ArticleThe EMBO journal1997
Calcineurin is required for virulence of Cryptococcus neoformans.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
263 citing papers in PubMed, 521 citations in OpenAlex.
- Trial
- Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality.The Journal of infectious diseases · 2007Trial
- Molecular remodelling ofJournal of medical microbiology · 2026Article
- Reactive Oxygen Species-Responsive Signaling Networks and Oxidative Stress Adaptation in Critical Priority Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2026Review
- Phosphoproteomics of WHO-Priority Fungal Pathogens: Conserved Signaling Architecture, Pathogen-Specific Outputs, and Therapeutic Vulnerabilities.Pathogens (Basel, Switzerland) · 2026Review
- Article
- A review of the current anti-New microbes and new infections · 2026Review
- Echinocandin tolerance and persistencemBio · 2026Article
- Article
- Frontiers in fungal phosphatases: molecular diversity, regulatory mechanisms, analytical methodologies, ecological significance, and prospects for sustainable utilization.Frontiers in bioengineering and biotechnology · 2026Review
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
- Article
- Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.PLoS biology · 2025Article
- Thermoregulation network governing virulence of a critical human fungal pathogen.bioRxiv : the preprint server for biology · 2025Article
- The pre-mRNA splicing modulator pladienolide B inhibitsmSphere · 2025Article
- Article
- Insights from Mass Spectrometry-Based Proteomics onJournal of fungi (Basel, Switzerland) · 2025Review
- The emerging fungal pathogen Cryptococcus gattii: Epidemiology, pathogenesis, immunomodulatory attributes, and drug susceptibility.PLoS neglected tropical diseases · 2025Review
- The calcineurin pathway regulates extreme thermotolerance, cell membrane and wall integrity, antifungal resistance, and virulence in Candida auris.PLoS pathogens · 2025Article
- Calcineurin controls the cytokinesis machinery during thermal stress inProceedings of the National Academy of Sciences of the United States of America · 2025Article
203 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
6 authors at 1 institution in 1 country.
Funding
Abstract
Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural products that inhibit signal transduction. In T cells and Saccharomyces cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and the resulting complexes inhibit the Ca2+-regulated protein phosphatase calcineurin. We find that growth of the opportunistic fungal pathogen Cryptococcus neoformans is sensitive to CsA and FK506 at 37 degrees C but not at 24 degrees C, suggesting that CsA and FK506 inhibit a protein required for C. neoformans growth at elevated temperature. Genetic evidence supports a model in which immunophilin-drug complexes inhibit calcineurin to prevent growth at 37 degrees C. The gene encoding the C. neoformans calcineurin A catalytic subunit was cloned and disrupted by homologous recombination. Calcineurin mutant strains are viable but do not survive in vitro conditions that mimic the host environment (elevated temperature, 5% CO2 or alkaline pH) and are no longer pathogenic in an animal model of cryptococcal meningitis. Introduction of the wild-type calcineurin A gene complemented these growth defects and restored virulence. Our findings demonstrate that calcineurin is required for C. neoformans virulence and may define signal transduction elements required for fungal pathogenesis that could be targets for therapeutic intervention.
Indexed as
Identifiers
What OpenQuestion holds
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.