C. neoformans

WordNet

1. the 3rd letter of the Roman alphabet (同)c
2. (music) the keynote of the scale of C major
3. a general-purpose programing language closely associated with the UNIX operating system

PrepTutorEJDIC

1. carbonの化学記号
2. cesiumの化学記号
3. cadmiumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/31 19:11:17」(JST)

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Cryptococcus neoformans
Cryptococcus neoformans
Scientific classification
Kingdom:	Fungi
Phylum:	Basidiomycota
Class:	Tremellomycetes
Order:	Tremellales
Family:	Tremellaceae
Genus:	Cryptococcus
Species:	Cryptococcus neoformans
Binomial name
Cryptococcus neoformans (San Felice) Vuill.

Cryptococcus neoformans is an encapsulated yeast 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 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 gattii. C. neoformans v. grubii and v. neoformans have a worldwide distribution and are often found in soil that 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.

Characteristics

Cryptococcus neoformans stained by Gram stain

Cryptococcus neoformans grows as a yeast (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. 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 Cryptococcus 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.

Pathology

Infection with C. neoformans is termed cryptococcosis. Most infections with C. neoformans consist of a lung infection. 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. For this reason, C. neoformans is sometimes referred to as an opportunistic fungus. It is a facultative intracellular pathogen.

In human infection, C. neoformans is spread by inhalation of aerosolized spores (basidiospores) and can disseminate to the central nervous system where it can cause meningoencephalitis. In the lungs, C. neoformans are phagocytosed by alveolar macrophages Macrophages produce oxidative and nitrosative agents, creating a hostile environment, to kill invading pathogens. However, some C. neoformans 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 up-regulation 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 C. neoformans passes 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.

Meiosis (sexual reproduction), another possible survival factor for intracellular C. neoformans

The vast majority of environmental and clinical isolates of C. neoformans are mating type a. Filaments of mating type an ordinarily have haploid nuclei, but these can undergo a process of diploidization (perhaps by endoduplication or stimulated nuclear fusion) to form diploid cells termed blastospores. The diploid nuclei of blastospores are able to undergo meiosis, including recombination, to form haploid basidiospores that can then be dispersed. This process is referred to as monokaryotic fruiting. Required for this process is a gene designated dmc1, a conserved homologue of genes recA in bacteria, and rad51 in eukaryotes (see articles recA and rad51). Dmc1 mediates homologous chromosome pairing during meiosis and repair of double-strand breaks in DNA. (Also see article Meiosis.) Lin et al. suggested that one benefit of meiosis in C. neoformans could be to promote DNA repair in the DNA-damaging environment caused by the oxidative and nitrosative agents produced in macrophages. Thus, C. neoformans can undergo a meiotic process, monokaryotic fruiting, that may promote recombinational repair in the oxidative, DNA-damaging environment of the host macrophage, and this may contribute to its virulence.

Treatment

Cryptococcus neoformans seen in the lung of a patient with AIDS. The inner capsule of the organism stains red in this photomicrograph

Cryptococcosis that does not affect the central nervous system can be treated with fluconazole alone.

Cryptococcal meningitis should be treated for two weeks with intrathecal 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 400–800 mg daily for ten weeks and then 200 mg daily for at least one year and until the patient's CD4 count is above 200 cells/mcL. Flucytosine is a generic, off-patent medicine. However, there has been a market failure with a two-week cost of flucytosine therapy being approximately $10,000. As a result, flucytosine is currently universally unavailable in low- and middle-income countries. In 1970, flucytosine was available in Africa.

Intravenous Ambisome 4 (mg/kg)/day may be used but is not superior: Its main use is in patients that do not tolerate Amphotericin B. The dose of 200 mg/kg/day 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 often 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 not having taken fluconazole for many months. An increased dose of 400 mg daily does not improve outcomes, but prospective studies from Uganda and Malawi reported that higher doses of 1200 mg per day have more fungicidal activity. The outcomes with fluconazole monotherapy have 30% worse survival than amphotericin-based therapies, in a recent systematic review.

References

External links

• A good overview of Cryptococcus neoformans biology from the Science Creative Quarterly
• Cryptococcus neoformans biology, general information, life cycle image at MetaPathogen
• The outcome of Cryptococcus neoformans intracellular pathogenesis in human monocytes

UpToDate Contents

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• 1. 中枢神経系以外のクリプトコッカス-ネオフォルマン感染症 cryptococcus neoformans infection outside the central nervous system
• 2. クリプトコッカス-ネオフォルマン感染症の微生物学および疫学 microbiology and epidemiology of cryptococcus neoformans infection
• 3. HIV血清陰性患者におけるクリプトコッカス-ネオフォルマン髄膜脳炎および播種性感染症の治療 treatment of cryptococcus neoformans meningoencephalitis and disseminated infection in hiv seronegative patients
• 4. HIV感染患者におけるクリプトコッカス-ネオフォルマン髄膜脳炎の疫学、臨床症状、および診断 epidemiology clinical manifestations and diagnosis of cryptococcus neoformans meningoencephalitis in hiv infected patients
• 5. クリプトコッカス・ガッティ感染症：臨床的特徴および診断 cryptococcus gattii infection clinical features and diagnosis

English Journal

• pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies.

• Cornet M1, Gaillardin C.Author information 1Laboratoire TIMC-IMAG-TheREx, UMR 5525 CNRS-UJF, Université Joseph Fourier, Grenoble, France.AbstractFungi are exposed to broadly fluctuating environmental conditions, to which adaptation is crucial for their survival. An ability to respond to a wide pH range, in particular, allows them to cope with rapid changes in their extracellular settings. PacC/Rim signaling elicits the primary pH response in both model and pathogenic fungi and has been studied in multiple fungal species. In the predominant human pathogenic fungi, namely, Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, this pathway is required for many functions associated with pathogenesis and virulence. Aspects of this pathway are fungus specific and do not exist in mammalian cells. In this review, we highlight recent advances in our understanding of PacC/Rim-mediated functions and discuss the growing interest in this cascade and its factors as potential drug targets for antifungal strategies. We focus on both conserved and distinctive features in model and pathogenic fungi, highlighting the specificities of PacC/Rim signaling in C. albicans, A. fumigatus, and C. neoformans. We consider the role of this pathway in fungal virulence, including modulation of the host immune response. Finally, as now recognized for other signaling cascades, we highlight the role of pH in adaptation to antifungal drug pressure. By acting on the PacC/Rim pathway, it may therefore be possible (i) to ensure fungal specificity and to limit the side effects of drugs, (ii) to ensure broad-spectrum efficacy, (iii) to attenuate fungal virulence, (iv) to obtain additive or synergistic effects with existing antifungal drugs through tolerance inhibition, and (v) to slow the emergence of resistant mutants.
• Eukaryotic cell.Eukaryot Cell.2014 Mar;13(3):342-52. doi: 10.1128/EC.00313-13. Epub 2014 Jan 17.
• Fungi are exposed to broadly fluctuating environmental conditions, to which adaptation is crucial for their survival. An ability to respond to a wide pH range, in particular, allows them to cope with rapid changes in their extracellular settings. PacC/Rim signaling elicits the primary pH response in
• PMID 24442891

• Interleukin-17A Enhances Host Defense against Cryptococcal Lung Infection through Effects Mediated by Leukocyte Recruitment, Activation, and Gamma Interferon Production.

• Murdock BJ1, Huffnagle GB, Olszewski MA, Osterholzer JJ.Author information 1Pulmonary Section, VA Ann Arbor Healthcare System, Michigan, USA.AbstractInfection of C57BL/6 mice with the moderately virulent Cryptococcus neoformans strain 52D models the complex adaptive immune response observed in HIV-negative patients with persistent fungal lung infections. In this model, Th1 and Th2 responses evolve over time, yet the contribution of interleukin-17A (IL-17A) to antifungal host defense is unknown. In this study, we show that fungal lung infection promoted an increase in Th17 T cells that persisted to 8 weeks postinfection. Our comparison of fungal lung infection in wild-type mice and IL-17A-deficient mice (IL-17A(-/-) mice; C57BL/6 genetic background) demonstrated that late fungal clearance was impaired in the absence of IL-17A. This finding was associated with reduced intracellular containment of the organism within lung macrophages and deficits in the accumulation of total lung leukocytes, including specific reductions in CD11c(+) CD11b(+) myeloid cells (dendritic cells and exudate macrophages), B cells, and CD8(+) T cells, and a nonsignificant trend in the reduction of lung neutrophils. Although IL-17A did not alter the total number of CD4 T cells, decreases in the total number of CD4 T cells and CD8 T cells expressing gamma interferon (IFN-γ) were observed in IL-17A(-/-) mice. Lastly, expression of major histocompatibility complex class II (MHC-II) and the costimulatory molecules CD80 and CD86 on CD11c(+) CD11b(+) myeloid cells was diminished in IL-17A(-/-) mice. Collectively, these data indicate that IL-17A enhances host defenses against a moderately virulent strain of C. neoformans through effects on leukocyte recruitment, IFN-γ production by CD4 and CD8 T cells, and the activation of lung myeloid cells.
• Infection and immunity.Infect Immun.2014 Mar;82(3):937-48. doi: 10.1128/IAI.01477-13. Epub 2013 Dec 9.
• Infection of C57BL/6 mice with the moderately virulent Cryptococcus neoformans strain 52D models the complex adaptive immune response observed in HIV-negative patients with persistent fungal lung infections. In this model, Th1 and Th2 responses evolve over time, yet the contribution of interleukin-1
• PMID 24324191

Japanese Journal

• 教育シリーズ : Deep-seated mycosis : Cryptococcosis

• 掛屋 弘,河野 茂
• Medical mycology journal 52(3), 183-191, 2011
• NAID 40019063649

• 教育シリーズ : Basic mycology クリプトコックスのリン酸代謝制御系

• 東江 昭夫,清水 公徳,Li Hao-Man [他]
• Medical mycology journal 52(1), 19-23, 2011
• NAID 40019063635

Related Links

• C.neoformans 1 - トップ｜群馬県臨床検査技師会

【はじめに】Cryptococcus neoformans （以下 C.neoformans）は、土壌中に存在する真菌で、鳥類とくに ハトの糞中に高率に存在する。ヒトに対する病原性は弱いが、 肺や中枢神経に感染し、中枢神経に感染した場合は死亡する 症例も ...

• C. neoformans Infection | Fungal Diseases | CDC

Cryptococcus neoformans is a fungus that lives in the environment throughout the world. People can become infected with C. neoformans after breathing in the microscopic fungus, although most people who are exposed to the fungus ...

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★リンクテーブル★

リンク元	「Cryptococcus neoformans」
関連記事	「C」「Cs」「Cd」「neoformans」「c」

「Cryptococcus neoformans」

　　[★]

ラ

Cryptococcus neoformans, C. neoformans

同

Filobasidiella neoformans、クリプトコッカス・ネオフォルマンス

関

クリプトコッカス症

• 厚い莢膜
• 不完全菌酵母
• 担子菌
• 感染組織内、培地でも莢膜を持つ単細胞(酵母)として増殖
• 中枢神経系に強い親和性を有する。

分布

• ミルク、加重、健常者の皮膚、消化管
• 土壌特にハトその他の鳥類、コアラの糞などで汚染された土壌に豊富に存在

染色

• 墨汁染色

感染症

• クリプトコッカス症(肺クリプトコッカス症、クリプトコッカス髄膜炎、播種性クリプトコッカス症)

感染経路は空気感染　→　肺クリプトコッカス症

細胞免疫能低下患者　→　髄膜や脳に二次感染

HIV患者では高頻度にクリプトコッカス髄膜炎

参考

• 真菌の写真 - Fungal Images

• http://www.asm.org/Division/c/fungi.htm

「C」

　　[★]

• 炭素 carbon
• シトシン cytosine
• システイン cysteine
• シチジン
• セルシウス度 摂氏 degrees Celsius degree C
• 産婦人科領域で「子宮外頚 子宮外頚部 exocervix」を表現するための略語

　 　 　 　

「Cs」

　　[★] セシウム, caesium, cesium 　

「Cd」

　　[★] カドミウム

関

cadmium

　

「neoformans」

　　[★]

• Cryptococcus neoformans

「c」

　　[★]

• 光速, speed of light