ArticleProceedings of the National Academy of Sciences of the United States of America2009
The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03112031 (A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis), which is not on this map. Cited by 120 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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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.
A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis
Who cites it
120 citing papers in PubMed.
- Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis.The Journal of clinical investigation · 2014Trial
- Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection.PLoS biology · 2026Article
- Pathogenicity and virulence of Cryptococcus neoformans from an environmental perspective.Virulence · 2025Review
- Influence of the agrochemical benomyl on Cryptococcus gattii-plant interaction in vitro and in vivo.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- The interplay between electron transport chain function and iron regulatory factors influences melanin formation inmSphere · 2024Article
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- Group I introns: Structure, splicing and their applications in medical mycology.Genetics and molecular biology · 2024Article
- RNA-containing extracellular vesicles in infection.RNA biology · 2024Review
- Mitogenome Variations in a Global Population ofJournal of fungi (Basel, Switzerland) · 2023Article
- Characteristics and potential clinical applications of the extracellular vesicles of human pathogenic Fungi.BMC microbiology · 2023Review
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- The Cryptococcus gattii species complex: Unique pathogenic yeasts with understudied virulence mechanisms.PLoS neglected tropical diseases · 2022Review
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- Mitochondrial genomes of the human pathogens Coccidioides immitis and Coccidioides posadasii.G3 (Bethesda, Md.) · 2021Article
- Associations betweenJournal of fungi (Basel, Switzerland) · 2021Review
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- Application of an optimized annotation pipeline to the Cryptococcus deuterogattii genome reveals dynamic primary metabolic gene clusters and genomic impact of RNAi loss.G3 (Bethesda, Md.) · 2021Article
- Glucuronoxylomannan in the Cryptococcus species capsule as a target for Chimeric Antigen Receptor T-cell therapy.Cytotherapy · 2021Article
- Mitonuclear Genetic Interactions in the BasidiomyceteFrontiers in fungal biology · 2021Article
60 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we show that the Vancouver Island outbreak (VIO) isolates have dramatically increased their ability to replicate within macrophages of the mammalian immune system in comparison with other C. gattii strains. We further demonstrate that such enhanced intracellular parasitism is directly linked to virulence in a murine model of cryptococcosis, suggesting that this phenotype may be the cause of the outbreak. Finally, microarray studies on 24 C. gattii strains reveals that the hypervirulence of the VIO isolates is characterized by the up-regulation of a large group of genes, many of which are encoded by mitochondrial genome or associated with mitochondrial activities. This expression profile correlates with an unusual mitochondrial morphology exhibited by the VIO strains after phagocytosis. Our data thus demonstrate that the intracellular parasitism of macrophages is a key driver of a human disease outbreak, a finding that has significant implications for a wide range of other human pathogens.
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