Overview

Comprehensive Description

General Description

Colonies are white to dark cream colored, smooth, mucoid, glistening to dull and generally grow slower than Candida. The degree of mucoidness is proportional to the amount of polysaccharide capsule that the fungus produces. Colonies that have small capsules may be wrinkled and granular in appearance. They grow well at 25 C and 37 C. Temperatures above 37 C slow the fungus growth. When grown on media containing diphenolic compounds colonies are brown to black in color.

 

Microscopically yeast cells are globose to ovoid, thick-walled, budding cells that do not produce hyphae or pseudophyphae. Polysaccharide capsules can be seen using India Ink preparation. The capsules can be up to twice the radius of the yeast cell.

 

This genus includes four serotypes A-D. Until recently serotypes A and D were included in Cryptococcus neoformans var. neoformans and serotypes B and C were included in Cryprococcus neoformans var. gattii. However a new variety, var. grubii has been proposed to contain serotype A.

 

The teleomorph of Cryptococcus neoformans var. neoformans is Filobasidiella neoformans var. neoformans and can be induced by placing two isolates of serotype D of opposite mating types in V-8 juice agar. The yeast cells will conjugate and produce long hyphae with clamp connections, haustria-like hyphae, and dolipore (nuclei cannot pass through) septa.

 

Terminal basidia form from the hyphae in about three weeks. The basidia are slender, subglobose to club-shaped, and non-septate.

 

Basidiospores are sessile, slightly rough, oval, pyriform, cylindrical to elliptical, uninucleate, and produced in chains by basipetal budding at the apex of the basidia, i.e., at the base of the chain.

 

 

a | The fungal polysaccharide capsule is produced in response to environmental cues, in this case after five days in the rabbit central nervous system. India ink (black) is excluded from the fungus by the capsule. b | The fungus produces melanin in the presence of diphenolic molecules (such as L-DOPA) to turn brown or black, in contrast to the common human pathogenic yeast Candida albicans, which forms white colonies on this medium. c | The fungus is a basidiomycete, able to produce filaments when two opposite mating partners (KN99 MAT and Bt63 MATa) are co-cultured, producing four chains of haploid basidiospores from a basidium (inset).

 

Reprinted by permission from Macmillan Publishers Ltd: [Nature Reviews Microbiology 3, 753-764] (Idnurm, 2005), copyright (2005)

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Distribution

It is ubiquitous. It is often a laboratory contaminant.

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Physical Description

Diagnostic Description

The ability to grow at 37 C distinguishes it from other Cryptococcus species however a few temperature sensitive mutants are possible.

 

C. neoformans var. gattii is only found on Eucalyptus camaldulensis. Some research considers it to be a distinct species.

 

Canavanine-glycine-bromthymol blue (CGB) medium can be used to distinguish from var. gattii. C. neoformans var. gattii will produce a blue color on the media.

 

In histopathology sections var. gattii produces more elongated, oval, or elliptical cells where var. neoformans produces more strictly globose cells.

 

Filobasidiella neoformans var. bacillispora produces smooth, rod-shaped basidiospores and no haustrioid hyphae.

 

C. neoformans var. grubii cannot utilize thymine. Also significant genetic differences using DNA fingerprinting have also been reported. (Franzot et. al.,1999)

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Look Alikes

It must be distinguished from all other clinically important yeasts.

 

An India Ink stain can be used to see capsule production.

 

The absence of hyphae or pseudohyphae distinguishes it from Candida albicans.

 

The lack of arthroconidia distinguishes it from Trichosporon and Geotrichum.

 

It cannot ferment sugars.

 

The ability to assimilate insitol distinguishes it from another common basidiomycetous yeast, Rhodotorula.

 

The ability to assimilate insitol and produce urease distinguishes it from Candida glabrata.

 

The ability to produce melanin on media containing diphenolic compounds can also be a distinguishing factor.

 

Latex agglutination tests can also be used to identify the serotype.

 

Commercially available DNA probes are useful to laboratories that need rapid and accurate identification of Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, and C. neoformans.

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Ecology

Habitat

It is an opportunistic pathogen in humans.

 

It has been isolated from soil, plants, fruit, milk, skin, feces of people in normal health, and most notoriously pigeon dung. It has also been isolated from many other bird droppings as well including chickens, canaries, parrots, and swallows. Initially it was thought that pigeons were carriers of the disease however it has been seen that there is not an increase in disease in areas with a lot of pigeon dung. Pigeons do not become infected with the disease because their body temperature is too high and the yeast simply pass through their gut and grows in their dung.

 

It may be more useful to find the ecological niche of the teleomorph because basidiospores are dry, readily airborne, and small enough to fit inside the alveoli of the lungs.

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Molecular Biology and Genetics

Molecular Biology

Barcode data: Cryptococcus neoformans var. neoformans

The following is a representative barcode sequence, the centroid of all available sequences for this species.


There is 1 barcode sequence available from BOLD and GenBank.   Below is the sequence of the barcode region Cytochrome oxidase subunit 1 (COI or COX1) from a member of the species.  See the BOLD taxonomy browser for more complete information about this specimen.  Other sequences that do not yet meet barcode criteria may also be available.

TATCTGATCTTTGCTATCTTTACTGGTCTTCTAGGTACAGCTTTCTCTGTTCTTATCCGACTTGAACTGTCTGGAGCTGGTAACCAATTTCTAAACGGTGACCACCAACTATACAATGTAATCGCTACATCTCACGGTATTTTCATGATTTACTTCATG---GTAGTACCTGCTATGGCTGGT---TTTGGTAACTATATGGTTCCTGTTCTTATTGGTGCTCCTGATATGGCTTTCCCACGACTGAATAATGTATCATTCTGGATTCTTCCTCCTGCTATTGTTCTTATCGTTTCAAGTGTATTCGTAGAACAAGGTATGGGTACAGGT------------TGGACTCTTTACATGCCTATTACAGGTGTACAATCTCATTCAGGTGGATCAGTAGATCTAGCTATTTTCTCACTACACCTTTCAGGTATTTCATCAATGCTAGGTGCTATGAACATTATCACTACTATTATTAACATGCGAGCTCCTGGTATGACACTACACAAGATGCCTCTATTTGTATGGGCTATGCTATTCCAATCAATTATCATTATCCTATGTATCCCAGTTCTAGCTGGTGCACTAACAATGATTATTACAGATCGAAACTTCAACACATCATTCTACGACCCAGCTGGTGGTGGTGATCCAGTTCTATATGAACACCTC
-- end --

Download FASTA File
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Statistics of barcoding coverage: Cryptococcus neoformans var. neoformans

Barcode of Life Data Systems (BOLDS) Stats
Public Records: 1
Specimens with Barcodes: 1
Species With Barcodes: 1
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Relevance to Humans and Ecosystems

Benefits

Uses

C. neoformans is an opportunistic pathogen that commonly causes a disease called cryptococcosis in AIDS patients or people who are taking corticosteroids, have organ transplants, or are on chemotherapy drugs.

 

Cryptococcosis or Busse-Buschke disease is acquired by inhalation of the yeast cells or basidiospores into the lungs. The infection is subacute or chronic. The chronic form is most commonly found in the brain causing meningoencephalitis. This form is the most common among AIDS patients. The disease can also occur in the lungs, skin, bones, joints, eyes, myocardium, urinary tract, and prostate gland (see image).

 

 

Histology of the biopsy specimen of the prostate. (a) Granulomatous lesion of the prostate (HE, 200). (b) High magnification of the granuloma. Small round organisms are scattered in granulomas (HE, 400). © Grocott’s methenamine silver demonstrates numerous yeast-form pathogens in the granulomatous lesion. (d) The pathogen is clearly stained with periodic acid-Schiff with diastase treatment. (e) Fontana-Masson stain demonstrates melanin in the cell wall. (f) The mucoid capsule of the pathogen is stained with mucicarmine.

 

Reprinted by permission from Macmillan Publishers Ltd: [Nature Reviews Microbiology 3, 753-764] (Idnurm, 2005), copyright (2005)

 

Meningoencephalitis is the most deadly form of this disease. It can progress rapidly and suddenely induce a coma. Tissue that is in contact with the yeast becomes compressed from the fungus growth but is not necrotic, hemorrhagic, or engorged with blood.

 

Pulmonary cryptococcosis can be misdiagnosed as Tuberculosis. Treatment with an antibiotic causes the fungal infection to worsen. Upon x-ray fungus can be seen forming extensive lesions in the lungs.

 

Infection of the skin is either a milder form of the disease or is a sign of a more extensive infection somewhere else in the body. Skin infections show up as small papules and either resolve one their own or are surgically removed.

 

C. neoformans has some virulence factors that make it a successful pathogen. The ability to grow at body temperature give it the ability to become a pathogen. The polysaccharide capsule protects it from phagocytosis. The production of melanin from diphenolic compounds is also considered a virulence factor because the melanin accumulates in the cell wall and protects the yeast from free radicals produced by host cells.

 

Treatment for cryptococcosis is Amphoteracin B followed by 5-Fluorocytosine. It is not easily cured in immunosuppressed patients.

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