Evidence for different mannosylation processes involved in the association of  -1,2-linked oligomannosidic epitopes in Candida albicans mannan and phospholipomannan

Trinel, Pierre-André; Cantelli, C.; Bernigaud, Annie; Jouault, Thierry; Poulain, Daniel

doi:10.1099/13500872-142-8-2263

Cited by 16 publications

(11 citation statements)

References 23 publications

(14 reference statements)

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“…This antigen, named phopholipomannan (17), is expressed only in C. albicans and C. tropicalis, which are the most pathogenic Candida species (25). PLM is synthesized by C. albicans including under growth conditions that prevent association of ␤-1,2-linked oligomannosides to phosphopeptidomannan (30). Recent experiments have shown that C. albicans, in contact with macrophages, shed large amounts of PLM, which triggers an intense phosphotyrosine kinase-dependent signaling pathway and the secretion of TNF-␣ (19).…”

Section: Discussionmentioning

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: 99%

“…3 H]Inositol-Preliminary characterization of C. albicans PLM was made through chloroform/methanol/water extraction procedure and Western blot analysis (30). When the same extraction procedure was applied to [ 3 H]mannose-labeled Fr.…”

Section: Tlc Analysis Of C Albicans Extracts Showed That Plm Correspmentioning

confidence: 99%

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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“…At the moment, the presence of ␤-1,2 oligomannosides has only been chemically proven in PPM and PLM (6,8). It is obvious from a large number of studies where blots were probed with anti-␤-1,2 oligomannoside monoclonal antibodies that, besides PPM and PLM, and depending on the growth conditions, ␤-1,2 oligomannoside epitopes are also expressed on a wide range of cell wall proteins where they generally co-localize with ␣-oligomannoside epitopes (7)(8)(9)26). In parallel, several C. albicans cell wall proteins have been shown to play an important role in pathogenesis or cell wall organization/remodeling.…”

Section: Fig 4 Mit1 Deletion Does Not Affect Cell Morphogenesismentioning

confidence: 99%

“…Western blots of C. albicans cell wall extracts show that ␤-oligomannoside epitopes co-localize with ␣-oligomannoside epitopes on mannosylated proteins (7) and are electively expressed on low molecular weight antigens that have been characterized as phospholipomannan (PLM) (8). Besides PPM, PLM is the second C. albicans molecule in which the presence of ␤-1,2 oligomannosides has been demonstrated chemically (9). PLM appears as a member of the cell membrane MIPC family from which it diverges by the addition of mannose and phosphate linking long linear chains of ␤-mannosides (10).…”

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confidence: 99%

Inactivation of CaMIT1 Inhibits Candida albicans Phospholipomannan β-Mannosylation, Reduces Virulence, and Alters Cell Wall Protein β-Mannosylation

Mille

Janbon

Delplace

et al. 2004

Journal of Biological Chemistry

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Studies on Candida albicans phospholipomannan have suggested a novel biosynthetic pathway for yeast glycosphingolipids. This pathway is thought to diverge from the usual pathway at the mannose-inositol-phospho-ceramide (MIPC) step. To confirm this hypothesis, a C. albicans gene homologue for the Saccharomyces cerevisiae SUR1 gene was identified and named MIT1 as it coded for GDP-mannose:inositol-phospho-ceramide mannose transferase. Two copies of this gene were disrupted. Western blots of cell extracts revealed that strain mit1⌬ contained no PLM. Thin layer chromatography and mass spectrometry confirmed that mit1⌬ did not synthesize MIPC, demonstrating a role of MIT1 in the mannosylation of C. albicans IPCs. As MIT1 disruption prevented downstream ␤-1,2 mannosylation, mit1⌬ represents a new C. albicans mutant affected in the expression of these specific virulence attributes, which act as adhesins/immunomodulators. mit1⌬ was less virulent during both the acute and chronic phases of systemic infection in mice (75 and 50% reduction in mortality, respectively). In vitro, mit1⌬ was not able to escape macrophage lysis through down-regulation of the ERK1/2 phosphorylation pathway previously shown to be triggered by PLM. Phenotypic analysis also revealed pleiotropic effects of MIT1 disruption. The most striking observation was a reduced ␤-mannosylation of phosphopeptidomannan. Increased ␤-mannosylation of mannoproteins was observed under growth conditions that prevented the association of ␤-oligomannosides with phosphopeptidomannan, but not with PLM. This suggests that C. albicans has strong regulatory mechanisms associating ␤-oligomannoses with different cell wall carrier molecules. These mechanisms and the impact of the different presentations of ␤-oligomannoses on the host response need to be defined.

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“…It encompasses a large repertoire of antigenic oligomannose epitopes whose specificity is determined by the nature of the linkage between mannose residues and the length of the oligomannose chain (35). These epitopes are associated with a large variety of different yeast carrier molecules and may be species specific or shared by several species (3,(36)(37)(38). A clear-cut discrimination between ␣-and ␤-linked mannose residues is made by mammalian immune systems and endogenous lectins (11).…”

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confidence: 99%

Increased Sensitivity of Mannanemia Detection Tests by Joint Detection of α- and β-Linked Oligomannosides during Experimental and Human Systemic Candidiasis

et al. 2004

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An enzyme immunoassay (EIA)-the commercially available PlateliaCandida antigen test-developed for the diagnosis of systemic candidiasis is based on the detection of ␣-linked oligomannose residues (␣-Man) released from Candida cells into the serum. This test has good specificity but has to be repeated frequently because of the rapid clearance of detectable mannanemia. We have developed a second EIA based on detection of beta-linked oligomannoses (␤-Man), since ␤-Man are linked to different Candida molecules and interact differently with the host immune system and endogenous lectins and should therefore present different kinetics of serum clearance. In a guinea pig model of Candida albicans systemic infection, the relative amounts of detectable ␣-and ␤-Man differed considerably according to the virulence of the strain, the infecting dose, and the time after challenge that serum samples were drawn. Detection of ␣-Man was more sensitive per serum sample than that of ␤-Man, and the sensitivity for the combination reached 90%. The same tests were applied to 90 sera from 26 patients selected retrospectively for having been infected with the most-pathogenic Candida species: C. albicans (19), C. tropicalis (4), and C. glabrata (3). A total of 22 patients had positive antigenemia, 4 had ␣-mannanemia, 4 had ␤-mannanemia, and 14 showed the presence of both. For the patients showing the presence of both forms of mannanemia, the use of both tests enhanced the duration of the detection of mannanemia. Mannanemia was correlated with early clinical symptoms and isolation of Candida in culture, which occurred in 55% of the patients at an average of 4.7 days after the first positive mannanemia test result. A combination of the two tests had a cumulated specificity of 95%, and positive and negative predictive values were 79 and 97%, respectively. These findings provide evidence for different kinetics of ␤-and ␣-Man circulation during experimental and human candidiasis and suggest the joint detection of both types of epitopes as a rational approach contributing to increases in the sensitivity and earliness of diagnosis.Systemic infections caused by Candida species are an increasing problem in clinical practice. Depending on the medical specialty, Candida species are the fourth or fifth most commonly recovered pathogens in blood cultures (27), with attributable mortality rates for candidemia of 40 to 60% (28, 41). The increasing incidence of systemic candidiasis and high mortality rates has been accompanied by escalating costs of prophylactic, preemptive, and empirical antifungal therapy (6, 7). These medical and economic problems are related to difficulties in establishing an early and specific diagnosis of infection (30, 31). The detection of several Candida-derived molecules in the serum samples of patients has been reported to be of diagnostic value. These molecules include metabolites (29, 43), proteins (25), nucleic acids (8,22), and polysaccharides (either glucans or mannans) (25,26,33). Mannan is a large, complex, and highly i...

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Evidence for different mannosylation processes involved in the association of -1,2-linked oligomannosidic epitopes in Candida albicans mannan and phospholipomannan

Cited by 16 publications

References 23 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

Inactivation of CaMIT1 Inhibits Candida albicans Phospholipomannan β-Mannosylation, Reduces Virulence, and Alters Cell Wall Protein β-Mannosylation

Increased Sensitivity of Mannanemia Detection Tests by Joint Detection of α- and β-Linked Oligomannosides during Experimental and Human Systemic Candidiasis

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