The structure of Cryptococcus neoformans galactoxylomannan contains beta-D-glucuronic acid

Analytical Services/Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Carbohydrate research (Impact Factor: 1.93). 04/2009; 344(7):915-20. DOI: 10.1016/j.carres.2009.03.003
Source: PubMed

ABSTRACT The structure of galactoxylomannan, a capsular polysaccharide from the opportunistic yeast Cryptococcus neoformans, was re-examined by NMR spectroscopy and GC-MS. The residue that is 3-linked to the side chain galactose and was previously assigned as beta-D-xylose [Vaishnav, V. V.; Bacon, B. E.; O'Neill, M.; Cherniak, R. Carbohydr. Res.1998, 306, 315-330] was determined to be beta-D-glucuronic acid. A revised structure for this polymer is presented, along with a proposal that this compound be termed glucuronoxylomannogalactan (GXMGal).

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Available from: Tamara Doering, Sep 29, 2015
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    • "Cryptococcal PS can be secreted via the protein secretory pathway ( Yoneda and Doering , 2006 ; Panepinto et al. , 2009 ) , or shed from cells in association with vesicular structures ( Rodrigues et al . , 2007 ) , and consists of at least two types of polymers : glucuronoxylomannan ( GXM ) and glucuronoxylomannogalactan ( GXMGal ; Heiss et al . , 2009 ) . Despite the homogenous appearance of the capsule by light microscopy , electron microscopy ( EM ) data suggest that the capsule is a heterogeneous structure , with a clear vertical " stratification " of the matrix into an electron - dense inner layer and an electron - lucent outer layer ( Gates et al . , 2004 ; Bryan et al . , 2005 "
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    ABSTRACT: The fungal pathogen Cryptococcus neoformans causes life-threatening infections in immunocompromised individuals, representing one of the leading causes of morbidity and mortality in AIDS patients. The main virulence factor of C. neoformans is the polysaccharide capsule; however, many fundamental aspects of capsule structure and function remain poorly understood. Recently, important capsule properties were uncovered using optical tweezers and other biophysical techniques, including dynamic and static light scattering, zeta potential and viscosity analysis. This review provides an overview of the latest findings in this emerging field, explaining the impact of these findings on our understanding of C. neoformans biology and resistance to host immune defenses.
    Frontiers in Microbiology 06/2015; 6:640. DOI:10.3389/fmicb.2015.00640 · 3.99 Impact Factor
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    • "GXM is composed of a large backbone of 6-O-acetylated α-1,3-mannose residues with β-D-xylopyranosyl, β-D-glucuronosyl monosubstituted side chains (Cherniak and Sundstrom, 1994). Recently, Heiss et al. (2009) re-examined the structure of C. neoformans GalXM by Nuclear Magnetic Resonance (NMR) spectroscopy and Gas-liquid Chromatography-Mass Spectrometry (GC–MS), and proposed GalXM to be termed glucuronoxylomannogalactan (GXMGal). "
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    ABSTRACT: The capsule is the most important virulence factor of the fungal pathogen Cryptococcus neoformans. This structure consists of highly hydrated polysaccharides, including glucuronoxylomannan (GXM), and galactoxylomannan (GalXM). It is also composed of mannoproteins (MPs) which corresponds to less than 1% of the capsular weight. Despite MPs being the minority and least studied components, four of these molecules with molecular masses of 115, 98, 88, and 84 kDa were identified and characterized as C. neoformans immunoreactive antigens involved in the pathogenesis, and are potential cryptococcosis vaccine candidates. With the aim to describe the adhesive property of MPs, we cloned and expressed the MP84, a mannoprotein with molecular weight of 84 kDa, on Pichia pastoris yeast, and performed interaction assays of C. neoformans with epithelial lung cells, in the presence or absence of capsule components. Two fungal strains, the wild type, NE-241, and a mutant, CAP67, deficient in GXM production, were used throughout this study. The adhesion assays were completed using epithelial lung cells, A549, and human prostate cancer cells, PC3, as a control. We observed that capsulated wild type (NE-241), and acapsular (CAP67) strains adhered significantly to A549 cells, compared with PC3 cells (p < 0.05). GXM inhibits the NE-241 adhesion, but not the CAP67. In contrast, CAP67 adhesion was only inhibited in the presence of MP84. These results demonstrate the involvement of MP in the adhesion of C. neoformans to epithelial lung cells. We conclude that this interaction possibly involves an adhesion-like interaction between MP on the fungal surface and the complementary receptor molecules on the epithelial cells.
    Frontiers in Cellular and Infection Microbiology 08/2014; 4:106. DOI:10.3389/fcimb.2014.00106 · 3.72 Impact Factor
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    • "Besides these surface-exposed enzymes, the polysaccharide capsule is considered to be one of the main virulence factors [12]. The capsule consists mainly of the polysaccharides glu curonoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal) [17] [20], in a mass:ratio of about 10:1 [8]. This capsule enables the yeast-like fungus to survive the harsh environment of the human body by immune evasion and by preventing killing through phagocytosis by macrophages [27] [31]. "
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    ABSTRACT: The human pathogen Cryptococcus neoformans causes meningo-encephalitis. The polysaccharide capsule is an important virulence factor for this yeast-like fungus. Previously, we had shown that disruption of the CAP10 gene encoding a putative xylosyltransferase results in mutant cells that lack most of the capsular polysaccharides on the cell surface, but do not show a typical acapsular phenotype. In contrast to the acapsular cap59 mutant, cap10 did not induce maturation of dendritic cells when exposed to components of the immune system. In order to gain further insight into the causes of this phenotype displayed by the cap10 mutant, we performed a more in-depth phenotypic analysis of the cell wall and surface structures of this mutant compared to the wild type strain and acapsular mutant cap59. Moreover, we analyzed the cap10 mutant and the wild type strain for differential gene expression of, amongst others, enzymes that are involved in biogenesis of cell wall and capsule components. We conclude that a mutation in the CAP10 gene results in a pleiotropic phenotype with effects on different cellular processes affecting, amongst others, cell size, expression of virulence factors and size of extracellular vesicles.
    Research in Microbiology 04/2014; 165(6). DOI:10.1016/j.resmic.2014.04.001 · 2.71 Impact Factor
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