Xin-miao JIA, Meng XIAO, Tian-shu SUN, Ying-chun XU. Advances in Genomic Research of Cryptococcus Gattii[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(5): 505-513. doi: 10.3969/j.issn.1674-9081.2019.05.014
Citation: Xin-miao JIA, Meng XIAO, Tian-shu SUN, Ying-chun XU. Advances in Genomic Research of Cryptococcus Gattii[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(5): 505-513. doi: 10.3969/j.issn.1674-9081.2019.05.014

Advances in Genomic Research of Cryptococcus Gattii

doi: 10.3969/j.issn.1674-9081.2019.05.014
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  • Corresponding author: XU Ying-chun Tel: 86-10-69159766,
  • Received Date: 2019-03-14
  • Publish Date: 2019-09-30
  • Cyptococcus gattii(C.gattii) belongs to the Cryptococcus neoformans complex and was previously considered to be a variant of the Cryptococcus neoformans complex (C. neoformans var. gattii) but eventually established as a separate species. Unlike C. neoformans, C. gattii predominantly infects immunocompetent persons. The pathogenic mechanism of C. gattii is not yet clear. The genomic research of C. gattii can not only comprehensively characterize the genetic composition, molecular evolution, virulence factors and pathogenic mechanisms, but also be used for the prediction of pathogenic genes and important proteins, which further facilitates the development of vaccines and new antibiotics and the construction of new effective treatments and prevention strategies against cryptococcosis. In this paper, the whole genome sequencing, genome features, genomic evolution, important virulence factors, and comparative genomic researches are reviewed.
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  • [1] Kwon-Chung KJ, Varma A. Do major species concepts support one, two or more species within Cryptococcus neoformans?[J]. FEMS Yeast Res, 2006, 6:574-587. doi:  10.1111/j.1567-1364.2006.00088.x
    [2] Chen SCA, Meyer W, Sorrell TC. Cryptococcus gattii Infections[J]. Clin Microbiol Rev, 2014, 27:980-1024. doi:  10.1128/CMR.00126-13
    [3] Chen CH, Wang SH, Chen WL, et al. Ocular complications caused by Cryptococcus gattii AFLP4/VGI meningitis in an immunocompetent host[J]. Rev Inst Med Trop Sao Paulo, 2016, 58:85.
    [4] Meyer W. Cryptococcus gattii in the age of whole-genome sequencing[J]. Mbio, 2015, 6:e01761-15.
    [5] Bovers M, Hagen F, Kuramae EE, et al. Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multi-locus sequence typing[J]. Fungal Genet Biol, 2008, 45:400-421. doi:  10.1016/j.fgb.2007.12.004
    [6] Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada)[J]. Proc Natl Acad Sci U S A, 2004, 101:17258-17263. doi:  10.1073/pnas.0402981101
    [7] Meyer W, Castaneda A, Jackson S, et al. Molecular typing of IberoAmerican Cryptococcus neoformans isolates[J]. Emerg Infect Dis, 2003, 9:189-195. doi:  10.3201/eid0902.020246
    [8] Trilles L, Lazera M, Wanke B, et al.Genetic characterization of environmental isolates of the Cryptococcus neoformans species complex from Brazil[J]. Med Mycol, 2003, 41:383-390. doi:  10.1080/1369378031000137206
    [9] Trilles L, Lazera Mdos S, Wanke B, et al. Regional pattern of the molecular types of Cryptococcus neoformans and Cryptococcus gattii in Brazil[J]. Mem I Oswaldo Cruz, 2008, 103:455-462. doi:  10.1590/S0074-02762008000500008
    [10] Harris JR, Lockhart SR, Debess E, et al. Cryptococcus gattii in the United States:clinical aspects of infection with an emerging pathogen[J]. Clinl Infect Dis, 2011, 53:1188-1195. doi:  10.1093/cid/cir723
    [11] 窦红涛, 万喆, 杨启文, 等.格特隐球菌在河北地区引起1例脑膜炎的临床与实验研究[J].中国真菌学杂志, 2015, 10:11-15.
    [12] 金亮, 沈定霞.格特隐球菌感染的临床特征与实验室研究进展[J].检验医学, 2017, 32:1065-1069.
    [13] 葛瑛, 张凯宇, 马小军, 等.隐球菌脑膜炎62例临床分析[J].协和医学杂志, 2018, 9:431-436.
    [14] Velez N, Escandon P. Report on novel environmental niches for Cryptococcus neoformans and Cryptococcus gattii in Colombia:Tabebuia guayacan and Roystonea regia[J]. Med Mycol, 2017, 55:794-797.
    [15] D'Souza CA, Kronstad JW, Taylor G, et al. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts[J]. Mbio, 2011, 2:e00342-10.
    [16] Bovers M, Hagen F, Kuramae EE, et al. Promiscuous mitochondria in Cryptococcus gattii[J]. FEMS Yeast Res, 2009, 9:489-503. doi:  10.1111/j.1567-1364.2009.00494.x
    [17] Ngamskulrungroj P, Gilgado F, Faganello J, et al. Genetic diversity of the Cryptococcus species complex suggests that Cryptococcus gattii deserves to have varieties[J]. PLoS One, 2009, 4:e5862. doi:  10.1371/journal.pone.0005862
    [18] Xu J, Vilgalys R, Mitchell TG. Multiple gene genealogies reveal recent dispersion and hybridization in the human pathogenic fungus Cryptococcus neoformans[J]. Mol Ecol, 2000, 9:1471-1481. doi:  10.1046/j.1365-294x.2000.01021.x
    [19] Gonzalez GM, Casillas-Vega N, Garza-Gonzalez E, et al. Molecular typing of clinical isolates of Cryptococcus neoformans/Cryptococcus gattii species complex from Northeast Mexico[J]. Folia Microbiol, 2016, 61:51-56. doi:  10.1007/s12223-015-0409-8
    [20] Gillece JD, Schupp JM, Balajee SA, et al. Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity[J]. PLoS One, 2011, 6:e28550. doi:  10.1371/journal.pone.0028550
    [21] Hagen F, Ceresini PC, Polacheck I, et al. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest[J]. PLoS One, 2013, 8:e71148. doi:  10.1371/journal.pone.0071148
    [22] Engelthaler DM, Hicks ND, Gillece JD, et al. Cryptococcus gattii in North American Pacific Northwest:Whole-popula-tion genome analysis provides insights into species evolution and dispersal[J]. Mbio, 2014, 5:e01464-14.
    [23] Billmyre RB, Croll D, Li WJ, et al. Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution[J]. Mbio, 2014, 5:e01494-14.
    [24] Byrnes EJ, Bildfell RJ, Frank SA, et al. Molecular evidence that the range of the Vancouver Island out-break of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States[J]. J Infect Dis, 2009, 199:1081-1086. doi:  10.1086/597306
    [25] Hagen F, Colom MF, Swinne D, et al. Autochthonous and dormant Cryptococcus gattii infections in Europe[J]. Emerg Infect Dis, 2012, 18:1618-1624. doi:  10.3201/eid1810.120068
    [26] Steele KT, Thakur R, Nthobatsang R, et al. In-hospital mortality of HIV-infected cryptococcal meningitis patients with C. gattii and C. neoformans infection in Gaborone, Botswana[J]. Med Mycol, 2010, 48:1112-1115. doi:  10.3109/13693781003774689
    [27] Carriconde F, Gilgado F, Arthur I, et al. Clonality and alpha-a recombination in the Australian Cryptococcus gattii VGII population-an emerging outbreak in Australia[J]. PLoS One, 2011, 6:e16936. doi:  10.1371/journal.pone.0016936
    [28] Kronstad JW, Attarian R, Cadieux B, et al. Expanding fungal pathogenesis:Cryptococcus breaks out of the opportunistic box[J]. Nat Rev Microbiol, 2011, 9:193-203. doi:  10.1038/nrmicro2522
    [29] Ma H, May RC. Virulence in Cryptococcus species[J]. Adv Appl Microbiol, 2009, 67:131-190. doi:  10.1016/S0065-2164(08)01005-8
    [30] Kozel TR, Gotschlich EC. The capsule of Cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages[J]. J Immunol, 1982, 129:1675-1680.
    [31] Tucker SC, Casadevall A. Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm[J]. Proc Natl Acad Sci U S A, 2002, 99:3165-3170. doi:  10.1073/pnas.052702799
    [32] Feldmesser M, Kress Y, Novikoff P, et al.Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection[J]. Infect Immun, 2000, 68:4225-4237. doi:  10.1128/IAI.68.7.4225-4237.2000
    [33] Casadevall A, Rosas AL, Nosanchuk JD. Melanin and virulence in Cryptococcus neoformans[J]. Curr Opin Microbiol, 2000, 3:354-358. doi:  10.1016/S1369-5274(00)00103-X
    [34] Williamson PR. Laccase and melanin in the pathogenesis of Cryptococcus neoformans[J]. Frontiers Biosci, 1997, 2:e99-e107. doi:  10.2741/A231
    [35] van Duin D, Casadevall A, Nosanchuk JD. Melanization of Cryptococcus neoformans and histoplasma capsulatum reduces their susceptibilities to amphotericin B and caspofungin[J]. Antimicrob Agents Ch, 2002, 46:3394-3400. doi:  10.1128/AAC.46.11.3394-3400.2002
    [36] Perfect JR. Cryptococcus neoformans:A sugar-coated killer with designer genes[J]. Fems Immunol Med Mic, 2005, 45:395-404. doi:  10.1016/j.femsim.2005.06.005
    [37] Ghannoum MA. Potential role of phospholipases in virulence and fungal pathogenesis[J]. Clin Microbiol Rev, 2000, 13:122-143. doi:  10.1128/CMR.13.1.122
    [38] Cox GM, McDade HC, Chen SCA, et al. Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans[J]. Mol Microbiol, 2001, 39:166-175. doi:  10.1046/j.1365-2958.2001.02236.x
    [39] Steenbergen JN, Casadevall A. The origin and maintenance of virulence for the human pathogenic fungus Cryptococcus neoformans[J]. Microbes Infect, 2003, 5:667-675. doi:  10.1016/S1286-4579(03)00092-3
    [40] Ganendren R, Carter E, Sorrell T, et al.Phospholipase B activity enhances adhesion of Cryptococcus neoformans to a human lung epithelial cell line[J]. Microbes Infect, 2006, 8:1006-1015. doi:  10.1016/j.micinf.2005.10.018
    [41] Santangelo R, Zoellner H, Sorrell T, et al. Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model[J]. Infect Immun, 2004, 72:2229-2239. doi:  10.1128/IAI.72.4.2229-2239.2004
    [42] Cox GM, Mukherjee J, Cole GT, et al.Urease as a virulence factor in experimental cryptococcosis[J]. Infect Immun, 2000, 68:443-448. doi:  10.1128/IAI.68.2.443-448.2000
    [43] Kwonchung KJ, Bennett JE. Distribution of alpha and a mating types of Cryptococcus neoformans among natural and clinical isolates[J]. Am J Epidemiol, 1978, 108:337-340. doi:  10.1093/oxfordjournals.aje.a112628
    [44] Kwon-Chung KJ, Edman JC, Wickes BL. Genetic association of mating types and virulence in Cryptococcus neoformans[J]. Infect Immun, 1992, 60:602-605. doi:  10.1128/IAI.60.2.602-605.1992
    [45] Karos M, Chang YC, McClelland CM, et al. Mapping of the Cryptococcus neoformans MAT alpha locus:Presence of mating type-specific mitogen-activated protein kinase cascade homologs[J]. J Bacteriol, 2000, 182:6222-6227. doi:  10.1128/JB.182.21.6222-6227.2000
    [46] Fraser JA, Heitman J. Evolution of fungal sex chromosomes[J]. Mol Microbiol, 2004, 51:299-306. doi:  10.1046/j.1365-2958.2003.03874.x
    [47] Farrer RA, Desjardins CA, Sakthikumar S, et al. Genome evolution and innovation across the four major lineages of Cryptococcus gattii[J]. Mbio, 2015, 6:e00868-15.
    [48] Janbon G, Ormerod KL, Paulet D, et al. Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation[J]. PLoS Genet, 2014, 10:e1004261. doi:  10.1371/journal.pgen.1004261
    [49] Hu G, Wang J, Choi J, et al. Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients[J]. BMC Genomics, 2011, 12:526. doi:  10.1186/1471-2164-12-526
    [50] Hudson RR. Genetic data analysis:Methods for discrete population genetic data[J]. Science, 1990, 250:575. doi:  10.1126/science.250.4980.575
    [51] Saikia S, Oliveira D, Hu G, et al.Role of ferric reductases in iron acquisition and virulence in the fungal pathogen Cryptococcus neoformans[J]. Infect Immun, 2014, 82:839-850. doi:  10.1128/IAI.01357-13
    [52] Aravind L, Koonin EV. The HORMA domain:a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair[J]. Trends Biochem Sci, 1998, 23:284-286.
    [53] van Dijk TB, Gillemans N, Stein C, et al. Friend of Prmt1, a novel chromatin target of protein arginine methyltrans-ferases[J]. Mol cell biol, 2010, 30:260-272.
    [54] Zhang S, Hacham M, Panepinto J, et al. The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activ-ator of laccase in Cryptococcus neoformans[J]. Mol Microbiol, 2006, 62:1090-1101.
    [55] Janbon G, Maeng S, Yang DH, et al. Characterizing the role of RNA silencing components in Cryptococcus neoformans[J]. Fungal Genet Biol, 2010, 47:1070-1080.
    [56] Wang X, Hsueh YP, Li W, et al.Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi[J]. Gene Dev, 2010, 24:2566-2582.
    [57] Gao XD, Tachikawa H, Sato T, et al. Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylation[J]. J Biol Chem, 2005, 280:36254-36262.
    [58] Bochman ML, Sabouri N, Zakian VA. Unwinding the functions of the Pif1 family helicases[J]. DNA Repair, 2010, 9:237-249.
    [59] Giles SS, Perfect JR, Cox GM. Cytochrome c peroxidase contributes to the antioxidant defense of Cryptococcus neoformans[J]. Fungal Genet Biol, 2005, 42:20-29.
    [60] Breitenbach M, Simon B, Probst G, et al. Enolases are highly conserved fungal allergens[J]. Int Arch Allergy Imm, 1997, 113:114-117.
    [61] Kawabe M, Okabe Onokubo A, Arimoto Y, et al. GMC oxidoreductase, a highly expressed protein in a potent biocontrol agent Fusarium oxysporum Cong:1-2, is dispensable for biocontrol activity[J]. J Gen Appl Microbiol, 2011, 57:207-217.
    [62] Sun TS, Ju X, Gao HL, et al. Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis[J]. Nat Commun, 2014, 5:5550.
    [63] Burroughs AM, Allen KN, Dunaway-Mariano D, et al.Evolutionary genomics of the HAD superfamily:understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes[J]. J Mol Biol, 2006, 361:1003-1034.
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