SynthesisNature communications2024
Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.
Synthesis in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
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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
7 citing papers in PubMed.
- Primary Cryptococcal Cellulitis With High Antigenemia in an Immunocompromised Host: A Case Report and Laboratory Investigation of the CausativeOpen forum infectious diseases · 2026Article
- Vaccine-Mediated Protection of Mice Against African and Asian Clinical Strains ofJournal of fungi (Basel, Switzerland) · 2025Article
- Global proteomic analysis ofmSystems · 2025Article
- Insights from Mass Spectrometry-Based Proteomics onJournal of fungi (Basel, Switzerland) · 2025Review
- Article
- The hypervirulent Type-1/Type-17 phenotype ofInfection and immunity · 2025Article
- Vacuolar protein sorting-associated protein Vps17 regulates sexual reproduction and virulence ofMycology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
Studies across various pathogens highlight the importance of pathogen genetic differences in disease manifestation. In the human fungal pathogen Cryptococcus neoformans, sequence type (ST) associates with patient outcome. We performed a meta-analysis of four genomic studies and identified overlapping gene regions associated with virulence, suggesting the importance of these gene regions in cryptococcal disease in diverse clinical isolates. We explored the relationship between virulence and strain genetic differences using the cryptococcosis mouse model and a closely related library of ST93 clinical isolates. We identified four in vivo virulence phenotypes: hypervirulence, typical virulence with CNS disease, typical virulence with non-CNS disease, and latent disease. Hypervirulent isolates were clade specific and associated with an interferon gamma (IFNγ) dominated immune response. Using a genome wide association study (GWAS), we identified nine genes with polymorphisms associated with IFNγ production, including the inositol sensor ITR4. The itr4Δ mutant recapitulated the hypervirulence phenotype and ITR4 affects expression of two IFNγ associated genes. Finally, we showed that IFNγ production is associated with SNPs that downregulate ITR4 and with SNP accumulation in other IFNγ associated genes. These data highlight the complex role of pathogen genetics in virulence and identify genes associated with hypervirulence and IFNγ in Cryptococcus neoformans.
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