The Impact of Cryptococcus gattii with a Focus on the Outbreak in North America

  • Carla J. Walraven
  • Maximillian Jahng
  • Gregory C. Davenport
  • Hallie Rane
  • Samuel A. Lee
Chapter

Abstract

Cryptococcus gattii is an emerging infectious disease with an expanding geographic range that gained increased attention during the Vancouver Island outbreak in 1999 [54]. Cases of infection with C. gattii were first reported in regions of Africa and Australia [46, 57]. C. gattii has been environmentally isolated from eucalyptus and other trees from tropical and subtropical regions [63, 123]. Prior to the 1999 outbreak, C. gattii infections were extremely rare in temperate regions of North America [12, 87]. Subsequently, C. gattii has been recognized as a cause of outbreak infections in Vancouver Island, British Columbia, and the Pacific Northwest United States. It also has been seen as a cause of low-level sporadic infections in other parts of North America and worldwide. Interestingly, the genotypes of the outbreak C. gattii strains differ from the genotypes of the C. gattii strains causing sporadic infections.

Keywords

Surfactant Dopamine Pneumonia Lignin Superoxide 

Notes

Acknowledgments

This manuscript is dedicated to the memory of our beloved colleague and friend, Dr. Gregory Davenport. We would like to thank Dr. Sarah Hardison for helpful suggestions for the manuscript.

References

  1. 1.
    Alvarado-Ramirez E, Torres-Rodriguez JM, Sellart M, Vidotto V (2008) Laccase activity in Cryptococcus gattii strains isolated from goats. Rev Iberoam Micol 25:150–153PubMedGoogle Scholar
  2. 2.
    Alvarez M, Casadevall A (2006) Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr Biol 16(21):2161–2165PubMedGoogle Scholar
  3. 3.
    Alvarez M, Saylor C, Casadevall A (2008) Antibody action after phagocytosis promotes Cryptococcus neoformans and Cryptococcus gattii macrophage exocytosis with biofilm-like microcolony formation. Cell Microbiol 10:1622–1633PubMedGoogle Scholar
  4. 4.
    Bacon BE, Cherniak R, Kwon-Chung KJ, Jacobson ES (1996) Structure of the 0-deacteylated glucuronoxylomannan from Cryptococcus neoformans Cap70 as determined by 2D NMR spectroscopy. Carbohydr Res 283:95–110PubMedGoogle Scholar
  5. 5.
    Banerjee U, Gupta K, Venugopal P (1997) A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var. neoformans. J Med Vet Mycol 35:139–141PubMedGoogle Scholar
  6. 6.
    Bartlett KH, Kidd SE, Kronstad JW (2007) The emergence of Cryptococcus gattii in British Columbia and the Pacific Northwest. Curr Fungal Infect Rep 10(1):108–115Google Scholar
  7. 7.
    Boekhout T, Theelen B, Diaz M, Fell JW, Hop WCJ, Abeln ECA, Dromer F, Meyer W (2001) Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology 147:891–907PubMedGoogle Scholar
  8. 8.
    Boekhout T, van Belkum A, Leenders AC, Verbrugh HA, Mukamurangwa P, Swinne D, Scheffers WA (1997) Molecular typing of Cryptococcus neoformans: taxonomic and epidemiological aspects. Int J Syst Bacteriol 47(2):432–442PubMedGoogle Scholar
  9. 9.
    Bolanos B, Mitchell TG (1989) Phagocytosis of Cryptococcus neoformans by rat alveolar macrophages. J Med Vet Mycol 27:203–217PubMedGoogle Scholar
  10. 10.
    Bovers M, Hagen F, Kuramae EE, Boekhout T (2008) Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multilocus sequence typing. Fungal Genet Biol 45:400–421PubMedGoogle Scholar
  11. 11.
    Bovers M, Hagen F, Boekhout T (2008) Diversity of the Cryptococcus neoformans-Cryptococcus gattii species complex. Rev Iberoam Micol 25(1):S4–S12PubMedGoogle Scholar
  12. 12.
    Brandt ME, Hutwagner LC, Klug LA, Baughman WS, Rimland D, Cryptococcal Disease Active Surveillance Group et al (1996) Molecular subtype distribution of Cryptococcus neoformans in four areas of the United States. J Clin Microbiol 34(4):912–917PubMedGoogle Scholar
  13. 13.
    Braun DK, Janssen DA, Marcus JR, Kauffman CA (1994) Cryptococcal infection of a prosthetic dialysis fistula. Am J Kidney Dis 24:864–867PubMedGoogle Scholar
  14. 14.
    Brouwer AE, Teparrukkul P, Pinpraphaporn S, Larsen RA, Chierakul W, Peacock S, Day N, White NJ, Harrison TS (2005) Baseline correlation and comparative kinetics of cerebrospinal fluid colony-forming unit counts and antigen titers in cryptococcal meningitis. J Infect Dis 192:681–684PubMedGoogle Scholar
  15. 15.
    Brueske CH (1986) Proteolytic activity of a clinical isolate of Cryptococcus neoformans. J Clin Microbiol 23(3):631–633PubMedGoogle Scholar
  16. 16.
    Byrnes EJ, Marr KA (2011) The outbreak of Cryptococcus gattii in western North America: epidemiology and clinical issues. Curr Infect Dis Rep 13(3):256–261PubMedGoogle Scholar
  17. 17.
    Byrnes EJ, Bartlett KH, Perfect JR, Heitman J (2011) Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals. Microb Infect 13:895–907Google Scholar
  18. 18.
    Byrnes EJ, Li W, Ren P, Lewit Y, Voelz K, Fraser JA, Dietrich FS, May RC, Chaturvedi S, Chaturvedi V, Heitman J (2011) A diverse population of Cryptococcus gattii molecular type VGIII in southern Californian HIV/AIDS patients. PLoS Pathog 7(9):e1002205PubMedGoogle Scholar
  19. 19.
    Byrnes EJ, Li W, Lewit Y, Ma H, Voelz K, Ren P, Carter DA, Chaturvedi V, Bildfell RJ, May RC, Heitman J (2010) Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 6(4):e1000850PubMedGoogle Scholar
  20. 20.
    Byrnes EJ, Bildfell RJ, Frank SA, Mitchell TG, Marr KA, Heitman J (2009) Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States. J Infect Dis 199:1081–1086PubMedGoogle Scholar
  21. 21.
    Campbell LT, Currie BJ, Krockenberger M, Malik R, Meyer W, Heitman J, Carter D (2005) Clonality and recombination in genetically differentiated subgroups of Cryptococcus gattii. Eukaryot Cell 4(8):1403–1409PubMedGoogle Scholar
  22. 22.
    Campbell LT, Fraser JA, Nichols CB, Dietrich FS, Carter D, Heitman J (2005) Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity. Eukaryot Cell 4:1410–1419PubMedGoogle Scholar
  23. 23.
    Carriconde F, Gilgado F, Arthur I, Ellis D, Malik R, van de Wiele N, Robert V, Currie BJ, Meyer W (2011) Clonality and α-a recombination in the Australian Cryptococcus gattii VGII population–an emerging outbreak in Australia. PLoS One 6(2):e16936PubMedGoogle Scholar
  24. 24.
    Casadevall A, Perfect JR (1998) Cryptococcus neoformans. ASM Press, Washington, DC, USAGoogle Scholar
  25. 25.
    Centers for Disease Control and Prevention (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. MMWR 58(RR-4):1–207Google Scholar
  26. 26.
    Charlier C, Chretien F, Baudrimont M, Mordelet E, Lortholary O, Dromer F (2005) Capsule structure changes associated with Cryptococcus neoformans crossing of the blood–brain barrier. Am J Pathol 166:421–432PubMedGoogle Scholar
  27. 27.
    Chaturvedi S, Dyavaiah M, Larsen RA, Chaturvedi V (2005) Cryptococcus gattii in AIDS patients, southern California. Emerg Infect Dis 11:1686–1692PubMedGoogle Scholar
  28. 28.
    Chayakulkeeree M, Perfect JR (2006) Cryptococcosis. Infect Dis Clin North Am 20(3):507–544, v–viPubMedGoogle Scholar
  29. 29.
    Chen LC, Blank ES, Casadevall A (1996) Extracellular proteinase activity of Cryptococcus neoformans. Clin Diagn Lab Immunol 3(5):570–574PubMedGoogle Scholar
  30. 30.
    Chen S, Sorrell T, Nimmo G, Speed B, Currie B, Ellis D, Marriott D, Pfeiffer T, Parr D, Byth K, Australasian Cryptococcal Study Group (2000) Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Clin Infect Dis 31(2):499–508PubMedGoogle Scholar
  31. 31.
    Chen SCA, Wright LC, Golding JC, Sorrell TC (2000) Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans. Biochem J 347(2):431–439PubMedGoogle Scholar
  32. 32.
    Chen SCA, Currie BJ, Campbell HM, Fisher DA, Pfeiffer TJ, Ellis DH, Sorrell TC (1997) Cryptococcus neoformans var. gattii infection in northern Australia: existence of an environmental source other than known host eucalypts. Trans R Soc Trop Med Hyg 91:547–550PubMedGoogle Scholar
  33. 33.
    Cheng PY, Sham A, Kronstad JW (2009) Cryptococcus gattii isolates from the British Columbia cryptococcosis outbreak induce less protective inflammation in a murine model of infection than Cryptococcus neoformans. Infect Immun 77:4284–4294PubMedGoogle Scholar
  34. 34.
    Cherniak R, Sundstrom JB (1994) Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect Immun 62(5):1507–1512PubMedGoogle Scholar
  35. 35.
    Chong HS, Dagg R, Malik R, Chen S, Carter D (2010) In vitro susceptibility of the yeast pathogen Cryptococcus to fluconazole and other azoles varies with molecular genotype. J Clin Microbiol 48(11):4115–4120PubMedGoogle Scholar
  36. 36.
    Chowdhary A, Randhawa HS, Sundar G, Kathuria S, Prakash A, Khan Z, Sun S, Xu J (2011) In vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii serotype B from north-western India. J Med Microbiol 60(7):961–967PubMedGoogle Scholar
  37. 37.
    Clemons KV, Calich VL, Burger E, Filler SG, Grazziutti M, Murphy J, Roilides E, Campa A, Dias MR, Edwards JE Jr, Fu Y, Fernandes-Bordignon G, Ibrahim A, Katsifa H, Lamaignere CG, Meloni-Bruneri LH, Rex J, Savary CA, Xidieh C (2000) Pathogenesis I: interactions of host cells and fungi. Med Mycol 38(Suppl 1):99–111PubMedGoogle Scholar
  38. 38.
    D’Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M, Hu G, Jung WH, Sham A, Kidd SE, Tangen K, Lee N, Zeilmaker T, Sawkins J, McVicker G, Shah S, Gnerre S, Griggs A, Zeng Q, Bartlett K, Li W, Wang X, Heitman J, Stajich JE, Fraser JA, Meyer W, Carter D, Schein J, Krzywinski M, Kwon-Chung KJ, Varma A, Wang J, Brunham R, Fyfe M, Ouellette BF, Siddiqui A, Marra M, Jones S, Holt R, Birren BW, Galagan JE, Cuomo CA (2011) Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. mBio 2(1):e00342–10PubMedGoogle Scholar
  39. 39.
    Datta K, Bartlett KH, Baer R, Byrnes E, Galanis E, Heitman J, Hoang L, Leslie MJ, MacDougall L, Magill SS, Morshed MG, Marr KA et al (2009) Spread of Cryptococcus gattii into Pacific Northwest region of the United States. Emerg Infect Dis 15(8):1185–1191PubMedGoogle Scholar
  40. 40.
    Datta K, Bartlett KH, Marr KA (2009) Cryptococcus gattii: emergence in western north America: exploitation of a novel ecological niche. Interdiscip Perspect Infect Dis 2009:176532PubMedGoogle Scholar
  41. 41.
    DeBess E, Cieslak PR, Marsden-Haug N, Goldoft M, Wohrle R, Free C, Dykstra E, Nett RJ, Chiller T, Lockhart SR, Harris J (2010) Emergence of Cryptococcus gattii—Pacific Northwest, 2004–2010. MMWR Morb Mortal Wkly Rep 59(28):865–868Google Scholar
  42. 42.
    Diaz MR, Boekhout T, Kiesling T, Fell JW (2005) Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast Cryptococcus neoformans. FEMS Yes Res 5:129–1140Google Scholar
  43. 43.
    Diaz MR, Boekhout T, Theelen B, Fell JW (2000) Molecular sequence analyses of the intergenic spacer (IGS) associated with rDNA of the two varieties of the pathogenic yeast, Cryptococcus neoformans. Syst Appl Microbiol 23(4):535–545PubMedGoogle Scholar
  44. 44.
    Dong ZM, Murphy JW (1995) Effects of the two varieties of Cryptococcus neoformans cells and culture filtrate antigens on neutrophil locomotion. Infect Immun 63:2632–2644PubMedGoogle Scholar
  45. 45.
    Ellis DH (1987) Cryptococcus neoformans var. gattii in Australia. J Clin Microbiol 25(2):430–431PubMedGoogle Scholar
  46. 46.
    Ellis DH, Pfeiffer TJ (1990) Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol 28(7):1642–1644PubMedGoogle Scholar
  47. 47.
    Erickson T, Liu L, Gueyikian A, Zhu X, Gibbons J, Williamson PR (2001) Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1. Mol Microbiol 42:1121–1131PubMedGoogle Scholar
  48. 48.
    Erke KH (1976) Light microscopy of basidia, basidiospores, and nuclei in spores and hyphae of Filobasidiella neoformans (Cryptococcus neoformans). J Bacteriol 128:445–455PubMedGoogle Scholar
  49. 49.
    Feldmesser M, Tucker S, Casadevall A (2001) Intracellular parasitism of macrophages by Cryptococcus neoformans. Trends Microbiol 9(6):273–278PubMedGoogle Scholar
  50. 50.
    Findley K, Rodriguez-Carres M, Metin B, Kroiss J, Fonseca A, Vilgalys R, Heitman J (2009) Phylogeny and phenotypic characterization of pathogenic cryptococcus species and closely related saprobic taxa in the tremellales. Eukaryt Cell 8:353–361Google Scholar
  51. 51.
    Fonseca FL, Nohara LL, Cordero RJ, Frases S, Casadevall A, Almeida IC, Nimrichter L, Rodrigues ML (2010) Immunomodulatory effects of serotype B glucuronoxylomannan from Cryptococcus gattii correlate with polysaccharide diameter. Infect Immun 78(9):3861–3870PubMedGoogle Scholar
  52. 52.
    Fraser JA, Giles SS, Wenink EC, Geunes-Boyer SG, Wright JR, Diezmann S, Allen A, Stajich JE, Dietrich FS, Perfect JR, Heitman J (2005) Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature 437:1360–1364PubMedGoogle Scholar
  53. 53.
    Fraser JA, Subaran RL, Nichols CB, Heitman J (2003) Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: implications for an outbreak on Vancouver Island, Canada. Eukaryot Cell 2:1036–1045PubMedGoogle Scholar
  54. 54.
    Fyfe M, MacDougall L, Romney M, Starr M, Pearce M, Mak S, Mithani S, Kibsey P (2008) Cryptococcus gattii infections on Vancouver Island, British Columbia, Canada: emergence of a tropical fungus in a temperate environment. Can Commun Dis Rep 34(6):1–12PubMedGoogle Scholar
  55. 55.
    Galanis E, MacDougall L, Kidd S, Morshed M, British Columbia Cryptococcus gattii Working Group (2010) Epidemiology of Cryptococcocus gattii, British Columbia, Canada, 1999–2007. Emerg Infect Dis 16(2):251–257PubMedGoogle Scholar
  56. 56.
    Garcia-Hermoso D, Dromer F, Janbon G (2004) Cryptococcus neoformans capsule structure evolution in vitro and during murine infection. Infect Immun 72:3359–3365PubMedGoogle Scholar
  57. 57.
    Gatti F, Eeckels R (1970) An atypical strain of Cryptococcus neoformans (San Felice) Vuillemin 1894. I. Description of the disease and of the strain. Ann Soc Belges Med Trop Parasitol Mycol 50:689–693PubMedGoogle Scholar
  58. 58.
    Giles SS, Batinic-Haberle I, Perfect JR, Cox GM (2005) Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth. Eukaryot Cell 4:46–54PubMedGoogle Scholar
  59. 59.
    Gillece JD, Schupp JM, Balajee SA, Harris J, Pearson T, Yan Y, Keim P, DeBess E, Marsden-Haug N, Wohrle R, Engelthaler DM, Lockhart SR (2011) Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity. PLoS One 6:e28550PubMedGoogle Scholar
  60. 60.
    Goulart L, Silva LK, Chiapello L, Silveira C, Crestani J, Masih D, Vainstein MH (2010) Cryptococcus neoformans and Cryptococcus gattii genes preferentially expressed during rat macrophage infection. Med Mycol 48:932–941PubMedGoogle Scholar
  61. 61.
    Granger DL, Perfect JR, Durack DT (1985) Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J Clin Invest 76:508–516PubMedGoogle Scholar
  62. 62.
    Gupta G, Fries BC (2010) Variability of phenotypic traits in Cryptococcus varieties and species and the resulting implications for pathogenesis. Future Microbiol 5(5):775–787PubMedGoogle Scholar
  63. 63.
    Hagen F, Boekhout T (2010) The search for the natural habitat of Cryptococcus gattii. Mycopathologia 170:209–211PubMedGoogle Scholar
  64. 64.
    Hagen F, van Assen S, Luijckx GJ, Boekhout T, Kampinga GA (2010) Activated dormant Cryptococcus gattii infection in a Dutch tourist who visited Vancouver Island (Canada): a molecular epidemiological approach. Med Mycol 48(3):528–531PubMedGoogle Scholar
  65. 65.
    Hagen F, Illnait-Zaragozi MT, Bartlett KH, Swinne D, Geertsen E, Klaassen CH, Boekhout T, Meis JF (2010) In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental Cryptococcus gattii isolates. Antimicrob Agents Chemother 54(12):5139–5145PubMedGoogle Scholar
  66. 66.
    Harris J, Lockhart S, Chiller T (2012) Cryptococcus gattii: where do we go from here? Med Mycol 50:113–129PubMedGoogle Scholar
  67. 67.
    Harris JR, Lockhart SR, Debess E, Marsden-Haug N, Goldoft M, Wohrle R, Lee S, Smelser C, Park B, Chiller T (2011) Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis 53(12):1188–1195PubMedGoogle Scholar
  68. 68.
    Hoang LM, Maguire JA, Doyle P, Fyfe M, Roscoe DL (2004) Cryptococcus neoformans infections at Vancouver Hospital and Health Sciences Centre (1997–2002): epidemiology, microbiology and histopathology. J Med Microbiol 53(9):935–940PubMedGoogle Scholar
  69. 69.
    Hu G, Steen BR, Lian T, Sham AP, Tam N, Tangen KL, Kronstad JW (2007) Transcriptional regulation by protein kinase A in Cryptococcus neoformans. PLoS Pathog 3(3):e42PubMedGoogle Scholar
  70. 70.
    Iqbal N, DeBess EE, Wohrle R, Sun B, Nett RJ, Ahlquist AM, Chiller T, Lockhart SR, Cryptococcus gattii Public Health Working Group (2010) Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii strains from the Pacific Northwest of the United States. J Clin Microbiol 48(2):539–544PubMedGoogle Scholar
  71. 71.
    Iqbal N, Illnait-Zaragozi MT, Bartlett KH, Swinne D, Geertsen E, Klaassen CH, Boekhout T, Meis JF (2010) In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental Cryptococcus gattii isolates. Antimicrob Agents Chemother 54(12):5139–5145Google Scholar
  72. 72.
    Ikeda R, Shinoda T, Morita T, Jacobson ES (1993) Characterization of a phenol oxidase from Cryptococcus neoformans var. neoformans. Microbiol Immunol 37:759–764PubMedGoogle Scholar
  73. 73.
    Ito-Kuwa S, Nakamura K, Aoki S, Vidotto V (2007) Serotype identification of Cryptococcus neoformans by multiplex PCR. Mycoses 50(4):277–281PubMedGoogle Scholar
  74. 74.
    Jackson A, Hosseinipour MC (2010) Management of cryptococcal meningitis in sub-saharan Africa. Curr HIV/AIDS Rep 7(3):134–142PubMedGoogle Scholar
  75. 75.
    Jacobson ES, Emery HS (1991) Temperature regulation of the cryptococcal phenoloxidase. J Med Vet Mycol 29:121–124PubMedGoogle Scholar
  76. 76.
    Jain N, Li L, Hsueh YP, Guerrero A, Heitman J, Goldman DL, Fries BC (2009) Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans. Infect Immun 7(7):128–140Google Scholar
  77. 77.
    Jain N, Li L, McFadden DC, Banarjee U, Wang X, Cook E, Fries BC (2006) Phenotypic switching in a Cryptococcus neoformans variety gattii strain is associated with changes in virulence and promotes dissemination to the central nervous system. Infect Immun 74(2):896–903PubMedGoogle Scholar
  78. 78.
    Kerkering TM, Duma RJ, Shadomy S (1981) The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors. Ann Intern Med 94(5):611–616PubMedGoogle Scholar
  79. 79.
    Khan ZU, Randhawa HS, Chehadeh W, Chowdhary A, Kowshik T, Chandy R (2009) Cryptococcus neoformans serotype A and Cryptococcus gattii serotype B isolates differ in their susceptibilities to fluconazole and voriconazole. Int J Antimicrob Agents 33(6):559–563PubMedGoogle Scholar
  80. 80.
    Kidd SE, Hagen F, Tscharke RL, Huynh M, Bartlett KH, Fyfe M, MacDougall L, Boekhout T, Kwon-Chung KJ, Meyer W (2004) A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci 101:17258–17263PubMedGoogle Scholar
  81. 81.
    Kidd SE, Sorrell TC, Meyer W (2003) Isolation of two molecular types of Cryptococcus neoformans var. gattii from insect frass. Med Mycol 41(2):171–176PubMedGoogle Scholar
  82. 82.
    Kwon-Chung KJ (1980) Nuclear genotypes of spore chains in Filobasidiella neoformans (Cryptococcus neoformans). Mycologia 72:418–422PubMedGoogle Scholar
  83. 83.
    Kwon-Chung KJ (1976) Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68:821–833PubMedGoogle Scholar
  84. 84.
    Kwon-Chung KJ, Bennett JE (1984) Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol 120(1):123–130PubMedGoogle Scholar
  85. 85.
    Kwong-Chung KJ, Bennett JE (1978) Distribution of α and α mating types of Cryptococcus neoformans among natural and clinical isolates. Am J Epidemiol 108(4):337–340Google Scholar
  86. 86.
    Kwon-Chung KJ, Boekhout T, Fell JW, Diaz M (2002) Proposal to conserve the name Cryptococcus gattii against C. hondurianus and C. bacillisporus (Basidiomycota, Hymenomycetes, Tremellomycetidae). Taxon 51:804–806Google Scholar
  87. 87.
    Kwon-Chung KJ, Polacheck I, Bennett JE (1982) Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (serotypes A and D) and Cryptococcus neoformans var. gattii (serotypes B and C). J Clin Microbiol 15:525–537Google Scholar
  88. 88.
    Larsen RA, Bozzette SA, Jones BE, Haghighat D, Leal MA, Forthal D, Bauer M, Tilles JG, McCutchan JA, Leedom JM (1994) Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis 19(4):741–745PubMedGoogle Scholar
  89. 89.
    Laurenson IF, Lalloo DG, Naragi S, Seaton RA, Trevett AJ, Matuka A, Kevau IH (1997) Cryptococcus neoformans in Papua New Guinea: a common pathogen but an elusive source. J Med Vet Mycol 35(6):437–440PubMedGoogle Scholar
  90. 90.
    Lee A, Toffaletti DL, Tenor J, Soderblom EJ, Thompson JW, Moseley MA, Price M, Perfect JR (2010) Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis. Infect Immun 78:4213–4225PubMedGoogle Scholar
  91. 91.
    Lin X, Hull CM, Heitman J (2005) Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434(7036):1017–1021PubMedGoogle Scholar
  92. 92.
    Litvintseva AP, Thakur R, Reller LB, Mitchell TG (2005) Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in sub-Saharan Africa. J Infect Dis 192(5):888–892PubMedGoogle Scholar
  93. 93.
    Littman ML, Tsubura E (1959) Effect of degree of encapsulation upon virulence of Cryptococcus neoformans. Proc Soc Exp Biol Med 101:773–777PubMedGoogle Scholar
  94. 94.
    Liu L, Tewari RP, Williamson PR (1999) Laccase protects Cryptococcus neoformans from antifungal activity of alveolar macrophages. Infect Immun 67:6034–6039PubMedGoogle Scholar
  95. 95.
    Lupo P, Chang YC, Kelsall BL, Farber JM, Pietrella D, Vecchiarelli A, Leon F, Kwon-Chung KJ (2008) The presence of capsule in Cryptococcus neoformans influences the gene expression profile in dendritic cells during interaction with the fungus. Infect Immun 76(4):1581–1589PubMedGoogle Scholar
  96. 96.
    Ma H, Hagen F, Stekel DJ, Johnston SA, Sionov E, Falk R, Polacheck I, Boekhout T, May RC (2009) The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation. Proc Natl Acad Sci USA 106(31):12980–12985PubMedGoogle Scholar
  97. 97.
    MacDougall L, Fyfe M (2006) Emergence of Cryptococcus gattii in a novel environment provides clues to its incubation period. J Clin Microbiol 44(5):1581–1582Google Scholar
  98. 98.
    MacDougall L, Fyfe M, Romney M, Starr M, Galanis E (2011) Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis 17(2):193–199PubMedGoogle Scholar
  99. 99.
    MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR, Kronstad JW, Morshed MG, Bartlett KH (2007) Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis 13(1):42–50PubMedGoogle Scholar
  100. 100.
    Mackenzie EA, Klig LS (2008) Computational modeling and in silico analysis of differential regulation of myo-inositol catabolic enzymes in Cryptococcus neoformans. BMC Mol Biol 9:88. doi: 10.1186/1471-2199-9-88 PubMedGoogle Scholar
  101. 101.
    Mak S, Klinkenberg B, Bartlett K, Fyfe M (2010) Ecological niche modeling of Cryptococcus gattii in British Columbia, Canada. Environ Health Perspect 118(5):653–658PubMedGoogle Scholar
  102. 102.
    Martinez LR, Casadevall A (2006) Cryptococcus neoformans cells in biofilms are less susceptible than planktonic cells to antimicrobial molecules produced by the innate immune system. Infect Immun 74:6118–6123PubMedGoogle Scholar
  103. 103.
    Martinez LR, Casadevall A (2006) Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother 50:1021–1033PubMedGoogle Scholar
  104. 104.
    Martinez LR, Christaki E, Casadevall A (2006) Specific antibody to Cryptococcus neoformans glucurunoxylomannan antagonizes antifungal drug action against cryptococcal biofilms in vitro. J Infect Dis 194:261–266PubMedGoogle Scholar
  105. 105.
    Meyer W, Trilles L (2010) Genotyping of the Cryptococcus neoformans/C. gattii species complex. Aust Biochemist 41:11–15Google Scholar
  106. 106.
    Meyer W, Gilfado F, Ngamskulrungroj P, Trilles L, Hagen F, Castaneda E, Boekhout T (2011) Molecular typing of the Cryptococcus neoformans/Cryptococcus gattii species complex. In: Heitman J, Kozel TJ, Kwon-Chung KJ, Perfect JR, Casadevall A (eds) Cryptococcus: from human pathogen to model yeast. ASM Press, Washington, DC, USAGoogle Scholar
  107. 107.
    Monari C, Bistoni F, Vecchiarelli A (2006) Glucuronoxylomannan exhibits potent immunosuppressive properties. FEMS Yeast Res 6(4):537–542PubMedGoogle Scholar
  108. 108.
    Montagna MT, Viviani MA, Pulito A, Aralla C, Tortorano AM, Fiore L, Barbuti S (1997) Cryptococcus neoformans var. gattii in Italy. Note II. Environmental investigation related to an autochthonous clinical case in Apulia. J Mycol Med 7:93–96Google Scholar
  109. 109.
    Muller HE, Sethi KK (1972) Proteolytic activity of Cryptococcus neoformans against human plasma proteins. Med Microbiol Immunol 158(2):129–134PubMedGoogle Scholar
  110. 110.
    Muller U, Stenzel W, Kohler G, Werner C, Polte T, Hansen G, Schutze N, Straubinger RK, Blessing M, McKenzie AN, Brombacher F, Alber G (2007) IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans. J Immunol 179:5367–5377PubMedGoogle Scholar
  111. 111.
    Narasipura SD, Chaturvedi V, Chaturvedi S (2005) Characterization of Cryptococcus neoformans variety gattii SOD2 reveals distinct roles of the two superoxide dismutases in fungal biology and virulence. Mol Microbiol 55(6):1782–1800PubMedGoogle Scholar
  112. 112.
    Neilson JB, Fromtling RA, Blumer GS (1981) Pseudohyphal forms of Cryptococcus neoformans: decreased survival in vivo. Mycopathologia 73:57–59PubMedGoogle Scholar
  113. 113.
    Neilson JB, Ivey MH, Bulmer GS (1978) Cryptococcus neoformans pseudohyphal forms surviving culture with Acanthamoeba polyphaga. Infect Immun 20:262–266PubMedGoogle Scholar
  114. 114.
    Ngamskulrungroj P, Serena C, Gilgado F, Malik R, Meyer W (2011) Global VGIIa isolates are of comparable virulence to the major fatal Cryptococcus gattii Vancouver Island outbreak genotype. Clin Microbiol Infect 17(2):251–258PubMedGoogle Scholar
  115. 115.
    Ngamskulrungroj P, Gilgado F, Faganello J, Litvintseva AP, Leal AL, Tsui KM, Mitchell TG, Vainstein MH, Meyer W (2009) Genetic diversity of the Cryptococcus species complex suggests that Cryptococcus gattii deserves to have varieties. PLoS One 4:e5862PubMedGoogle Scholar
  116. 116.
    Ngamskulrungroj P, Himmelreich U, Breger JA, Wilson C, Chayakulkeeree M, Krockenberger MB, Malik R, Daniel HM, Toffaletti D, Djordjevic JT, Mylonakis E, Meyer W, Perfect JR (2009) The trehalose synthesis pathway is an integral part of the virulence composite for Cryptococcus gattii. Infect Immun 77:4584–4596PubMedGoogle Scholar
  117. 117.
    Ngamskulrungroj P, Serena C, Gilgado F, Malik R, Meyer W (2011) Global VGIIa isolates are of comparable virulence to the major fatal Cryptococcus gattii Vancouver Island outbreak genotype. Clin Microbiol Infect 17(2):251–258PubMedGoogle Scholar
  118. 118.
    Nosanchuk JD, Casadevall A (1997) Cellular charge of Cryptococcus neoformans: contributions from the capsular polysaccharide, melanin, and monoclonal antibody binding. Infect Immun 65:1836–1841PubMedGoogle Scholar
  119. 119.
    Nussbaum JC, Jackson A, Namarika D, Phulusa J, Kenala J, Kanyemba C, Jarvis JN, Jaffar S, Hosseinipour MC, Kamwendo D, van der Horst CM, Harrison TS (2010) Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis 50(3):338–344PubMedGoogle Scholar
  120. 120.
    Olszewski MA, Noverr MC, Chen GH, Toews GB, Cox GM, Perfect JR, Huffnagle GB (2004) Urease expression by Cryptococcus neoformans promotes microvascular sequestration, thereby enhancing central nervous system invasion. Am J Pathol 164(5):1761–1771PubMedGoogle Scholar
  121. 121.
    Pappas PG, Chetchotisakd P, Larsen RA, Manosuthi W, Morris MI, Anekthananon T, Sungkanuparph S, Supparatpinyo K, Nolen TL, Zimmer LO, Kendrick AS, Johnson P, Sobel JD, Filler SG (2009) A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis 48(12):1775–1783PubMedGoogle Scholar
  122. 122.
    Pfeiffer T, Ellis D (1991) Environmental isolation of Cryptococcus neoformans gattii from California. J Infect Dis 163:929–930PubMedGoogle Scholar
  123. 123.
    Penk A, Pittrow L (1999) Role of fluconazole in the long-term suppressive therapy of fungal infections in patients with artificial implants. Mycoses 42:91–96PubMedGoogle Scholar
  124. 124.
    Perfect JR (2006) Cryptococcus neoformans: a sugar-coated killer. In: Heitman J, Filler S, Edwards J, Mitchell A (eds) Molecular principles of fungal pathogenesis. ASM Press, Washington, DCGoogle Scholar
  125. 125.
    Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC (2010) Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 50(3):291–322PubMedGoogle Scholar
  126. 126.
    Pettit RK, Repp KK, Hazen KC (2010) Temperature affects the susceptibility of Cryptococcus neoformans biofilms to antifungal agents. Med Mycol 48(2):421–426PubMedGoogle Scholar
  127. 127.
    Petzold EW, Himmelreich U, Mylonakis E, Rude T, Toffaletti D, Cox GM, Miller JL, Perfect JR (2006) Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans. Infect Immun 74:5877–5887PubMedGoogle Scholar
  128. 128.
    Pfeiffer TJ, Ellis DH (1992) Environmental isolation of Cryptococcus neoformans var. gattii from Eucalyptus tereticornis. J Med Vet Mycol 30:407–408PubMedGoogle Scholar
  129. 129.
    Pfieffer TJ, Ellis DH (1991) Environmental isolation of Cryptococcus neoformans var. gattii from California. J Infect Dis 163:929–930Google Scholar
  130. 130.
    Ren P, Springer DJ, Behr MJ, Samsonoff WA, Chaturvedi S, Chaturvedi V (2006) Transcription factor STE12α has distinct roles in morphogenesis, virulence, and ecological fitness of the primary pathogenic yeast Cryptococcus gattii. Eukaryot Cell 5:1065–1080PubMedGoogle Scholar
  131. 131.
    Rivera J, Feldmesser M, Cammer M, Casadevall A (1998) Organ-dependent variation of capsule thickness in Cryptococcus neoformans during experimental murine infection. Infect Immun 66:5027–5030PubMedGoogle Scholar
  132. 132.
    Ruma-Haynes P, Brownlee AG, Sorrell TC (2000) A rapid method for detecting extracellular proteinase activity in Cryptococcus neoformans and a survey of 63 isolates. J Med Microbiol 49(8):733–737PubMedGoogle Scholar
  133. 133.
    Rutherford JC, Lin X, Nielsen K, Heitman J (2008) Amt2 permease is required to induce ammonium-responsive invasive growth and mating in Cryptococcus neoformans. Eukaryot Cell 7:237–246PubMedGoogle Scholar
  134. 134.
    Shen WC, Davidson RC, Cox GM, Heitman J (2002) Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot Cell 1:366–377PubMedGoogle Scholar
  135. 135.
    Silva DC, Martins MA, Szeszs MW, Bonfietti LX, Matos D, Melhem MS (2012) Susceptibility to antifungal agents and genotypes of Brazilian clinical and environmental Cryptococcus gattii strains. Diagn Microbiol Infect Dis 72(4):332–339PubMedGoogle Scholar
  136. 136.
    Sorell TC (2001) Cryptococcus neoformans variety gattii. Med Mycol 39:155–168Google Scholar
  137. 137.
    Speed B, Dunt D (1995) Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 21(1):28–34PubMedGoogle Scholar
  138. 138.
    Springer DJ, Chaturvedi V (2010) Projecting global occurrence of Cryptococcus gattii. Emerg Infect Dis 16(1):14–20PubMedGoogle Scholar
  139. 139.
    Springer DJ, Ren P, Raina R, Dong Y, Behr MJ, McEwen BF, Bowser SS, Samsonoff WA, Chaturvedi S, Chaturvedi V (2010) Extracellular fibrils of pathogenic yeast Cryptococcus gattii are important in ecological niche colonization and mammalian virulence. PLoS One 5:e10978PubMedGoogle Scholar
  140. 140.
    Steele KT, Thakur R, Nthobatsang R, Steenhoff AP, Bisson GP (2010) In-hospital mortality of HIV-infected cryptococcal meningitis patients with C. gattii and C. neoformans infection in Gaborone, Botswana. Med Mycol 48(8):1112–1115PubMedGoogle Scholar
  141. 141.
    Steen BR, Zuyderduyn S, Toffaletti DL, Marra M, Jones SJ, Perfect JR, Kronstad J (2003) Cryptococcus neoformans gene expression during experimental cryptococcal meningitis. Eukaryot Cell 2:1336–1349PubMedGoogle Scholar
  142. 142.
    Stephen C, Lester S, Black W, Fyfe M, Raverty S (2002) Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia. Can Vet J 43(10):792–794PubMedGoogle Scholar
  143. 143.
    Tay ST, Tanty Haryanty T, Ng KP, Rohani MY, Hamimah H (2006) In vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii to five antifungal drugs. Mycoses 49(4):324–330PubMedGoogle Scholar
  144. 144.
    Thompson GR, Wiederhold NP, Fothergill AW, Vallor AC, Wickes BL, Patterson TF (2009) Antifungal susceptibilities among different serotypes of Cryptococcus gattii and Cryptococcus neoformans. Antimicrob Agents Chemother 53(1):309–311PubMedGoogle Scholar
  145. 145.
    Torres-Rodríguez JM, Alvarado-Ramírez E, Gutiérrez-Gallego R (2008) Urease activity in Cryptococcus neoformans and Cryptococcus gattii. Rev Iberoam Micol 25(1):27–31PubMedGoogle Scholar
  146. 146.
    Trilles L, Meyer W, Wanke B, Guarro J, Lazéra M (2012) Correlation of antifungal susceptibility and molecular type within the Cryptococcus neoformans/C. gattii species complex. Med Mycol 50(3):328–332PubMedGoogle Scholar
  147. 147.
    Trilles L, Fernández-Torres B, Lazéra Mdos S, Wanke B, Guarro J (2004) In vitro antifungal susceptibility of Cryptococcus gattii. J Clin Microbiol 42(10):4815–4817PubMedGoogle Scholar
  148. 148.
    Upton A, Fraser JA, Kidd SE, Bretz C, Bartlett KH, Heitman J, Marr KA (2007) First contemporary case of human infection with Cryptococcus gattii in Puget Sound: evidence for spread of the Vancouver Island outbreak. J Clin Microbiol 45(9):3086–3088PubMedGoogle Scholar
  149. 149.
    Voelz K, Lammas DA, May RC (2009) Cytokine signaling regulates the outcome of intracellular macrophage parasitism by Cryptococcus neoformans. Infect Immun 77(8):3450–3457PubMedGoogle Scholar
  150. 150.
    Walsh TJ, Schlegel R, Moody MM, Costerton JW, Salcman M (1986) Ventriculoatrial shunt infection due to Cryptococcus neoformans: an ultrastructural and quantitative microbiological study. Neurosurgery 18:373–375PubMedGoogle Scholar
  151. 151.
    Walraven CJ, Gerstein W, Hardison SE, Wormley F, Lockhart SR, Harris JR, Fothergill A, Wickes B, Gober-Wilcox J, Massie L, Ku TS, Firacative C, Meyer W, Lee SA (2011) Fatal disseminated Cryptococcus gattii infection in New Mexico. PLoS One 6(12):e28625PubMedGoogle Scholar
  152. 152.
    Williamson PR (1994) Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase. J Bacteriol 176:656–664PubMedGoogle Scholar
  153. 153.
    Varma A, Kwon-Chung KJ (2010) Heteroresistance of Cryptococcus gattii to fluconazole. Antimicrob Agents Chemother 54(6):2303–2311PubMedGoogle Scholar
  154. 154.
    Vartivarian SE, Anaissie EJ, Cowart RE, Sprigg HA, Tingler MJ, Jacobson ES (1993) Regulation of cryptococcal capsular polysaccharide by iron. J Infect Dis 167:186–190PubMedGoogle Scholar
  155. 155.
    Velagapudi R, Hsueh YP, Geunes-Boyer S, Wright JR, Heitman J (2009) Spores as infectious propagules of Cryptococcus neoformans. Infect Immun 77:4345–4355PubMedGoogle Scholar
  156. 156.
    Vecchiarelli A, Pericolini E, Gabrielli E, Chow SK, Bistoni F, Cenci E, Casadevall A (2011) Cryptococcus neoformans galactoxylomannan is a potent negative immunomodulator, inspiring new approaches in anti-inflammatory immunotherapy. Immunotherapy 3(8):997–1005PubMedGoogle Scholar
  157. 157.
    Voelz K, Lammas DA, May RC (2009) Cytokine signaling regulates the outcome of intracellular macrophage parasitism by Cryptococcus neoformans. Infect Immun 77(8):3450–3457PubMedGoogle Scholar
  158. 158.
    World Health Organization (WHO) (2011) Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. http://whqlibdoc.who.int/publications/2011/9789241502979_eng.pdf. Accessed 11/01/2013
  159. 159.
    Xu J, Vilgalys R, Mitchell TG (2000) Multiple gene genealogies reveal recent dispersion and hybridization in the human pathogenic fungus Cryptococcus neoformans. Mol Ecol 9:1471–1481PubMedGoogle Scholar
  160. 160.
    Young BJ, Kozel TR (1993) Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect Immunol 61(7):2966–2972Google Scholar
  161. 161.
    Yue C, Cavallo LM, Alspaugh JA, Wang P, Cox GM, Perfect JR, Heitman J (1999) The STE12α homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. Genetics 153:1601–1615PubMedGoogle Scholar
  162. 162.
    Zaragoza O, Casadevall A (2004) Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online 6:10–15PubMedGoogle Scholar
  163. 163.
    Zaragoza O, Rodrigues ML, De Jesus M, Frases S, Dadachova E, Casadevall A (2009) The capsule of the fungal pathogen Cryptococcus neoformans. Adv Appl Microbiol 6(8):133–216Google Scholar
  164. 164.
    Zaragoza O, Telzak A, Bryan RA, Dadachova E, Casadevall A (2006) The polysaccharide capsule of the pathogenic fungus Cryptococcus neoformans enlarges by distal growth and is rearranged during budding. Mol Microbiol 59:67–83PubMedGoogle Scholar
  165. 165.
    Zaragoza O, Fries BC, Casadevall A (2003) Induction of capsule growth in Cryptococcus neoformans by mammalian serum and CO(2). Infect Immun 71:6155–6164PubMedGoogle Scholar
  166. 166.
    Zaragoza O, Taborda CP, Casadevall A (2003) The efficacy of complement-mediated phagocytosis of Cryptococcus neoformans is dependent on the location of C3 in the polysaccharide capsule and involves both direct and indirect C3-mediated interactions. Eur J Immunol 33:1957–1967PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carla J. Walraven
    • 1
  • Maximillian Jahng
    • 2
  • Gregory C. Davenport
    • 1
  • Hallie Rane
    • 2
  • Samuel A. Lee
    • 2
    • 1
  1. 1.University of New Mexico Health Science CenterAlbuquerqueUSA
  2. 2.Division of Infectious DiseasesNew Mexico Veterans Healthcare SystemAlbuquerqueUSA

Personalised recommendations