Cryptococcus neoformans

Cryptococcus neoformans is an encapsulated yeast and an obligate aerobe that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in bird excrement. Cryptococcus neoformans is an encapsulated fungal organism and it can cause disease in apparently immunocompetent, as well as immunocompromised, hosts. Cryptococcus neoformans has undergone numerous nomenclature revisions since its first description in 1894. For instance, it once contained two varieties (var.): C. neoformans var. neoformans and C. neoformans var. grubii. A third variety, C. neoformans var. gattii, was defined as a distinct species, Cryptococcus gattii. The most recent classification system divides organisms into seven species. C. neoformans refers to C. neoformans var. grubii. A new species name, Cryptococcus deneoformans, is used for the former C. neoformans var. neoformans. C. gattii is divided into five species. C. neoformans grows as a yeast (unicellular) and replicates by budding. It 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. The recognition of C. neoformans in Gram-stained smears of purulent exudates may be hampered by the presence of the large gelatinous capsule which apparently prevents definitive staining of the yeast-like cells. In such stained preparations, it may appear either as round cells with Gram-positive granular inclusions impressed upon a pale lavender cytoplasmic background or as Gram-negative lipoid bodies.When grown as a yeast, C. neoformans has a prominent capsule composed mostly of polysaccharides. Under the microscope, the India ink stain is used for easy visualization of the capsule in cerebral spinal fluid. 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. Unusual morphological forms are rarely seen. For identification in tissue, mucicarmine stain provides specific staining of polysaccharide cell wall in C. neoformans. Cryptococcal antigen from cerebrospinal fluid is thought to be the best test for diagnosis of cryptococcal meningitis in terms of sensitivity, though it might be unreliable in HIV-positive patients. The first genome sequence for a strain of C. neoformans (var. neoformans; now C. deneoformans) was published in 2005. Studies suggest that colonies of C. 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 for 'radiotrophic' growth. Infection with C. neoformans is termed cryptococcosis. Most infections with C. neoformans occur in the lungs. However, fungal meningitis and encephalitis, especially as a secondary infection for AIDS patients, are often caused by C. neoformans, making it a particularly dangerous fungus. Infections with this fungus are rare in those with fully functioning immune systems. So, C. neoformans is sometimes referred to as an opportunistic fungus. It is a facultative intracellular pathogen that can utilize host phagocytes to spread within the body. Cryptococcus neoformans was the first intracellular pathogen for which the non-lytic escape process termed vomocytosis was observed. It has been speculated that this ability to manipulate host cells results from environmental selective pressure by amoebae, a hypothesis first proposed by Arturo Casadevall under the term 'accidental virulence'. In human infection, C. neoformans is spread by inhalation of aerosolized basidiospores, and can disseminate to the central nervous system, where it can cause meningoencephalitis. In the lungs, C. neoformans cells are phagocytosed by alveolar macrophages. Macrophages produce oxidative and nitrosative agents, creating a hostile environment, to kill invading pathogens. However, some C. neoformans cells can survive intracellularly in macrophages. Intracellular survival appears to be the basis for latency, disseminated disease, and resistance to eradication by antifungal agents. One mechanism by which C. neoformans survives the hostile intracellular environment of the macrophage involves upregulation of expression of genes involved in responses to oxidative stress. Traversal of the blood–brain barrier by C. neoformans plays a key role in meningitis pathogenesis. However, precise mechanisms by which it passes the blood-brain barrier are still unknown; one recent study in rats suggested an important role of secreted serine proteases. The metalloprotease Mpr1 has been demonstrated to be critical in blood-brain barrier penetration.