ArticleInfection and immunity2006
The cryptococcal enzyme inositol phosphosphingolipid-phospholipase C confers resistance to the antifungal effects of macrophages and promotes fungal dissemination to the central nervous system.
Article in Infection and immunity, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 110 citations in OpenAlex.
- Cryptococcal dumbbell inflammatory pseudotumor mimicking skull histiocytic sarcoma in immunocompetent patient.Surgical neurology international · 2026Article
- Review of Risk Factors and Factors Influencing Outcomes of Cryptococcal Meningitis in Persons Living with HIV.Infection and drug resistance · 2026Review
- Pathogenicity and virulence of Cryptococcus neoformans from an environmental perspective.Virulence · 2025Review
- Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.npj antimicrobials and resistance · 2025Review
- Elements of dissemination in cryptococcosis.mBio · 2024Review
- Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques.Journal of fungi (Basel, Switzerland) · 2024Review
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- Sterylglucosides in Fungi.Journal of fungi (Basel, Switzerland) · 2022Review
- Mechanisms of fungal dissemination.Cellular and molecular life sciences : CMLS · 2021Review
- Functions of Sphingolipids in Pathogenesis During Host-Pathogen Interactions.Frontiers in microbiology · 2021Review
- Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans.Nature communications · 2020Article
- Animal Models ofFrontiers in immunology · 2020Review
- New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis.Current neurology and neuroscience reports · 2019Review
- Article
- Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans.Journal of fungi (Basel, Switzerland) · 2018Review
- The AGC Kinase YpkA Regulates Sphingolipids Biosynthesis and Physically Interacts With SakA MAP Kinase inFrontiers in microbiology · 2018Article
- Mechanisms ofFrontiers in immunology · 2018Review
- Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans.Biochimica et biophysica acta. Biomembranes · 2017Article
- It's not all about us: evolution and maintenance of Cryptococcus virulence requires selection outside the human host.Yeast (Chichester, England) · 2017Article
- Lipid Flippase Subunit Cdc50 Mediates Drug Resistance and Virulence in Cryptococcus neoformans.mBio · 2016Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In recent years, sphingolipids have emerged as critical molecules in the regulation of microbial pathogenesis. In fungi, the synthesis of complex sphingolipids is important for the regulation of pathogenicity, but the role of sphingolipid degradation in fungal virulence is not known. Here, we isolated and characterized the inositol phosphosphingolipid-phospholipase C1 (ISC1) gene from the fungal pathogen Cryptococcus neoformans and showed that it encodes an enzyme that metabolizes fungal inositol sphingolipids. Isc1 protects C. neoformans from acidic, oxidative, and nitrosative stresses, which are encountered by the fungus in the phagolysosomes of activated macrophages, through a Pma1-dependent mechanism(s). In an immunocompetent mouse model, the C. neoformans Deltaisc1 mutant strain is almost exclusively found extracellularly and in a hyperencapsulated form, and its dissemination to the brain is remarkably reduced compared to that of control strains. Interestingly, the dissemination of the C. neoformans Deltaisc1 strain to the brain is promptly restored in these mice when alveolar macrophages are pharmacologically depleted or when infecting an immunodeficient mouse in which macrophages are not efficiently activated. These studies suggest that Isc1 plays a key role in protecting C. neoformans from the intracellular environment of macrophages, whose activation is important for preventing fungal dissemination of the Deltaisc1 strain to the central nervous system and the development of meningoencephalitis.
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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.