Cryptococcus neoformans ACBS527

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Eukaryota; Fungi; Basidiomycota; Tremellales; Cryptococcus [Others may be used. Use NCBI link to find]


NCBI: [1]

Cryptococcus neoformans

Description and Significance

Cryptococcus neoformans exists in the environment in both unicellular yeasts and multicellular hyphal forms. In the environment, it exists as a typical fungal yeast cell. However, C. neoformans is an opportunistic human pathogen, and when it has infected a human, it forms a polysaccharide membrane capsule around the yeast cell. Properties of the capsule allow for C. neoformans to evade host immune response [2].C. neoformans can exist as either of two mating types, a or α, with α being more common in environmental and clinical sample and also thought to be more virulent [3].

Life Cycle, Cell Structure, Metabolism

C. neoformans is a saprobic fungal species with the unusual feature of having a polysaccharide capsule when infecting the human body. The cell wall of C. neoformans contains melanin, which is thought to be a virulence factor [2]. It is most often found as yeast cells but has the ability to form pseudo-hyphae as well as a short-lived hyphal stage which exists solely for sexual reproduction [4].

Sexual Reproduction

C. neoformans exhibits a bipolar mating system with an a or α mating type locus (MAT) and can reproduce through bi- or unisexual reproduction. Bisexual reproduction occurs under very specific conditions such as low nitrogen and water levels. These conditions will allow for fungal cells of opposite mating types to fuse and form a dikaryotic hyphae. Hyphal growth exhibits the presence of clamp connections, distinct to basidiomycetes, and a basidium can form, allowing for karyogamy, meiosis, and the formation of haploid basidiospores [4]. In unisexual reproduction, only one mating type is necessary. Unisexual reproduction refers to monokaryotic, or haploid, fruiting. Haploid spores diploidize to hyphal cells, a basidia forms and meiosis occurs, forming more haploid spores [4]. It Is thought that unisexual reproduction occurs more frequently than bisexual reproduction, which accounts for the fact that MATα is found predominantly in the environment and clinical samples.

Asexual Reproduction

Asexual reproduction of C. neoformans can happen at any point in its life cycle. It mainly occurs by budding of yeast cells from other yeast cells, hyphae, or clamp connections directly after a mitotic event occurs [3].

Genome Structure

The genome of C. neoformans is approximately 20 MB and spans 14 chromosomes. There exist genes that are highly specific to C. neoformans involved in the formation of the polysaccharide capsule (CAP64). Overall, the genome has clusters of transposons around the centromeric regions of chromosomes, which are thought to drive phenotypic variation [3].

Ecology and Pathogenesis

The natural habitat of C. neoformans is pigeon droppings and contaminated soils. Therefore, it is found ubiquitously across the world [2]. C. neoformans is an opportunistic pathogen that infects immunocompromised individuals such as AIDS patients [2]. In fact, infection by C. neoformans causes the greatest amount of mycosis fatalities for AIDS patients than any other fungal species. C. neoformans is introduced to the body through formation of yeast cells and basidiospores in the environment and subsequent inhalation. Once inhaled, it has the potential to colonize the lungs. If the infection persists, it is able to spread to the central nervous system (CNS) [5]. Once the infection spreads to the CNS, it can cause meningocephalitis, which is 100% fatal if not treated [6].

In immunocompetent patients, invasion by C. neoformans is usually overcome without symptoms. However, in immunocompromised patients, the polysaccharide capsule allows for the evasion of immune response. Additionally, the cell wall of C. neoformans contains melanin, which is also thought to be an important virulence factor. Melanin is what aids in the escape of C. neoformans from the lungs and into the CNS. It also helps in survival of yeast cells, protecting it from reactive oxygen species as well as anti-fungal agents. Once C. neoformans reaches the CNS, it attaches to human brain microvascular endothelial cells, allowing it to cross the blood-brain barrier [7]. The mechanism of how the fungal cells attach is at this time unclear.

Symptoms of lung infection include [8]:

  • Cough
  • Shortness of breath
  • Chest pain
  • Fever

Symptoms of CNS infection include [8]:

  • Headache
  • Fever
  • Neck pain
  • Nausea/vomiting
  • Confusion/changes in behavior

Diagnosis of 'C. neoformans' infection includes various laboratory tests including antigen testing and culturing of blood, cerebrospinal fluid, or sputum samples from the patient [9]. Several anti-fungal treatments exist to treat infection. Fluconazole is used to treat mild lung infection, whereas a combination of amphotericin B and flucytosine are used to treat severe lunch infection and CNS infection [10].

Currently, infection by C. neoformans have become less prevalent in developed countries due to the availability of antiretroviral therapy drugs for HIV patients. However, in developing countries where HIV/AIDS is still highly prevalent, such as sub-Saharan Africa, C. neoformans infection is still a problem. There are over 162,000 cases of Cryptococcol meningitis in sub-Saharan Africa compared to 9,700 cases in North and South America combined [11].


[2] Olszewski, M. A., Zhang, Y., & Huffnagle, G. B. (2010). Mechanisms of cryptococcal virulence and persistence. Future Microbiology, 5(8), 1269–1288.

[3] Loftus, B. J., Fung, E., Roncaglia, P., Rowley, D., Amedeo, P., Bruno, D., … Hyman, R. W. (2005). The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science, 307(5713), 1321–1324.

[4] Zhao, Y., Lin, J., Fan, Y., & Lin, X. (2019). Life Cycle of Cryptococcus neoformans . Annual Review of Microbiology, 73(1), 17–42.

[5] Karkowska-Kuleta, J., Rapala-Kozik, M., & Kozik, A. (2009). Fungi pathogenic to humans: Molecular bases of virulence of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Acta Biochimica Polonica, 56(2), 211–224.

[6] Karkowska-Kuleta, J., Rapala-Kozik, M., & Kozik, A. (2009). Fungi pathogenic to humans: Molecular bases of virulence of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Acta Biochimica Polonica, 56(2), 211–224.

[7] Chang, Y. C., Stins, M. F., McCaffery, M. J., Miller, G. F., Pare, D. R., Dam, T., … Kwon-Chung, K. J. (2004). Erratum: Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier (Infection and Immunity (2004) 72, 9 (4985-4995)). Infection and Immunity, 72(11), 6753.

[8] CDC. (2018). Fungal Diseases: Symptoms. Centers for Disease Control and Prevention.

[9] CDC. (2018). Fungal Diseases: Diagnosis and Testing. Centers for Disease Control and Prevention.

[10] CDC. (2018). Fungal Diseases: Treatment & Outcomes. Centers for Disease Control and Prevention.

[11] CDC. (2018). Fungal Diseases: Statistics. Centers for Disease Control and Prevention.


Page authored by Christina Morrison, student of Dr. Marc Orbach, University of Arizona .