Journal article
Cryptococcal Xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans Plays a Direct Role in the Synthesis of Capsule Polysaccharides
The Journal of biological chemistry, Vol.283(21), pp.14327-14334
05/23/2008
DOI: 10.1074/jbc.M708927200
PMCID: PMC2386922
PMID: 18347023
Abstract
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.
Details
- Title: Subtitle
- Cryptococcal Xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans Plays a Direct Role in the Synthesis of Capsule Polysaccharides
- Creators
- J. Stacey Klutts - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110Tamara L Doering - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.283(21), pp.14327-14334
- Publisher
- Elsevier Inc
- DOI
- 10.1074/jbc.M708927200
- PMID
- 18347023
- PMCID
- PMC2386922
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Grant note
- Grants GM R01 071007 / National Institutes of Health
- Language
- English
- Date published
- 05/23/2008
- Academic Unit
- Pathology
- Record Identifier
- 9984046833402771
Metrics
7 Record Views