Biosynthesis and Immunogenicity of Glucosylceramide in
            <i>Cryptococcus neoformans</i>
            and Other Human Pathogens

Rhome, Ryan; McQuiston, Travis; Kechichian, Talar; Bielawska, Alicja; Hennig, Mirko; Drago, Monica; Morace, Giulia; Luberto, Chiara; Poeta, Maurizio Del

doi:10.1128/ec.00208-07

Cited by 36 publications

(25 citation statements)

References 107 publications

(112 reference statements)

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“…Because of their unique structural characteristics, fungal GlcCers have sparked much interest in understanding their biological functions in fungal growth, differentiation, and pathogenesis by using forward-and reverse-genetics approaches (27,43). At present, the roles of GlcCers in plantpathogenic fungi remain relatively unknown.…”

Section: Discussionmentioning

confidence: 99%

“…In the proposed overall biosynthetic pathway of fungal GlcCer, the C-9-MT enzymatic step follows the ⌬8-desaturase enzymatic step but precedes the ⌬3-desaturase step and the last GCS enzymatic step (27,43). The structure of C-9-methylated GlcCer of F. graminearum is identical to that of P. pastoris, and the enzymatic steps leading to the synthesis of GlcCer seem to be conserved between the two fungi.…”

mentioning

confidence: 82%

“…It is therefore not surprising that GlcCers are important regulators of pathogenicity in human fungal pathogens (27). However, their roles in plant-fungus interactions are poorly understood.…”

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confidence: 99%

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Sphingolipid C-9 Methyltransferases Are Important for Growth and Virulence but Not for Sensitivity to Antifungal Plant Defensins inFusarium graminearum

et al. 2009

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The C-9-methylated glucosylceramides (GlcCers) are sphingolipids unique to fungi. They play important roles in fungal growth and pathogenesis, and they act as receptors for some antifungal plant defensins. We have identified two genes, FgMT1 and FgMT2, that each encode a putative sphingolipid C-9 methyltransferase (C-9-MT) in the fungal pathogen Fusarium graminearum and complement a Pichia pastoris C-9-MT-null mutant. The ⌬Fgmt1 mutant produced C-9-methylated GlcCer like the wild-type strain, PH-1, whereas the ⌬Fgmt2 mutant produced 65 to 75% nonmethylated and 25 to 35% methylated GlcCer. No ⌬Fgmt1⌬Fgmt2 double-knockout mutant producing only nonmethylated GlcCer could be recovered, suggesting that perhaps C-9-MTs are essential in this pathogen. This is in contrast to the nonessential nature of this enzyme in the unicellular fungus P. pastoris. The ⌬Fgmt2 mutant exhibited severe growth defects and produced abnormal conidia, while the ⌬Fgmt1 mutant grew like the wild-type strain, PH-1, under the conditions tested. The ⌬Fgmt2 mutant also exhibited drastically reduced disease symptoms in wheat and much-delayed disease symptoms in Arabidopsis thaliana. Surprisingly, the ⌬Fgmt2 mutant was less virulent on different host plants tested than the previously characterized ⌬Fggcs1 mutant, which lacks GlcCer synthase activity and produces no GlcCer at all. Moreover, the ⌬Fgmt1 and ⌬Fgmt2 mutants, as well as the P. pastoris strain in which the C-9-MT gene was deleted, retained sensitivity to the antifungal plant defensins MsDef1 and RsAFP2, indicating that the C-9 methyl group is not a critical structural feature of the GlcCer receptor required for the antifungal action of plant defensins.

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Section: Discussionmentioning

confidence: 99%

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confidence: 82%

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Sphingolipid C-9 Methyltransferases Are Important for Growth and Virulence but Not for Sensitivity to Antifungal Plant Defensins inFusarium graminearum

et al. 2009

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“…Fungal GlcCer has unique structural features, including two double bonds at C4 and C8 in the trans conformation and a methyl substituent on C9 in the sphingoid base (Fig. 1C, [21]). The gene encoding sphingolipid 9-methyltransferase is found only in fungi [22].…”

Section: Structure Of Glccermentioning

confidence: 98%

New insights on glucosylated lipids: Metabolism and functions

Ishibashi

Kohyama-Koganeya

Hirabayashi

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

126

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Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids.

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“…Cryptococcus species synthesize glycoproteins with extensive N-and O-linked modifications that may be comparable in mass to the protein itself (7)(8)(9)(10); many of these bear glycosylphosphatidylinositol anchors (11)(12)(13) and are subsequently transferred to covalent linkage with the cell wall. The organism also synthesizes lipids modified with mannose, xylose, and galactose (14,15). C. neoformans thus generates a broad array of cellular glycans and glycoconjugates that are only partially characterized.…”

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confidence: 99%

A Xylosylphosphotransferase of Cryptococcus neoformans Acts in Protein O-Glycan Synthesis

Reilly

Aoki

Wang

et al. 2011

Journal of Biological Chemistry

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Cryptococcal meningoencephalitis is an AIDS-defining illness caused by the opportunistic pathogen Cryptococcus neoformans. This organism possesses an elaborate polysaccharide capsule that is unique among pathogenic fungi, and the glycobiology of C. neoformans has been a focus of research in the field. The capsule and other cellular glycans and glycoconjugates have been described, but the machinery responsible for their synthesis remains largely unexplored. We recently discovered Xpt1p, an enzyme with the unexpected activity of generating a xylosephosphate-mannose linkage. We now demonstrate that this novel activity is conserved throughout the C. neoformans species complex, localized to the Golgi apparatus, and functions in the O-glycosylation of proteins. We also present the first survey of O-glycans from C. neoformans.

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Biosynthesis and Immunogenicity of Glucosylceramide in Cryptococcus neoformans and Other Human Pathogens

Cited by 36 publications

References 107 publications

Sphingolipid C-9 Methyltransferases Are Important for Growth and Virulence but Not for Sensitivity to Antifungal Plant Defensins inFusarium graminearum

Sphingolipid C-9 Methyltransferases Are Important for Growth and Virulence but Not for Sensitivity to Antifungal Plant Defensins inFusarium graminearum

New insights on glucosylated lipids: Metabolism and functions

A Xylosylphosphotransferase of Cryptococcus neoformans Acts in Protein O-Glycan Synthesis

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