earticle

영어

The encapsulated basidiomycetous Cryptococcus neoformans species complex is an opportunistic fungal pathogen causing fatal cryptococcal meningoencephalitis in immunocompromised populations, such as AIDS patients. In this presentation, we report the unique structure and biosynthesis pathway of N-/O-glycans and their physiological roles in C. neoformans. By analyzing oligosaccharide profiles combined with exoglycosidase treatment, C. neoformans was shown to have serotype-specific high-mannose type N-glycans with or without xylose residue. Moreover, comparative analysis of acidic N-glycan profiles from wild-type and och1Δ, mnn2Δ, and uxs1Δ mutant strains strongly indicated the presence of xylose-phosphates attached to mannose residues in the core form and outer chain of N-glycans (1). We further showed that the major C. neoformans O-glycans were short manno-oligosaccharides that were connected mostly by α1,2-linkages but connected by an α 1,6-linkage at the third mannose residue. C. neoformans KTR3 was shown to be responsible for the addition of the second α1,2 mannose residue to the major O-glycans lacking xylose. The ktr3Δ mutant strain displayed attenuated virulence in a mouse model of cryptococcosis, suggesting that the extended structure of O-glycans is required for full pathogenicity of C. neoformans. Intriguingly, C. neoformans HOC1 and HOC3, homologs of the Saccharomyces cerevisiae OCH1 family genes, were shown to transfer the third mannose residue, via an α1,6 linkage, to minor O-glycans containing xylose and to major O-glycans without xylose, respectively, indicating two independent O-glycan biosynthesis pathways involving different sets of processing enzymes in C. neoformans (2). The glycosylation-defective mutant strains developed in our study are currently used for systematic investigation on how structural alterations of N-/O-glycans affect the intensity of virulence and the extent of host immunological interactions in C. neoformans.