Cryptococcus gattii

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Classification

"Cryptococcus gattii"

Eukaryota; Fungi; Basidiomycota; Tremellomycetes; Tremellales; Cryptococcaceae; Cryptococcus [1].

Introduction

Cryptococcus gattii is a fungal pathogen originating in Australian eucalyptus and almond trees [2]. that has been known to cause respiratory failure and serious central nervous system complications when infecting a human host [3]. Although the pathogenicity of C. gattii has in large part already been investigated, the global distribution of the microbe is unclear because strains of the fungus have only been found in places where samples are tested - areas of high-incidence [4]. This yeast is endemic in parts of Australia, and is normally found in tropical and subtropical areas. However, it has recently been identified as the cause of a cryptococcosis outbreak in British Columbia and parts of the American Pacific Northwest [2]. C. gattii is a leading cause of pulmonary cryptococcosis, basal meningitis, and cerebral cryptococcomas whose emergence, it has been suggested, is a result of changing climate conditions [5].

Genome structure

C. gattii has four main genetic groups (VGI, VGII, VGIII, VGIV); each of these genetic groups has 14 distinct chromosomes. Among these four genetic groups, the majority of genes are collinear, meaning that the same genes are found in the same locations on each of the chromosomes [2]. Amongst these four main groups, there is no evidence of any nuclear exchange. This is indicative of three separate but related species [6]. Sequencing of the mitochondrial genomes of VGI and VGII show adequate sequence similarity to suggest uniparental mitochondrial inheritance, but evidence of virulent traits between these distinct species in laboratory settings indicates that the transfer of mitochondrial genomes between species is possible [6]. 58 different genes located on 68 loci have been identified as showing divergent patterns of copy number variation amongst these 4 genetic groups [7]. The genome contains the CAP59 gene, which encodes the polysaccharide capsule, the LAC1 gene, which is involved in melanin synthesis, and the PLB1 gene, which encodes proteins that allow the yeast to invade host cells, among other proteins [2].

Cell structure

The cell diameter of most C. gattii cells typically ranges from 3-5 micrometers [3]. Most cells are roughly circular in shape, although it is capable of changing the size and shape of its capsule to avoid an immune response. C. gattii has a polysaccharide capsule, which is its main virulence factor [3]. C. gattii is typically found in the yeast form. It typically reproduces through asexual budding in both the environment and inside human hosts once an infection has occurred [2]. It is possible for sexual reproduction to occur. Cells can also undergo a dimorphic transition to hyphae to create a mycelium and generate basidiospores [2].

Metabolic processes

Creatinine deiminase is expressed in C. gattii in presence of creatinine; unlike its close relative C. neoformans, this enzyme is not repressed by the presence of ammonia in iC. gattii [8]. Carbon sources include glycine and dicarboxylic acids. 94% of iC. gattii strains are able to use D-alanine as the sole source of nitrogen for the cell. However, very few strains are able to utilize L-phenylalanine and none of the strains are able to use L-tryptophan as a nitrogen source [8]. When cultured in vitro, C. gattii display a characteristic abundance of the disaccharide α,α-trehalose, which allows for easy identification of the fungal growth in vivo [2].

The presence of the enzyme laccase has been detected in many strains of C. gattii. Laccase is responsible for the production of several different molecules that are important to the virulence of the yeast [2]. First of all, laccase promotes the production of melanin, which aids in energy production via oxidative phosphorylation [2]. Laccase also promotes the production of phospholipase B and urease, both important enzymes for the invasion of host tissue during infection. Lastly, laccase is responsible for the production of two antioxidants, trehalose and superoxide dismutase [2].

Ecology

Originally, C. gattii was only found in tropical and subtropical areas, like Australia and Southern California [3]. However, it has recently been found elsewhere, including the Pacific Northwest of the United States and Vancouver, Canada [9]. The fungus’ preferred environment changes depending on where it is found, which is how it has been found to survive in both tropical and temperate locations. It has been isolated in many places, including soil and man-made objects, like tires [9]. It can also live in seawater or freshwater for up to a year [9]. Plant material can promote the yeast’s fertility and possibly make it more pathogenic. The yeast are normally confined to individual trees because it has limited dispersal [2].

Current Research

Current research on C. gattii has focused on understanding its pathology and where outbreaks are likely to occur. A recent study published by Costa et al. was the first to examine the link between the microbiota of the large intestine and the body’s immune response to C. gattii [3]. Germ-Free (GF) mice without a functioning microbiome had a decreased ability to combat the infection, while the conventional (CV), conventionalized (CVN), and LPS-stimulated mice with microbiomes all had a greater immune response to the infection which led to higher survival rates [3].

Recent research has also explored the effect that copy number variants (CNVs) have on genetic differences and increased virulence between strains [7]. CNVs contributed greatly to differences in transport, cell wall structure, and the capsule structure. All of these effects contributed to an increased virulence amongst C. gattii strains [7].

The CDC has been examining the occurrence and potential spread of C. gattii through the United States to predict where outbreaks may occur. Strains VGIIa, VGIIb, and VGIIc have been causing cryptococcosis infections in the Pacific Northwest, even though the U.S. was previously believed to be outside the normal climate range [10]. There was no clear route of introduction, but agricultural products were the most likely mode of transport. In past cases in North America, C. gattii has caused neurological problems such as seizures and headaches [10].

A recent CDC study determined that C. gattii is also endemic to regions in the Southeastern United States as well as the Pacific Northwest [13]. VGI and VGIII strains were found in the southeastern states and were found to have more single-nucleotide polymorphisms (SNP) than strains from the Pacific Northwest. Due to the increased diversity in the VGI and VGIII strains, it was concluded that the southeastern C. gattii strains are older than the northwestern strains [13].

Other

2000-2001 Outbreak: Between January 1999 and December 2001, an outbreak of cryptococcosis occurred in British Columbia [12]. Approximately 38 cases of human cryptococcosis were recorded; all were caused by C. gattii. 95.2% of these human cases were identified as the VGII strain, and the remaining case was identified as VGI [12]. All isolates from environmental samples were identified as the VGII strain, which was determined to have caused this outbreak in British Columbia. British Columbia and the Pacific Northwest are both new locations for this microbe; C. gattii was previously found only in tropical and subtropical locations [12].

References

It is required that you add at least five primary research articles (in same format as the sample reference below) that corresponds to the info that you added to this page. [Sample reference] Faller, A., and Schleifer, K. "Modified Oxidase and Benzidine Tests for Separation of Staphylococci from Micrococci". Journal of Clinical Microbiology. 1981. Volume 13. p. 1031-1035.

[1] Cryptococcus gattii VGI. Retrieved October 21st, 2016

[2] Chen, S. C., Meyer, W., & Sorrell, T. C. (2014). Cryptococcus gattii Infections. Clinical Microbiology Reviews 4: 980-1024.

[3] Costa, M. C., Santos, J. R., Ribeiro, M. J., Freitas, G. J., Bastos, R. W., Ferreira, G. F., . . . Santos, D. A. (2016). The absence of microbiota delays the inflammatory response to Cryptococcus gattii. International Journal of Medical Microbiology 306 (4): 187-195.

[4] Harris, J., Lockhart, S., & Chiller, T. (2011). Cryptococcus gattii: where do we go from here? Oxford Journals: Medical Mycology 50 (2): 113-129.