ArticlePloS one2011
Surface localization of glucosylceramide during Cryptococcus neoformans infection allows targeting as a potential antifungal.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting ceramide synthases for the development of new antifungals.Structure (London, England : 1993) · 2025Article
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Comprehensive genome-scale metabolic model of the human pathogenFrontiers in bioinformatics · 2023Article
- Functions of Sphingolipids in Pathogenesis During Host-Pathogen Interactions.Frontiers in microbiology · 2021Review
- Immunization Strategies for the Control of Histoplasmosis.Current tropical medicine reports · 2019Article
- Recent progress in the strategic incorporation of fluorine into medicinally active compounds.Journal of fluorine chemistry · 2019Article
- Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans.Biochimica et biophysica acta. Biomembranes · 2017Article
- Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers.Scientific reports · 2017Article
- Sphingolipids as targets for treatment of fungal infections.Future medicinal chemistry · 2016Review
- Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis.PloS one · 2016Article
- Transmembrane transporter expression regulated by the glucosylceramide pathway in Cryptococcus neoformans.BMC research notes · 2015Article
- Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids.mBio · 2015Article
- Inositol phosphosphingolipid phospholipase C1 regulates plasma membrane ATPase (Pma1) stability in Cryptococcus neoformans.FEBS letters · 2014Article
- Synthesis and biological properties of fungal glucosylceramide.PLoS pathogens · 2014Review
- Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens.Mycopathologia · 2012Article
- Unravelling secretion in Cryptococcus neoformans: more than one way to skin a cat.Mycopathologia · 2012Review
- Detection of antibody against fungal glucosylceramide in immunocompromised patients: a potential new diagnostic approach for cryptococcosis.Mycopathologia · 2012Article
- Methylation of glycosylated sphingolipid modulates membrane lipid topography and pathogenicity of Cryptococcus neoformans.Cellular microbiology · 2012Article
- Vesicular transport systems in fungi.Future microbiology · 2011Review
- Role of glucose in the expression of Cryptococcus neoformans antiphagocytic protein 1, App1.Eukaryotic cell · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cryptococcus neoformans (Cn) is a significant human pathogen that, despite current treatments, continues to have a high morbidity rate especially in sub-Saharan Africa. The need for more tolerable and specific therapies has been clearly shown. In the search for novel drug targets, the gene for glucosylceramide synthase (GCS1) was deleted in Cn, resulting in a strain (Δgcs1) that does not produce glucosylceramide (GlcCer) and is avirulent in mouse models of infection. To understand the biology behind the connection between virulence and GlcCer, the production and localization of GlcCer must be characterized in conditions that are prohibitive to the growth of Δgcs1 (neutral pH and high CO(2)). These prohibitive conditions are physiologically similar to those found in the extracellular spaces of the lung during infection. Here, using immunofluorescence, we have shown that GlcCer localization to the cell surface is significantly increased during growth in these conditions and during infection. We further seek to exploit this localization by treatment with Cerezyme (Cz), a recombinant enzyme that metabolizes GlcCer, as a potential treatment for Cn. Cz treatment was found to reduce the amount of GlcCer in vitro, in cultures, and in Cn cells inhabiting the mouse lung. Treatment with Cz induced a membrane integrity defect in wild type Cn cells similar to Δgcs1. Cz treatment also reduced the in vitro growth of Cn in a dose and condition dependent manner. Finally, Cz treatment was shown to have a protective effect on survival in mice infected with Cn. Taken together, these studies have established the legitimacy of targeting the GlcCer and other related sphingolipid systems in the development of novel therapeutics.
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