ArticleBiochimica et biophysica acta. Biomembranes2017
Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans.
Article in Biochimica et biophysica acta. Biomembranes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Fungal Sphingolipids: Biosynthesis Pathways, Structural Features and Biological Functions.Journal of fungi (Basel, Switzerland) · 2026Review
- Central Roles of Glucosylceramide in Driving Cancer Pathogenesis.International journal of molecular sciences · 2025Review
- Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.npj antimicrobials and resistance · 2025Review
- Virulence factors released by extracellular vesicles fromFrontiers in cellular and infection microbiology · 2025Review
- Role of sphingolipids in the host-pathogen interaction.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection.PLoS pathogens · 2022Article
- Phenotype to genotype inCurrent research in microbial sciences · 2022Article
- Regulation of sphingolipid synthesis by the G1/S transcription factor Swi4.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Article
- Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris.mSystems · 2021Article
- Functions of Sphingolipids in Pathogenesis During Host-Pathogen Interactions.Frontiers in microbiology · 2021Review
- Sphingolipidomics of drug resistant Candida auris clinical isolates reveal distinct sphingolipid species signatures.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Article
- Glycosphingolipids in Filamentous Fungi: Biological Roles and Potential Applications in Cosmetics and Health Foods.Frontiers in microbiology · 2021Review
- Glucosylceramide Plays a Role in Fungal Germination, Lipid Raft Organization and Biofilm Adhesion of the Pathogenic FungusJournal of fungi (Basel, Switzerland) · 2020Article
- Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders.International journal of molecular sciences · 2020Review
- Antifungal Drug Development: Targeting the Fungal Sphingolipid Pathway.Journal of fungi (Basel, Switzerland) · 2020Review
- Article
- Genome-Scale Metabolic Modeling for Unraveling Molecular Mechanisms of High Threat Pathogens.Frontiers in cell and developmental biology · 2020Review
- Extracellular Vesicles-Connecting Kingdoms.International journal of molecular sciences · 2019Review
- Role of lipid transporters in fungal physiology and pathogenicity.Computational and structural biotechnology journal · 2019Review
- Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
Fungal glucosylceramide (GlcCer) is a plasma membrane sphingolipid in which the sphingosine backbone is unsaturated in carbon position 8 (C8) and methylated in carbon position 9 (C9). Studies in the fungal pathogen, Cryptococcus neoformans, have shown that loss of GlcCer synthase activity results in complete loss of virulence in the mouse model. However, whether the loss of virulence is due to the lack of the enzyme or to the loss of the sphingolipid is not known. In this study, we used genetic engineering to alter the chemical structure of fungal GlcCer and studied its effect on fungal growth and pathogenicity. Here we show that unsaturation in C8 and methylation in C9 is required for virulence in the mouse model without affecting fungal growth in vitro or common virulence factors. However, changes in GlcCer structure led to a dramatic susceptibility to membrane stressors resulting in increased cell membrane permeability and rendering the fungal mutant unable to grow within host macrophages. Biophysical studies using synthetic vesicles containing GlcCer revealed that the saturated and unmethylated sphingolipid formed vesicles with higher lipid order that were more likely to phase separate into ordered domains. Taken together, these studies show for the first time that a specific structure of GlcCer is a major regulator of membrane permeability required for fungal pathogenicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.