Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
Publication DOI: 10.4052/tigg.1504.1EJournal NLM ID: 9425898Correspondence: makotoi
agr.kyushu-u.ac.jp
Institutions: Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Japan
The pathogenic fungus Cryptococcus neoformans causes cryptococcosis, an opportunistic infectious disease resulting in 600,000 deaths per year. The two major glycolipids in C. neoformans are glucosylceramide (GlcCer) with a fungus-specific ceramide (methyl d18 : 2/h18 : 0) and ergosteryl β-glucoside (EG); however, the catabolic pathway of these glycolipids has not yet been uncovered. We found two homologues of endoglycoceramidase (EGCase, EC 3.2.1.123) in C. neoformans, designated Endoglycoceramidase-related Protein 1 and 2 (EGCrP1 and EGCrP2). EGCase hydrolyzes the O-glycosidic linkage between oligosaccharides and ceramides in various glycosphingolipids. However, EGCrP1 and EGCrP2 show completely different specificities; that is, EGCrP1 is a neutral glucocerebrosidase specific to GlcCer, whereas EGCrP2 is an acid β-glucosidase capable of hydrolyzing not only GlcCer but also various β-glucosides, including pNP β-glucoside and EG. Using each disruption mutant of egcrp1 and egcrp2, we elucidated that EGCrP1 plays an integral role in quality control of the fungus-specific GlcCer by eliminating immature GlcCer, which are byproducts of the GlcCer synthesis pathway, whereas EGCrP2 is involved in the catabolism of EG in the vacuoles of C. neoformans. The analysis of egcrp1-disrupted mutants also revealed that the quality control of fungus-specific GlcCer is strongly linked to the formation of the polysaccharide capsule, an important virulence factor. On the other hand, the disruption of EG catabolism resulted in growth arrest, dysfunction in cell budding, and abnormal vacuole morphology. These results indicate that catabolism of two different glycolipids plays different physiological roles in C. neoformans and strongly suggest EGCrP1 and EGCrP2 as targets for anti-cryptococcal drugs with a new mechanism of action
capsule, Cryptococcus neoformans, sterylglucoside, glycolipid catabolism, glucosylceramide quality control, vacuole
Structure type: monomer
C
43H
81O
9N
Location inside paper: Fig. 1, mature GlcCer
Trivial name: cerebroside C, cerebroside D
Compound class: glycolipid, glycosphingolipid, glycoside, cerebroside, ceramide
Contained glycoepitopes: IEDB_137339,IEDB_142488,IEDB_146664,IEDB_983931,SB_192,SB_5
Methods: DNA techniques, TLC, ESI-MS/MS, biological assays, HPLC
Enzymes that release or process the structure: ceramide synthase, fatty acid 2-hydroxylase, sphingolipid Δ-4 desaturase, sphingolipid Δ-8 desaturase, sphingolipid 9-methyltransferase, GCS-1, glucocerebrosidase (EGCrP1)
Related record ID(s): 48267, 48268, 48269, 48271
NCBI Taxonomy refs (TaxIDs): 5207
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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