Cryptococcus neoformans

Teleomorph: Filobasidiella neoformans

This species has two varieties: C. neoformans var. grubii [serotype A] and C. neoformans var. neoformans [serotype D].

C. neoformans var. grubii [serotype A] has a world-wide distribution. It has been isolated from various sources in nature and is noted for its association with accumulations of avian guano, especially with pigeon excreta.   The fungus has also been isolated from the dung of caged birds including canaries, parrots and budgerigars.   Other environmental isolations of C. neoformans var. grubii have been from rotting vegetables, fruits and fruit juices, wood, dairy products and soil.

C. neoformans var. neoformans [serotype D] has a more restricted distribution with infections being more prevalent in France, Italy and Denmark. Moreover, infections are more strongly correlated to older patients, the skin, and the use of corticosteroids (Franzot et al. 1999).

Creatinine dextrose bromothymol blue thymine (CDBT) agar is the medium of choice for the differentiation of Cryptococcus neoformans var. neoformans and Cryptococcus neoformans var. grubii. Cryptococcus neoformans var. neoformans grows as bright red colonies, turning the medium a bright orange after 5 days (Irokanulo et al. 1994).

Basidiospores of Filobasidiella neoformans the teleomorph of C. neoformans.

Culture of C. neoformans

India ink preparation showing capsules of C. neoformans

Bird seed agar plate showing brown colonies of C. neoformans and white colonies of Candida albicans.

Culture: Colonies (SDA) cream-coloured smooth, mucoid yeast-like colonies.

Microscopy: Globose to ovoid budding yeast-like cells 3.0-7.0 x 3.3- 7.9 µm.

India Ink Preparation: Positive - Distinct, wide gelatinous capsules are present.

Dalmau Plate Culture on Cornmeal and Tween 80 Agar: Budding yeast cells only. No pseudohyphae present.

Bird Seed Agar: Colonies turn dark brown in colour as colonies selectively absorb a brown pigment from this media (Staib, 1987).

Canavanine-Glycine-Bromothymol Blue (CGB) Agar: leaves this medium unchanged.

Creatinine dextrose bromothymol blue thymine (CDBT) agar: Cryptococcus neoformans var. neoformans grows as bright red colonies, turning the medium a bright orange after 5 days. No colour change is observed for C. neoformans var. grubii.

Physiological Tests:

Germ Tube test is Negative
Hydrolysis of Urea is Positive
Growth on Cycloheximide medium is Negative
Growth at 37C is Weakly Positive

Fermentation Reactions: Where fermentation means the production of gas and is independent of pH changes.

Negative: Glucose; Sucrose; Lactose; Galactose; Maltose; Trehalose.

Assimilation Tests:

Positive: Glucose; Galactose; Maltose; Sucrose; Trehalose; D-Xylose; Melezitose; Raffinose (weak); Cellobiose (weak); Inositol; L-Rhamnose; D-Arabinose; L-Arabinose (delayed); D-Ribose (weak); Galactitol (delayed); D-Mannitol; D-Glucitol.
Variable: Soluble Starch; Glycerol; Succinic acid; Ribitol; L-Sorbose; Salicin; Citric acid; DL-Lactic acid.
Negative: Potassium nitrate; Lactose; Melibiose; Erythritol.

MIC data is limited.  Antifungal susceptibility testing of individual strains is recommended.

Clinical significance:

In humans, C. neoformans affects immunocompromised hosts predominantly and is the commonest cause of fungal meningitis; worldwide, 7-10% of patients with AIDS are affected. AIDS associated cryptococcosis accounts for 50% of all cryptococcal infections reported annually and usually occurs in HIV patients when their CD4 lymphocyte count is below 200/mm3. Meningitis is the predominant clinical presentation with fever and headache as the most common symptoms. Secondary cutaneous infections occur in up to 15% of patients with disseminated cryptococcosis and often indicate a poor prognosis. Lesions usually begin as small papules that subsequently ulcerate, but may also present as abscesses, erythematous nodules, or cellulitis. This species is found in nature in avian excreta, especially weathered pigeon droppings, which are believed to be the source of infection.

Mycosis: Cryptococcosis

Further reading:

Kreger-Van Rij, N.J.W. (ed) 1984. The Yeasts: a taxonomic study. 3rd Edition. Elsevier Science Publishers B.V., Amsterdam, The Netherlands.

Kwon-Chung, K.J. and J.E. Bennett. 1992. Medical Mycology. Lea & Febiger, Philadelphia and London.

Kwon-Chung K.J., Polacheck I., and Bennett J.E. 1982. Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (Serotypes A and D) and Cryptococcus neoformans var. gattii (Serotypes B and C). J. Clin. Microbiol. 15(3):535-537.