Definitive chemical evidence for the constitutive ability of <i>Candida albicans</i> serotype A strains to synthesize β‐1,2 linked oligomannosides containing up to 14 mannose residues

Trinel, Pierre-André; Lepage, Gilbert; Jouault, Thierry; Strecker, G; Poulain, Daniel

doi:10.1016/s0014-5793(97)01205-2

Cited by 31 publications

(32 citation statements)

References 36 publications

(51 reference statements)

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“…The stimulating activity of ␤-1,2- oligomannosides was found to depend on the length of the mannosyl chain and maximum activity was observed for DPs of 8 or higher (13). Interestingly, these high DPs are present mainly in the C. albicans PLM but correspond to minor components among the ␤-1,2-oligomannosides released from the mannan of the same species (24).…”

Section: Discussionmentioning

confidence: 95%

“…7 we suggest a structural model for the PLM glycan moiety, based on the first chemical evidence for the presence of ␤-1,2-linked oligomannosides in a glycoconjugate other than the yeast phosphopeptidomannan. Very little is known about ␤-1,2-mannosyltransferases of C. albicans, their activation and substrate specificity, but the presence of such linear chains of up to 18 mannose residues represent quite unusual structures (24). It has been suggested that a consequence of coating parasite surfaces with long sugar chains is the triggering of host effector mechanisms at a distance too great for efficient antimicrobial activity on the parasite.…”

Section: Discussionmentioning

confidence: 99%

“…Dg) generated by alkaline hydrolysis of [ 3 H] inositol-labeled or unlabeled PLM was analyzed on aluminum-backed silica gel 60 TLC plates developed in butanol/acetic acid/water (20:8:17, by volume). ␤-1,2-Linked oligomannosides (DP 13 and 14) prepared from the phosphopeptidomannan of the same C. albicans strain (24) were used as controls. Plates were then analyzed by either fluorography or orcinol staining.…”

Section: Strainmentioning

confidence: 99%

“…(Isotopchim). The purification of high amounts of PLM for physicochemical analysis was performed from yeast cells grown at 28°C in a bioreactor as described for the preparation of phosphopeptidomannan (24).…”

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confidence: 99%

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The Candida albicans Phospholipomannan Is a Family of Glycolipids Presenting Phosphoinositolmannosides with Long Linear Chains of β-1,2-Linked Mannose Residues

Trinel

Plancke

Gerold

et al. 1999

Journal of Biological Chemistry

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In a series of studies, we have shown that Candida albicans synthesizes a glycolipid, phospholipomannan (PLM), which reacted with antibodies specific for ␤-1,2-oligomannosides and was biosynthetically labeled by [ 3 H]mannose, [3 H]palmitic acid, and [ 32 P]phosphorus. PLM has also been shown to be released from the C. albicans cell wall and to bind to and stimulate macrophage cells. In this study, we show by thin layer chromatography scanning of metabolically radiolabeled extracts that the C. albicans PLM corresponds to a family of mannose and inositol co-labeled glycolipids. We describe the purification process of the molecule and the release of its glycan fraction through alkaline hydrolysis. Analysis of this glycan fraction by radiolabeling and methylation-methanolysis confirmed the presence of inositol and of 1,2-linked mannose units. NMR studies evidenced linear chains of ␤-1,2-oligomannose as the major PLM components. Mass spectrometry analysis revealed that these chains were present in phosphoinositolmannosides with degrees of polymerization varying from 8 to 18 sugar residues. The PLM appears as a new type of eukaryotic inositol-tagged glycolipid in relationship to both the absence of glucosamine and the organization of its glycan chains. This first structural evidence for the presence of ␤-1,2-oligomannosides in a glycoconjugate other than the C. albicans phosphopeptidomannan may have some pathophysiological relevance to the adhesive, protective epitope, and signaling properties thus far established for these residues.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Strainmentioning

confidence: 99%

mentioning

confidence: 99%

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The Candida albicans Phospholipomannan Is a Family of Glycolipids Presenting Phosphoinositolmannosides with Long Linear Chains of β-1,2-Linked Mannose Residues

Trinel

Plancke

Gerold

et al. 1999

Journal of Biological Chemistry

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“…These side chains in C. albicans consist of ␣1,2-and ␣1,3-linked mannose residues (20 -22) and in serotype A strains ␤1,2-linked mannose residues (23). The side chains and positions within the core are also modified by the addition of phosphomannan, consisting of a chain of ␤1,2-linked mannose residues attached via a phosphodiester bond (24). Previous studies in C. albicans have demonstrated the overall importance of glycosylation for cellular viability and virulence (25)(26)(27).…”

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confidence: 99%

Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans

Bates

Hughes

Munro

et al. 2006

Journal of Biological Chemistry

217

277

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The outer layer of the Candida albicans cell wall is enriched in highly glycosylated mannoproteins that are the immediate point of contact with the host and strongly influence the host-fungal interaction. N-Glycans are the major form of mannoprotein modification and consist of a core structure, common to all eukaryotes, that is further elaborated in the Golgi to form the highly branched outer chain that is characteristic of fungi. In yeasts, outer chain branching is initiated by the action of the ␣1,6-mannosyltransferase Och1p; therefore, we disrupted the C. albicans OCH1 homolog to determine the importance of outer chain N-glycans on the host-fungal interaction. Loss of CaOCH1 resulted in a temperature-sensitive growth defect and cellular aggregation. Outer chain elongation of N-glycans was absent in the null mutant, demonstrated by the lack of the ␣1,6-linked polymannose backbone and the underglycosylation of N-acetylglucosaminidase. A null mutant lacking OCH1 was hypersensitive to a range of cell wall perturbing agents and had a constitutively activated cell wall integrity pathway. These mutants had near normal growth rates in vitro but were attenuated in virulence in a murine model of systemic infection. However, tissue burdens for the Caoch1⌬ null mutant were similar to control strains with normal N-glycosylation, suggesting the host-fungal interaction was altered such that high burdens were tolerated. This demonstrates the importance of N-glycan outer chain epitopes to the host-fungal interaction and virulence.Candida albicans is a commensal organism carried by a significant proportion of healthy individuals. It is the most common opportunistic fungal pathogen of humans causing superficial infections of the mucosa and in the immunocompromised host life-threatening systemic infections (1-4). The cell wall is the immediate point of contact between fungus and host and plays an important role in adherence, antigenicity, and the modulation of the host immune response (5-9). The outer layer of the cell wall is enriched in highly glycosylated mannoproteins (10), and both the protein and carbohydrate components have been implicated in the host-fungal interaction (5, 6, 11). The study of glycosylation in C. albicans therefore has its own relevance in identifying the carbohydrate epitopes involved in pathogenesis.Cell surface mannoproteins contain both O-and N-linked oligosaccharides. The O-linked oligosaccharides, attached to serine or threonine, consist of a linear chain of one to five ␣1,2-linked mannose residues (12)(13)(14) and are known to be required for full virulence (14). The process of N-glycosylation has been studied extensively in Saccharomyces cerevisiae. N-Linked glycosylation is initiated in the endoplasmic reticulum with the transfer of the Glc 3 Man 9 GlcNAc 2 oligosaccharide precursor to the protein target (15, 16). The oligosaccharide precursor is then processed by endoplasmic reticulum-resident glucosidases and a mannosidase to yield the mature triantennary Man 8 GlcNAc 2 core (17). Outer chain ...

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Stereoselective Synthesis of β‐Mannosides

Pozsgay¹

2000

Carbohydrates in Chemistry and Biology

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IntroductionP-D-Mannopyranosyl residues are frequently found in oligosaccharides and glycoconjugates in living systems. This unit is omnipresent in N-linked glycoproteins that contain a pentasaccharide core (1) in which the P-linked mannose residue can carry additional sugars [I] (Scheme 1). P-Mannopyranose moieties are often part of the 0-specific polysaccharides (OSPs) of Gram-negative bacteria [2-8] and of bacterial capsular and em-polysaccharides [6,[9][10][11][12][13][14][15]. P-Linked mannopyranose is also a common residue in plant polysaccharides [ 161. Further examples of the occurrence of the P-mannosidic linkage are the glycosphingolipids in wheat flour [ 171 and in the freshwater bivalve Hyriopsis schlegelii [ 181. Interestingly, this residue is absent from mammalian glycolipids [19]. Cell-wall phosphomannans of yeasts contain linear chains of up to fourteen P-1,2-linked mannose residues [20, 211. P-Mannopyranose units also occur in secreted small molecules. Examples include the phospholipase inhibitor caloporoside [22] and free oligosaccharides detected in a patient with mannosidosis [23] and isolated from ripening tomatoes [24]. The related P-linked 2-acetamido-2deoxy-D-mannopyranose also frequently occurs in OSPs [ 8, 251 and in capsular polysaccharides [26-3 11. The corresponding mannuronic acid is present in the enterobacterial common antigen [32] and in other bacterial polysaccharides [6, 331.The occurrence of the 0-mannosyl unit in many biological systems creates a biological rationale for its synthesis. Whereas the simple methyl [34-381 and phenyl P-D-mannopyranoside [ 391 have been known for many years, the synthesis of complex oligosaccharides containing this unit is still a challenge for two reasons [40-441. First, the anomeric effect facilitates the formation of the 1,2-truns-mannopyranosyl (a) linkage thus it disfavors the P-linkage and, second, the 1,2-cis arrangement of the equatorial aglycone and the axial functionality at C-2 in P-mannopyranosides harbors repulsive steric effects [40]. Glycosyl donors with a participating group at 0 -2 and halide-ion catalytic conditions promote the exclusive formation of (Y man-Carbohydrates in Chemistry and Biology FHzOAc CHzOH HOH& 1 . Ag20.1, AcO & Br -t AcO 2.Ba(OWzb OAc 2 3 Scheme 2. + H O~O Ag2C03 ~ E@&&o, , CH2CI2 Bn OBn Yield: 64% c1 5 6 7 Scheme 3. 13 Stereoselective Synthesis of p-Mannosides 1 -55 to -30°C Br 13 Yield: 87% 14 Scheme 5. Ag silicate 0~~ -15 to25 OC Bn OMP CH,CI, + Br NPhth pphth Yield: 22% 15 16 17 Scheme 6.A more predictable approach to this problem has become possible by van Boeckel's recognition that an electron-withdrawing, acyl substituent at 0-4 of mannosyl donors promotes P-selectivity whereas such substituents at 0 -3 and 0-6 reduce it [52]. Highly reactive donor-acceptor combinations seem exempt from this rule [69, 701-silver silicate-promoted condensation of the mannosyl donor 13 with n-octanol affords the P-linked mannoside 14 in excellent yield even without an acyl substituent at 0-4 (Scheme 5) [69]. Paulsen's acti...

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Definitive chemical evidence for the constitutive ability of Candida albicans serotype A strains to synthesize β‐1,2 linked oligomannosides containing up to 14 mannose residues

Cited by 31 publications

References 36 publications

The Candida albicans Phospholipomannan Is a Family of Glycolipids Presenting Phosphoinositolmannosides with Long Linear Chains of β-1,2-Linked Mannose Residues

The Candida albicans Phospholipomannan Is a Family of Glycolipids Presenting Phosphoinositolmannosides with Long Linear Chains of β-1,2-Linked Mannose Residues

Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans

Stereoselective Synthesis of β‐Mannosides

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