Cryptococcus neoformans

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cellular organisms - Eukaryota - Fungi/Metazoa group - Fungi - Dikarya - Basidiomycota - Agaricomycotina - Tremellomycetes - Tremellales - Tremellaceae - Filobasidiella - Filobasidiella/Cryptococcus neoformans species complex - Filobasidiella neoformans

Brief facts

• Cryptococcus neoformans (anamorph) or Filobasidiella neoformans (teleomorph) is an encapsulated fungus that usually grows as a yeast and replicates by budding. It is distributed worldwide and is often found in soil contaminated by avian feces. Inhalation of airborne propagules from an environmental source is main pathway of infection.
• F. neoformans is a causative agent of cryptococcosis, also known as Busse-Buschke disease, a disease that ranges from asymptomatic infection of airways to severe meningitis. The most common route of introduction of the infection is inhalation of fungal spores. The crucial factor of the disease outcome is believed to be not the pathogen's virulence but the immune status of the host. The emergence of the HIV virus promoted C. neoformans from a little-known pathogen to a common killer of immunocompromized patients.
• The fungus has the following essential virulence factors: synthesis of the pigment melanin, development of polysaccaride capsule which helps it to withstand phagocytosis by alveolar macrophages, ability to grow at human temperature (37-39°C), and ability to cross blood-brain barrier. Serotypes can be distinguished by antigen testing and molecular fingerprinting.

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Developmental stages

Life Cycle Stages

• parasexual parasexuality is a form of reproduction in fungi which enables mitotic recombination without meiosis, and usually involves reduction of a diploid to a haploid through whole-chromosome loss; in C. neoformans, in contrast to other fungi with parasexual cycles, meiosis occurs not only during mating but also during monokaryotic fruiting, resulting in recombinant haploid spores
  • monokaryotic
    fruiting the diploid hyphal cells are produced by fusion of haploid nuclei within single mating type; resulting filaments are mononucleate with unfused clamp connections (a short branches connecting one cell to the previous cell in hyphae), i. e. diploidization occurs early in filamentation before formation of the fruiting structures; monokaryotic fruiting predominates in mating type α
  • mating after fusion of cells from different mating types, the resulting hyphal cells contain two nuclei and are linked by fused clamp connections; the diploidization occurs from fusion of the nuclei inside of the fruiting structures
• asexual
  • vegetative growth
    • budding yeast a most common form of the fungus isolated from patients or from the environment
    • filamentous growth form of growth which preceeds sporulation; during this phase fusion of 1n nuclei within one mating type might occur and lead to monokaryotic fruiting

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Tissues

• basidium a terminal fruiting structures inside which the meiosis takes place; each basidium produces four tetrads of haploid spores
  • basidiospore haploid spores emerging from the basidium
• mycelium filamentous form of the fungus
• unicellular organism budding yeast form of the fungus

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Mating types

• mating type a less virulent mating type
• mating type α more virulent type; this type constitutes approximately 96% of all clinical isolates and in co-infections with both mating types is usually the one to enter the central nervous system

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Appendix 1: MATα allele enhances filamentation

Lin X, Huang JC, Mitchell TG, Heitman J. Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation. PLoS Genet. 2006 Nov 17;2(11):e187.

Fruiting in a and α Isolates Is Similar The filamentous isolate B3502a was cultured on V8 medium in the presence of synthetic α pheromone at 22 °C in the dark for two wk. The filamentous edge far from the original yeast growth patch was separated, fixed, and stained with DAPI. (A) The hyphae produced are monokaryotic with unfused clamps. (B) Four long chains of basidiospores were produced during fruiting. (C) Basidia with one, two, or four nuclei at different stages of basidium development were observed. In (A) and (C), the upper panel shows the DIC images, and the lower panel shows the corresponding fluorescent images. Scale bar, 10 μm.

Variation in Filamentous Growth during Fruiting A subset of the fruiting progeny derived from the cross between the nonfilamentous strain B3501α and the filamentous strain B3502a was examined microscopically. Cells were cultured on V8 medium for 25 d. Parental strains and several representative progeny displaying variations in hyphal growth are shown with the strain names listed below them.

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Appendix 2: cryptococcosis of the lung

Perfect JR. Management of cryptococcosis: how are we doing? PLoS Med. 2007 Feb;4(2):e47.

Cryptococcosis of the Lung in a Patient with AIDS Histopathology of lung shows widened alveolar septa containing a few inflammatory cells and numerous yeasts of the fungal pathogen C. neoformans. The inner layer of the yeast capsule stains red. Cryptococcosis is transmitted through inhalation of airborne yeast cells and/or biospores. At risk are the immunocompromised, especially those with HIV infection. Photo: CDC/Dr. Edwin P. Ewing, Jr.

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References

• Lin X, Heitman J. The biology of the Cryptococcus neoformans complex. Nat Rev Microbiol. 2005 Oct;3(10):753-64. PMID: 16704346
• Lin X et al. Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation. PLoS Genet. 2006 Nov 17;2(11):e187. PMID: 17112316
• Idnurm A et al. Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat Rev Microbiol. 2005 Oct;3(10):753-64. PMID: 16132036

Websites

• Wikipedia: Cryptococcus neoformans
• eMedicine: Cryptococcosis

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