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Urai M, Kaneko Y, Ueno K, Okubo Y, Aizawa T, Fukazawa H, Sugita T, Ohno H, Shibuya K, Kinjo Y, Miyazaki Y
Evasion of innate immune responses by the highly virulent Cryptococcus gattii by altering capsule glucuronoxylomannan structure
Frontiers in Cellular and Infection Microbiology 5 (2016)
ID 101
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b-D-Xylp-(1-2)-+
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b-D-Xylp-(1-2)-+ |
| |
b-D-GlcpA-(1-2)-+ | |
| | |
-3)-a-D-Manp-(1-3)-a-D-Manp-(1-3)-a-D-Manp-(1- |
Show graphically |
Cryptococcus neoformans H99
(later renamed to: Cryptococcus neoformans var. grubii H99)
(NCBI TaxID 235443,
species name lookup)
Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
The structure was elucidated in this paperNCBI PubMed ID: 26779451Publication DOI: 10.3389/fcimb.2015.00101Journal NLM ID: 101585359Publisher: Lausanne: Frontiers Media SA
Correspondence: Miyazaki Y <ym46
niid.go.jp>
Institutions: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan, Department of Bacteriology, Osaka City University Graduate School of Medicine, Osaka, Japan, Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan, Department of Bioscience in Daily Life, College of Bioresource Sciences, Nihon University, Kanagawa, Japan, Department of Microbiology, Meiji Pharmaceutical University, Tokyo, Japan, Department of Infectious Diseases and Infection Control, Saitama Medical Center, Saitama Medical University, Saitama, Japan
Cryptococcus neoformans causes life-threatening diseases mainly in immunosuppressed hosts such as AIDS patients; C. gattii causes disseminated infections even in healthy hosts. To identify the possible molecular mechanisms underlying this difference in virulence, we investigated the survival and histopathology of lung tissue in wild-type and CD4-depleted mice infected with C. neoformans H99 and C. gattii JP02 (the highly virulent strain isolated in Japan); we then compared dendritic cell (DC) cytokine release responses to different cell fractions from these two strains. JP02-infected mice exhibited shorter survival and fewer inflammatory cells in the lung than H99-infected control mice. Depletion of CD4-related cellular immunity reduced survival of H99-infected mice but had no effect on the survival or inflammatory cell infiltration in JP02-infected mice, suggesting that JP02 evades immune detection. To identify the molecule(s) conferring this difference, we measured cytokine production from murine DCs co-cultured with H99 and JP02 in vitro. The levels of inflammatory cytokines from DCs treated with intact JP02 cells, the extracted capsule, secreted extracellular polysaccharides, and purified glucuronoxylomannan (GXM) were markedly lower than those induced by intact H99 cells and corresponding H99 fractions. Structural analysis of GXM indicated that JP02 altered one of two O-acetyl groups detected in the H99 GXM. Deacetylated GXM lost the ability to induce inflammatory cytokine release from DCs, implicating these O-acetyl groups in immune recognition. We conclude that the highly virulent C. gattii processes a structural alteration in GXM that allows this pathogen to evade the immune response and therefore elimination.
structure, O-acetylation, capsule, dendritic cells, Cryptococcus neoformans, Glucuronoxylomannan, Cryptococcus gattii, innate immune responses
Structure type: structural motif or average structure
Location inside paper: fig. 7A, O-deacetylated GXM H99
Trivial name: glucuronoxylomannan (GXM), glucuronoxylomannan (GXM) Motif M2
Compound class: EPS, CPS, glucuronoxylomannan, cell wall polycaccharide
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: 1H NMR, HPLC, statistical analysis, TFA hydrolysis, O-deacetylation
Synthetic data: chemical
Comments, role: NMR temperature was not specified; O-deacetylated derivative of C. neoformans H99 glucuronoxylomannan
Related record ID(s): 42863
NCBI Taxonomy refs (TaxIDs): 235443Reference(s) to other database(s): GTC:G75580HK
Show glycosyltransferases
NMR conditions: in D2O
1H NMR data: present in publication
|
13C NMR data: present in publication
|
There is only one chemically distinct structure:
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Urai M, Kaneko Y, Ueno K, Okubo Y, Aizawa T, Fukazawa H, Sugita T, Ohno H, Shibuya K, Kinjo Y, Miyazaki Y
Evasion of innate immune responses by the highly virulent Cryptococcus gattii by altering capsule glucuronoxylomannan structure
Frontiers in Cellular and Infection Microbiology 5 (2016)
ID 101
|
b-D-Xylp-(1-2)-+
|
b-D-Xylp-(1-2)-+ |
| |
b-D-GlcpA-(1-2)-+ | |
| | |
-3)-a-D-Manp-(1-3)-a-D-Manp-(1-3)-a-D-Manp-(1-
|
b-D-Xylp-(1-4)-+ |
Show graphically |
Cryptococcus gattii JP02
(later renamed to: Cryptococcus neoformans var. gattii JP02)
(Ancestor NCBI TaxID 37769,
species name lookup)
Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
The structure was elucidated in this paperNCBI PubMed ID: 26779451Publication DOI: 10.3389/fcimb.2015.00101Journal NLM ID: 101585359Publisher: Lausanne: Frontiers Media SA
Correspondence: Miyazaki Y <ym46
niid.go.jp>
Institutions: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan, Department of Bacteriology, Osaka City University Graduate School of Medicine, Osaka, Japan, Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan, Department of Bioscience in Daily Life, College of Bioresource Sciences, Nihon University, Kanagawa, Japan, Department of Microbiology, Meiji Pharmaceutical University, Tokyo, Japan, Department of Infectious Diseases and Infection Control, Saitama Medical Center, Saitama Medical University, Saitama, Japan
Cryptococcus neoformans causes life-threatening diseases mainly in immunosuppressed hosts such as AIDS patients; C. gattii causes disseminated infections even in healthy hosts. To identify the possible molecular mechanisms underlying this difference in virulence, we investigated the survival and histopathology of lung tissue in wild-type and CD4-depleted mice infected with C. neoformans H99 and C. gattii JP02 (the highly virulent strain isolated in Japan); we then compared dendritic cell (DC) cytokine release responses to different cell fractions from these two strains. JP02-infected mice exhibited shorter survival and fewer inflammatory cells in the lung than H99-infected control mice. Depletion of CD4-related cellular immunity reduced survival of H99-infected mice but had no effect on the survival or inflammatory cell infiltration in JP02-infected mice, suggesting that JP02 evades immune detection. To identify the molecule(s) conferring this difference, we measured cytokine production from murine DCs co-cultured with H99 and JP02 in vitro. The levels of inflammatory cytokines from DCs treated with intact JP02 cells, the extracted capsule, secreted extracellular polysaccharides, and purified glucuronoxylomannan (GXM) were markedly lower than those induced by intact H99 cells and corresponding H99 fractions. Structural analysis of GXM indicated that JP02 altered one of two O-acetyl groups detected in the H99 GXM. Deacetylated GXM lost the ability to induce inflammatory cytokine release from DCs, implicating these O-acetyl groups in immune recognition. We conclude that the highly virulent C. gattii processes a structural alteration in GXM that allows this pathogen to evade the immune response and therefore elimination.
structure, O-acetylation, capsule, dendritic cells, Cryptococcus neoformans, Glucuronoxylomannan, Cryptococcus gattii, innate immune responses
Structure type: structural motif or average structure
Location inside paper: fig. 7B, O-deacetylated GXM JP02
Trivial name: glucuronoxylomannan (GXM), glucuronoxylomannan (GXM) Motif M3
Compound class: EPS, CPS, glucuronoxylomannan, cell wall polycaccharide
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: 1H NMR, HPLC, statistical analysis, TFA hydrolysis, O-deacetylation
Synthetic data: chemical
Comments, role: NMR temperature was not specified; O-deacetylated derivative of C. gattii JP02 glucuronoxylomannan
Related record ID(s): 42862, 50825
NCBI Taxonomy refs (TaxIDs): 37769Reference(s) to other database(s): GTC:G42955PN
Show glycosyltransferases
NMR conditions: in D2O
1H NMR data: present in publication
|
13C NMR data: present in publication
|
There is only one chemically distinct structure:
Expand this record
Collapse this record
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