Cryptococcus neoformans
Encyclopedia
Cryptococcus neoformans is an encapsulated yeast
that can live in both plant
s and animal
s. Its teleomorph is Filobasidiella neoformans, a filamentous fungus
belonging to the class
Tremellomycetes
. It is often found in pigeon excrement.
. C. neoformans v. grubii and v. neoformans have a worldwide distribution and are often found in soil which has been contaminated by bird excrement. The genome sequence of C. neoformans v. neoformans was published in 2005. Recent studies suggest that colonies of Cryptococcus neoformans and related fungi growing on the ruins of the melted down
reactor of the Chernobyl Nuclear Power Plant
may be able to use the energy of radiation
(primary beta radiation) for "radiotrophic
" growth.
(unicellular) and replicates by budding
. C. neoformans makes hyphae during mating, and eventually creates basidiospores at the end of the hyphae before producing spores. Under host-relevant conditions, including low glucose, serum, 5% carbon dioxide, and low iron, among others, the cells produce a characteristic polysaccharide capsule.
When grown as a yeast, C. neoformans has a prominent capsule composed mostly of polysaccharides. Microscopically, the India ink
stain is used for easy visualization of the capsule. The particles of ink pigment do not enter the capsule that surrounds the spherical yeast cell, resulting in a zone of clearance or "halo" around the cells. This allows for quick and easy identification of C. neoformans.
C. neoformans grows rapidly on exposure to radiation such as gamma-radiation. Radiation seems to increase the electron-transfer capability of melanin in the fungus, increasing its total metabolic activity.
. Most infections with C. neoformans consist of a lung infection. However, fungal meningitis
, especially as a secondary infection for AIDS
patients, is often caused by C. neoformans making it a particularly dangerous fungus. Infections with this fungus are rare in those with fully functioning immune systems. For this reason, C. neoformans is sometimes referred to as an opportunistic fungus. It is a facultative intracellular pathogen.
alone.
Cryptococcal meningitis should be treated for two weeks with intravenous Amphotericin B
0.7–1.0 (mg/kg)/day and oral flucytosine
100 (mg/kg)/day (or intravenous flucytosine 75 (mg/kg)/day if the patient is unable to swallow). This should then be followed by oral fluconazole 200 mg daily for ten weeks and then 200 mg daily until the patient's CD4
count is above 100 for three months and, if infected, his HIV viral load
is undetectable.
Intravenous Ambisome 4 (mg/kg)/day may be used but is not superior: its main use is in patients who do not tolerate Amphotericin B. The 200 (mg/kg)/day dose for flucytosine is not more effective, is associated with more side-effects and should not be used.
In Africa, oral fluconazole at a rate of 200 mg daily is used. However, this does not result in cure because it merely suppresses the fungus and does not kill it; viable fungus can continue to be grown from CSF
of patients who have taken fluconazole for many months. An increased dose of 400 mg daily does not improve outcomes, but preliminary data from Uganda
shows that very high doses of 1200 mg or more per day may be effective. The duration of this treatment and the post-treatment maintenance dose is not known.
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
that can live in both plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s and animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s. Its teleomorph is Filobasidiella neoformans, a filamentous fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
belonging to the class
Class (biology)
In biological classification, class is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, order, family, genus, and species, with class fitting between phylum and order...
Tremellomycetes
Tremellomycetes
The Tremellomycetes are a class of dimorphic fungi. Some species have a gelatinous fruiting body or a sacculate parenthesome. There are 3 orders, 11 families, 50 genera, and 377 species in the Tremellomycetes....
. It is often found in pigeon excrement.
Classification
Cryptococcus neoformans is composed of two varieties (v.): C. neoformans v. neoformans and v. grubii. A third variety, C. neoformans v. gattii, is now considered a distinct species, Cryptococcus gattiiCryptococcus gattii
Cryptococcus gattii, formerly known as Cryptococcus neoformans var gattii, is an encapsulated yeast found primarily in tropical and subtropical climates...
. C. neoformans v. grubii and v. neoformans have a worldwide distribution and are often found in soil which has been contaminated by bird excrement. The genome sequence of C. neoformans v. neoformans was published in 2005. Recent studies suggest that colonies of Cryptococcus neoformans and related fungi growing on the ruins of the melted down
Nuclear meltdown
Nuclear meltdown is an informal term for a severe nuclear reactor accident that results in core damage from overheating. The term is not officially defined by the International Atomic Energy Agency or by the U.S. Nuclear Regulatory Commission...
reactor of the Chernobyl Nuclear Power Plant
Chernobyl Nuclear Power Plant
The Chernobyl Nuclear Power Plant or Chornobyl Nuclear Power Plant is a decommissioned nuclear power station near the city of Pripyat, Ukraine, northwest of the city of Chernobyl, from the Ukraine–Belarus border, and about north of Kiev. Reactor 4 was the site of the Chernobyl disaster in...
may be able to use the energy of radiation
Particle radiation
Particle radiation is the radiation of energy by means of fast-moving subatomic particles. Particle radiation is referred to as a particle beam if the particles are all moving in the same direction, similar to a light beam....
(primary beta radiation) for "radiotrophic
Radiotrophic fungus
Radiotrophic fungi are fungi which appear to use the pigment melanin to convert gamma radiation into chemical energy for growth. This proposed mechanism may be similar to anabolic pathways for the synthesis of reduced organic carbon in phototrophic organisms, which capture photons from visible...
" growth.
Characteristics
Cryptococcus neoformans grows as a yeastYeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
(unicellular) and replicates by budding
Budding
Budding is a form of asexual reproduction in which a new organism grows on another one. The new organism remains attached as it grows, separating from the parent organism only when it is mature. Since the reproduction is asexual, the newly created organism is a clone and is genetically identical...
. C. neoformans makes hyphae during mating, and eventually creates basidiospores at the end of the hyphae before producing spores. Under host-relevant conditions, including low glucose, serum, 5% carbon dioxide, and low iron, among others, the cells produce a characteristic polysaccharide capsule.
When grown as a yeast, C. neoformans has a prominent capsule composed mostly of polysaccharides. Microscopically, the India ink
India ink
India ink is a simple black ink once widely used for writing and printing and now more commonly used for drawing, especially when inking comic books and comic strips.-Composition:...
stain is used for easy visualization of the capsule. The particles of ink pigment do not enter the capsule that surrounds the spherical yeast cell, resulting in a zone of clearance or "halo" around the cells. This allows for quick and easy identification of C. neoformans.
Pathology
Infection with C. neoformans is termed cryptococcosisCryptococcosis
Cryptococcosis, or cryptococcal disease, is a potentially fatal fungal disease. It is caused by one of two species; Cryptococcus neoformans and Cryptococcus gattii. These were all previously thought to be subspecies of C...
. Most infections with C. neoformans consist of a lung infection. However, fungal meningitis
Fungal meningitis
Fungal meningitis refers to meningitis caused by a fungal infection.One form of fungal meningitis is cryptococcal meningitis.Many cases of fungal meningitis are associated with immune deficiencies....
, especially as a secondary infection for AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients, is often caused by C. neoformans making it a particularly dangerous fungus. Infections with this fungus are rare in those with fully functioning immune systems. For this reason, C. neoformans is sometimes referred to as an opportunistic fungus. It is a facultative intracellular pathogen.
Treatment
Cryptococcosis that does not affect the central nervous system can be treated with fluconazoleFluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
alone.
Cryptococcal meningitis should be treated for two weeks with intravenous Amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
0.7–1.0 (mg/kg)/day and oral flucytosine
Flucytosine
Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug.It is structurally related to the cytostatic fluorouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon. Flucytosine was...
100 (mg/kg)/day (or intravenous flucytosine 75 (mg/kg)/day if the patient is unable to swallow). This should then be followed by oral fluconazole 200 mg daily for ten weeks and then 200 mg daily until the patient's CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
count is above 100 for three months and, if infected, his HIV viral load
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
is undetectable.
Intravenous Ambisome 4 (mg/kg)/day may be used but is not superior: its main use is in patients who do not tolerate Amphotericin B. The 200 (mg/kg)/day dose for flucytosine is not more effective, is associated with more side-effects and should not be used.
In Africa, oral fluconazole at a rate of 200 mg daily is used. However, this does not result in cure because it merely suppresses the fungus and does not kill it; viable fungus can continue to be grown from CSF
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
of patients who have taken fluconazole for many months. An increased dose of 400 mg daily does not improve outcomes, but preliminary data from Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
shows that very high doses of 1200 mg or more per day may be effective. The duration of this treatment and the post-treatment maintenance dose is not known.