@H](O)[C@H](O)[C@H]3O)O[C@H](CO)[C@H]2O)[C@H]1O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O

SVG MW SMILES 3D mol Ionize