The Genome of the Basidiomycetous Yeast and Human Pathogen Cryptococcus neoformans

Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.
Science (Impact Factor: 33.61). 03/2005; 307(5713):1321-4. DOI: 10.1126/science.1103773
Source: PubMed


Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its approximately 20-megabase genome, which contains approximately 6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions. The presence of these transposons may drive karyotype instability and phenotypic variation. C. neoformans encodes unique genes that may contribute to its unusual virulence properties, and comparison of two phenotypically distinct strains reveals variation in gene content in addition to sequence polymorphisms between the genomes.

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    • "To investigate the impact of hyphal development during unisexual reproduction we utilized the serotype D hyperfilamentous strain XL280α. XL280α is a haploid progeny of two well-validated and sequenced sibling strains, a hypo-filamentous isolate B3501α and a self-filamentous isolate of strain B3502a (which is congenic with the congenic pair JEC21α/JEC20a) [38], [44], [51]. In previous studies we sequenced the XL280α genome and found that it shares 99.88% overall genetic identity with the JEC21α parental strains. "
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    ABSTRACT: Cryptococcus neoformans is a human fungal pathogen that causes lethal infections of the lung and central nervous system in immunocompromised individuals. C. neoformans has a defined bipolar sexual life cycle with a and α mating types. During the sexual cycle, which can occur between cells of opposite mating types (bisexual reproduction) or cells of one mating type (unisexual reproduction), a dimorphic transition from yeast to hyphal growth occurs. Hyphal development and meiosis generate abundant spores that, following inhalation, penetrate deep into the lung to enter the alveoli, germinate, and establish a pulmonary infection growing as budding yeast cells. Unisexual reproduction has been directly observed only in the Cryptococcus var. neoformans (serotype D) lineage under laboratory conditions. However, hyphal development has been previously associated with reduced virulence and the serotype D lineage exhibits limited pathogenicity in the murine model. In this study we show that the serotype D hyperfilamentous strain XL280α is hypervirulent in an animal model. It can grow inside the lung of the host, establish a pulmonary infection, and then disseminate to the brain to cause cryptococcal meningoencephalitis. Surprisingly, this hyperfilamentous strain triggers an immune response polarized towards Th2-type immunity, which is usually observed in the highly virulent sibling species C. gattii, responsible for the Pacific Northwest outbreak. These studies provide a technological advance that will facilitate analysis of virulence genes and attributes in C. neoformans var. neoformans, and reveal the virulence potential of serotype D as broader and more dynamic than previously appreciated.
    PLoS ONE 08/2014; 9(8):e104432. DOI:10.1371/journal.pone.0104432 · 3.23 Impact Factor
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    • "This data from the closely related VNIV (serotype D) laboratory strains JEC21 and B-3501A revealed the 20 Mb haploid genome to consist of 14 chromosomes ranging in size from 762 kb to 2.3 Mb (Fraser et al. 2005b; Loftus et al. 2005). With .6500 "
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    ABSTRACT: Cryptococcus neoformans and Cryptococcus gattii are the two etiologic agents of cryptococcosis. They belong to the phylum Basidiomycota and can be readily distinguished from other pathogenic yeasts such as Candida by the presence of a polysaccharide capsule, formation of melanin, and urease activity, which all function as virulence determinants. Infection proceeds via inhalation and subsequent dissemination to the central nervous system to cause meningoencephalitis. The most common risk for cryptococcosis caused by C. neoformans is AIDS, whereas infections caused by C. gattii are more often reported in immunocompetent patients with undefined risk than in the immunocompromised. There have been many chapters, reviews, and books written on C. neoformans. The topics we focus on in this article include species description, pathogenesis, life cycle, capsule, and stress response, which serve to highlight the specializations in virulence that have occurred in this unique encapsulated melanin-forming yeast that causes global deaths estimated at more than 600,000 annually.
    Cold Spring Harbor Perspectives in Medicine 07/2014; 4(7). DOI:10.1101/cshperspect.a019760 · 9.47 Impact Factor
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    • "The predicted genes (proteins) were clustered into orthologous groups using OrthoMCL version 2.0 software with default parameters [19]. Orthologs from Aspergillus nidulans [20], C. cinerea [21], Cryptococcus neoformans [22], L. bicolor [23], Neurospora crassa [24], Phanerochaete chrysosporium [25], Postia placenta [26], Saccharomyces cerevisiae, [27], S. commune [2], and Ustilago maydis [28] were analyzed. All-versus-all protein comparison was accomplished using the BLASTP module of NCBI BLAST software (version 2.2.20) with E-value cutoff at 0.001. "
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    ABSTRACT: Flammulina velutipes is a fungus with health and medicinal benefits that has been used for consumption and cultivation in East Asia. F. velutipes is also known to degrade lignocellulose and produce ethanol. The overlapping interests of mushroom production and wood bioconversion make F. velutipes an attractive new model for fungal wood related studies. Here, we present the complete sequence of the F. velutipes genome. This is the first sequenced genome for a commercially produced edible mushroom that also degrades wood. The 35.6-Mb genome contained 12,218 predicted protein-encoding genes and 287 tRNA genes assembled into 11 scaffolds corresponding with the 11 chromosomes of strain KACC42780. The 88.4-kb mitochondrial genome contained 35 genes. Well-developed wood degrading machinery with strong potential for lignin degradation (69 auxiliary activities, formerly FOLymes) and carbohydrate degradation (392 CAZymes), along with 58 alcohol dehydrogenase genes were highly expressed in the mycelium, demonstrating the potential application of this organism to bioethanol production. Thus, the newly uncovered wood degrading capacity and sequential nature of this process in F. velutipes, offer interesting possibilities for more detailed studies on either lignin or (hemi-) cellulose degradation in complex wood substrates. The mutual interest in wood degradation by the mushroom industry and (ligno-)cellulose biomass related industries further increase the significance of F. velutipes as a new model.
    PLoS ONE 04/2014; 9(4):e93560. DOI:10.1371/journal.pone.0093560 · 3.23 Impact Factor
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