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Annual Review of Microbiology

Volume 73, 2019

Life Cycle of

Abstract

is a ubiquitous environmental fungus and an opportunistic pathogen that causes fatal cryptococcal meningitis. Advances in genomics, genetics, and cellular and molecular biology of have dramatically improved our understanding of this important pathogen, rendering it a model organism to study eukaryotic biology and microbial pathogenesis. In light of recent progress, we describe in this review the life cycle of with a special emphasis on the regulation of the yeast-to-hypha transition and different modes of sexual reproduction, in addition to the impacts of the life cycle on cryptococcal populations and pathogenesis.

Keyword(s): dimorphism, life cycle, mating, morphogenesis, pathogenesis, sexual reproduction

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2019-09-08
2024-04-24
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Literature Cited

  1. 1. 
    Alanio A, Vernel-Pauillac F, Sturny-Leclere A, Dromer F 2015. Cryptococcus neoformans host adaptation: toward biological evidence of dormancy. mBio 6:e02580–14
     [Google Scholar]
  2. 2. 
    Albuquerque P, Casadevall A. 2012. Quorum sensing in fungi—a review. Med. Mycol. 50:337–45
     [Google Scholar]
  3. 3. 
    Aliouat El M, Dujardin L, Martinez A, Duriez T, Ricard I, Dei-Cas E 1999. Pneumocystis carinii growth kinetics in culture systems and in hosts: involvement of each life cycle parasite stage. J. Eukaryot. Microbiol. 46:116S–17S
     [Google Scholar]
  4. 4. 
    Almeida JM, Cisse OH, Fonseca A, Pagni M, Hauser PM 2015. Comparative genomics suggests primary homothallism of Pneumocystis species. mBio 6:e02250–14
     [Google Scholar]
  5. 5. 
    Alspaugh JA, Cavallo LM, Perfect JR, Heitman J 2000. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol. Microbiol 36:352–65
     [Google Scholar]
  6. 6. 
    Alvarez M, Casadevall A. 2006. Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr. Biol. 16:2161–65
     [Google Scholar]
  7. 7. 
    Bahn YS, Kojima K, Cox GM, Heitman J 2005. Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol. Biol. Cell 16:2285–300
     [Google Scholar]
  8. 8. 
    Bassler BL, Miller MB. 2013. Quorum sensing. The Prokaryotes: Prokaryotic Communities and Ecophysiology E Rosenberg, EF DeLong, S Lory, E Stackebrandt, F Thompson 495–509 Berlin: Springer
     [Google Scholar]
  9. 9. 
    Botts MR, Giles SS, Gates MA, Kozel TR, Hull CM 2009. Isolation and characterization of Cryptococcus neoformans spores reveal a critical role for capsule biosynthesis genes in spore biogenesis. Eukaryot. Cell 8:595–605
     [Google Scholar]
  10. 10. 
    Botts MR, Hull CM. 2010. Dueling in the lung: how Cryptococcus spores race the host for survival. Curr. Opin. Microbiol. 13:437–42
     [Google Scholar]
  11. 11. 
    Boyce KJ, Andrianopoulos A. 2015. Fungal dimorphism: the switch from hyphae to yeast is a specialized morphogenetic adaptation allowing colonization of a host. FEMS Microbiol. Rev. 39:797–811
     [Google Scholar]
  12. 12. 
    Brandao F, Esher SK, Ost KS, Pianalto K, Nichols CB et al. 2018. HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence. Sci. Rep. 8:5209
     [Google Scholar]
  13. 13. 
    Brefort T, Doehlemann G, Mendoza-Mendoza A, Reissmann S, Djamei A, Kahmann R 2009. Ustilago maydis as a pathogen. Annu. Rev. Phytopathol. 47:423–45
     [Google Scholar]
  14. 14. 
    Caballero Van Dyke MC, Wormley FL Jr 2018. A call to arms: quest for a cryptococcal vaccine. Trends Microbiol 26:436–46
     [Google Scholar]
  15. 15. 
    Casadevall A. 2012. Amoeba provide insight into the origin of virulence in pathogenic fungi. Adv. Exp. Med. Biol. 710:1–10
     [Google Scholar]
  16. 16. 
    Casadevall A, Pirofski LA. 2018. A therapeutic vaccine for recurrent vulvovaginal candidiasis. Clin. Infect. Dis. 66:1937–39
     [Google Scholar]
  17. 17. 
    Catania S, Dumesic PA, Stoddard C, Cooke S, Burke J et al. 2017. Epigenetic maintenance of DNA methylation after evolutionary loss of the de novo methyltransferase. bioRxiv 149385
  18. 18. 
    Chacko N, Zhao Y, Yang E, Wang L, Cai JJ, Lin X 2015. The lncRNA RZE1 controls cryptococcal morphological transition. PLOS Genet 11:e1005692
     [Google Scholar]
  19. 19. 
    Chang ALD, Tamara L. 2018. Maintenance of mitochondrial morphology in Cryptococcus neoformans is critical for stress resistance and virulence. mBio 9:e01375–18
     [Google Scholar]
  20. 20. 
    Chang YC, Miller GF, Kwon-Chung KJ 2003. Importance of a developmentally regulated pheromone receptor of Cryptococcus neoformans for virulence. Infect. Immun. 71:4953–60
     [Google Scholar]
  21. 21. 
    Chang YC, Penoyer LA, Kwon-Chung KJ 2001. The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. PNAS 98:3258–63
     [Google Scholar]
  22. 22. 
    Chang YC, Wickes BL, Miller GF, Penoyer LA, Kwon-Chung KJ 2000. Cryptococcus neoformans STE12α regulates virulence but is not essential for mating. J. Exp. Med. 191:871–82
     [Google Scholar]
  23. 23. 
    Chang YC, Wright LC, Tscharke RL, Sorrell TC, Wilson CF, Kwon-Chung KJ 2004. Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12αp. Mol. Microbiol. 53:1385–96
     [Google Scholar]
  24. 24. 
    Charlier C, Nielsen K, Daou S, Brigitte M, Chretien F, Dromer F 2009. Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans. Infect. Immun 77:120–27
     [Google Scholar]
  25. 25. 
    Chen Y, Litvintseva AP, Frazzitta AE, Haverkamp MR, Wang LY et al. 2015. Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana. Mol. Ecol. 24:3559–71
     [Google Scholar]
  26. 26. 
    Choi J, Jung WH, Kronstad JW 2015. The cAMP/protein kinase A signaling pathway in pathogenic basidiomycete fungi: connections with iron homeostasis. J. Microbiol. 53:579–87
     [Google Scholar]
  27. 27. 
    Chow EWL, Clancey SA, Billmyre RB, Averette AF, Granek JA et al. 2017. Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans. PLOS Genet 13:e1006667
     [Google Scholar]
  28. 28. 
    Coelho C, Bocca AL, Casadevall A 2014. The intracellular life of Cryptococcus neoformans. Annu. Rev. Pathol 9:219–38
     [Google Scholar]
  29. 29. 
    Cogliati M. 2013. Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii: an atlas of the molecular types. Scientifica 2013:675213
     [Google Scholar]
  30. 30. 
    Crabtree JN, Okagaki LH, Wiesner DL, Strain AK, Nielsen JN, Nielsen K 2012. Titan cell production enhances the virulence of Cryptococcus neoformans. Infect. Immun 80:3776–85
     [Google Scholar]
  31. 31. 
    Cramer KL, Gerrald QD, Nichols CB, Price MS, Alspaugh JA 2006. Transcription factor Nrg1 mediates capsule formation, stress response, and pathogenesis in Cryptococcus neoformans. Eukaryot. Cell 5:1147–56
     [Google Scholar]
  32. 32. 
    Cruz MC, Fox DS, Heitman J 2001. Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans. EMBO J 20:1020–32
     [Google Scholar]
  33. 33. 
    Cushion MT, Smulian AG, Slaven BE, Sesterhenn T, Arnold J et al. 2007. Transcriptome of Pneumocystis carinii during fulminate infection: carbohydrate metabolism and the concept of a compatible parasite. PLOS ONE 2:e423
     [Google Scholar]
  34. 34. 
    Davidson RC, Nicholls CB, Cox GM, Perfect JR, Heitman J 2003. A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans. Mol. Microbiol 49:469–85
     [Google Scholar]
  35. 35. 
    Desjardins CA, Giamberardino C, Sykes SM, Yu CH, Tenor JL et al. 2017. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res 27:1207–19
     [Google Scholar]
  36. 36. 
    Dover J, Schneider J, Tawiah-Boateng MA, Wood A, Dean K et al. 2002. Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6. J. Biol. Chem. 277:28368–71
     [Google Scholar]
  37. 37. 
    Dromer F, Casadevall A, Perfect J, Sorrell T 2011. Cryptococcus neoformans: latency and disease. From Human Pathogen to Model Yeast J Heitman, T Kozel, K Kwon-Chung, J Perfect, A Casadevall 431–39 Washington, DC: ASM
     [Google Scholar]
  38. 38. 
    D'Souza CA, Alspaugh JA, Yue CL, Harashima T, Cox GM et al. 2001. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol 21:3179–91
     [Google Scholar]
  39. 39. 
    Edwards JE Jr, Schwartz MM, Schmidt CS, Sobel JD, Nyirjesy P et al. 2018. A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis—a phase 2 randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 66:1928–36
     [Google Scholar]
  40. 40. 
    Erenpreisa J, Salmina K, Huna A, Jackson TR, Vazquez-Martin A, Cragg MS 2015. The “virgin birth”, polyploidy, and the origin of cancer. Oncoscience 2:3–14
     [Google Scholar]
  41. 41. 
    Evans EE. 1950. The antigenic composition of Cryptococcus neoformans. I. A serologic classification by means of the capsular and agglutination reactions. J. Immunol. 64:423–30
     [Google Scholar]
  42. 42. 
    Feretzaki M, Billmyre RB, Clancey SA, Wang XY, Heitman J 2016. Gene network polymorphism illuminates loss and retention of novel RNAi silencing components in the Cryptococcus pathogenic species complex. PLOS Genet 12:e1005868
     [Google Scholar]
  43. 43. 
    Feretzaki M, Heitman J. 2013. Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans. PLOS Genet 9:e1003688
     [Google Scholar]
  44. 44. 
    Findley K, Sun S, Fraser JA, Hsueh YP, Averette AF et al. 2012. Discovery of a modified tetrapolar sexual cycle in Cryptococcus amylolentus and the evolution of MAT in the Cryptococcus species complex. PLOS Genet 8:e1002528
     [Google Scholar]
  45. 45. 
    Finkel-Jimenez B, Wüthrich M, Klein BS 2002. BAD1, an essential virulence factor of Blastomyces dermatitidis, suppresses host TNF-α production through TGF-β-dependent and -independent mechanisms. J. Immunol. 168:5746–55
     [Google Scholar]
  46. 46. 
    Forsythe A, Vogan A, Xu JP 2016. Genetic and environmental influences on the germination of basidiospores in the Cryptococcus neoformans species complex. Sci. Rep. 6:33828
     [Google Scholar]
  47. 47. 
    Franzot SP, Salkin IF, Casadevall A 1999. Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. J. Clin. Microbiol 37:838–40
     [Google Scholar]
  48. 48. 
    Fraser J, Hsueh Y, Findley K, Heitman J 2006. Evolution of the mating-type locus: the basidiomycetes. Sex in Fungi: Molecular Determination and Evolutionary Implications J Heitman, J Kronstad, J Taylor, L Casselton 19–34 Washington, DC: ASM
     [Google Scholar]
  49. 49. 
    Fraser JA, Diezmann S, Subaran RL, Allen A, Lengeler KB et al. 2004. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms. PLOS Biol 2:2243–55
     [Google Scholar]
  50. 50. 
    Fraser JA, Giles SS, Wenink EC, Geunes-Boyer SG, Wright JR et al. 2005. Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature 437:1360–64
     [Google Scholar]
  51. 51. 
    Fraser JA, Heitman J. 2003. Fungal mating-type loci. Curr. Biol. 13:R792–95
     [Google Scholar]
  52. 52. 
    Fromtling RA, Blackstock R, Hall NK, Bulmer GS 1979. Immunization of mice with an avirulent pseudohyphal form of Cryptococcus neoformans. Mycopathologia 68:179–81
     [Google Scholar]
  53. 53. 
    Fu C, Donadio N, Cardenas ME, Heitman J 2018. Dissecting the roles of the calcineurin pathway in unisexual reproduction, stress responses, and virulence in Cryptococcus deneoformans. Genetics 208:639–53
     [Google Scholar]
  54. 54. 
    Fu C, Heitman J. 2017. PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex. PLOS Genet 13:e1007113
     [Google Scholar]
  55. 55. 
    Fu J, Mares C, Lizcano A, Liu Y, Wickes BL 2011. Insertional mutagenesis combined with an inducible filamentation phenotype reveals a conserved STE50 homologue in Cryptococcus neoformans that is required for monokaryotic fruiting and sexual reproduction. Mol. Microbiol. 79:990–1007
     [Google Scholar]
  56. 56. 
    Gauthier GM. 2015. Dimorphism in fungal pathogens of mammals, plants, and insects. PLOS Pathog 11:e1004608
     [Google Scholar]
  57. 57. 
    Gerstein AC, Fu MS, Mukaremera L, Li ZM, Ormerod KL et al. 2015. Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation. mBio 6:e01340–15
     [Google Scholar]
  58. 58. 
    Giles SS, Dagenais TR, Botts MR, Keller NP, Hull CM 2009. Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans. Infect. Immun 77:3491–500
     [Google Scholar]
  59. 59. 
    Gyawali R, Lin X. 2013. Prezygotic and postzygotic control of uniparental mitochondrial DNA inheritance in Cryptococcus neoformans. mBio 4:e00112-13
     [Google Scholar]
  60. 60. 
    Gyawali R, Upadhyay S, Way J, Lin X 2017. A family of secretory proteins is associated with different morphotypes in Cryptococcus neoformans. Appl. Environ. Microb 83:e02967–16
     [Google Scholar]
  61. 61. 
    Gyawali R, Zhao Y, Lin J, Fan Y, Xu X et al. 2017. Pheromone independent unisexual development in Cryptococcus neoformans. PLOS Genet 13:e1006772
     [Google Scholar]
  62. 62. 
    Hagen F, Ceresini PC, Polacheck I, Ma H, van Nieuwerburgh F et al. 2013. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest. PLOS ONE 8:e71148
     [Google Scholar]
  63. 63. 
    Hagen F, Khayhan K, Theelen B, Kolecka A, Polacheck I et al. 2015. Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. Fungal Genet. Biol. 78:16–48
     [Google Scholar]
  64. 64. 
    Hartmann HA, Kruger J, Lottspeich F, Kahmann R 1999. Environmental signals controlling sexual development of the corn smut fungus Ustilago maydis through the transcriptional regulator Prf1. Plant Cell 11:1293–305
     [Google Scholar]
  65. 65. 
    Haynes BC, Skowyra ML, Spencer SJ, Gish SR, Williams M et al. 2011. Toward an integrated model of capsule regulation in Cryptococcus neoformans. PLOS Pathog 7:e1002411
     [Google Scholar]
  66. 66. 
    Heimel K, Scherer M, Vranes M, Wahl R, Pothiratana C et al. 2010. The transcription factor Rbf1 is the master regulator for b-mating type controlled pathogenic development in Ustilago maydis. PLOS Pathog 6:e1001035
     [Google Scholar]
  67. 67. 
    Heitman J. 2012. Sexual reproduction and virulence of Cryptococcus. Mycoses 55:22
     [Google Scholar]
  68. 68. 
    Heitman J. 2015. Evolution of sexual reproduction: a view from the fungal kingdom supports an evolutionary epoch with sex before sexes. Fungal Biol. Rev. 29:108–17
     [Google Scholar]
  69. 69. 
    Heitman J, Kronstad JW, Taylor JW, Casselton LA 2007. Preface. Sex in Fungi Molecular Determination and Evolutionary Implications J Heitman, Kronstad JW, Taylor JW, Casselton LA, pp. xv–xvii Washington, DC: ASM
     [Google Scholar]
  70. 70. 
    Heller S, McLean RA, Campbell CG, Jones IH 1957. A case of coexistent nonmeningitic cryptococcosis and Boeck's sarcoid. Am. J. Med. 22:986–94
     [Google Scholar]
  71. 71. 
    Hicks JK, D'Souza CA, Cox GM, Heitman J 2004. Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans. Eukaryot. Cell 3:14–26
     [Google Scholar]
  72. 72. 
    Hicks JK, Heitman J. 2007. Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade. Eukaryot. Cell 6:413–20
     [Google Scholar]
  73. 73. 
    Hipsher K, Lin J, Lin X 2019. Identification of host-protective antigens on the surface ofCryptococcus neoformans Presented at 30th Fungal Genetics Conference Pacific Grove, CA: http://conferences.genetics-gsa.org/fungal/2019/index
  74. 74. 
    Homer CM, Summers DK, Goranov AI, Clarke SC, Wiesner DL et al. 2016. Intracellular action of a secreted peptide required for fungal virulence. Cell Host Microbe 19:849–64
     [Google Scholar]
  75. 75. 
    Hornby JM, Jensen EC, Lisec AD, Tasto JJ, Jahnke B et al. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microb. 67:2982–92
     [Google Scholar]
  76. 76. 
    Hsueh YP, Shen WC. 2005. A homolog of Ste6, the a-factor transporter in Saccharomyces cerevisiae, is required for mating but not for monokaryotic fruiting in Cryptococcus neoformans. Eukaryot. Cell 4:147–55
     [Google Scholar]
  77. 77. 
    Hsueh YP, Xue CY, Heitman J 2007. G protein signaling governing cell fate decisions involves opposing G alpha subunits in Cryptococcus neoformans. Mol. Biol. Cell 18:3237–49
     [Google Scholar]
  78. 78. 
    Huang MW, Hebert AS, Coon JJ, Hull CM 2015. Protein composition of infectious spores reveals novel sexual development and germination factors in Cryptococcus. PLOS Genet 11:e1005490
     [Google Scholar]
  79. 79. 
    Hull CM, Boily MJ, Heitman J 2005. Sex-specific homeodomain proteins Sxi1α and Sxi2a coordinately regulate sexual development in Cryptococcus neoformans. Eukaryot. Cell 4:526–35
     [Google Scholar]
  80. 80. 
    Hull CM, Davidson RC, Heitman J 2002. Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1α. Gene Dev 16:3046–60
     [Google Scholar]
  81. 81. 
    Hull CM, Heitman J. 2002. Genetics of Cryptococcus neoformans. Annu. Rev. Genet 36:557–615
     [Google Scholar]
  82. 82. 
    Idnurm A, Heitman J. 2005. Light controls growth and development via a conserved pathway in the fungal kingdom. PLOS Biol 3:615–26
     [Google Scholar]
  83. 83. 
    Janbon G, Maeng S, Yang DH, Ko YJ, Jung KW et al. 2010. Characterizing the role of RNA silencing components in Cryptococcus neoformans. Fungal Genet. Biol 47:1070–80
     [Google Scholar]
  84. 84. 
    Jones SK, Bennett RJ. 2011. Fungal mating pheromones: choreographing the dating game. Fungal Genet. Biol. 48:668–76
     [Google Scholar]
  85. 85. 
    Jung KW, Kim SY, Okagaki LH, Nielsen K, Bahn YS 2011. Ste50 adaptor protein governs sexual differentiation of Cryptococcus neoformans via the pheromone-response MAPK signaling pathway. Fungal Genet. Biol. 48:154–65
     [Google Scholar]
  86. 86. 
    Jung KW, Lee KT, Averette AF, Hoy MJ, Everitt J et al. 2018. Evolutionarily conserved and divergent roles of unfolded protein response (UPR) in the pathogenic Cryptococcus species complex. Sci. Rep. 8:8132
     [Google Scholar]
  87. 87. 
    Kaffarnik F, Muller P, Leibundgut M, Kahmann R, Feldbrugge M 2003. PKA and MAPK phosphorylation of Prf1 allows promoter discrimination in Ustilago maydis. EMBO J 22:5817–26
     [Google Scholar]
  88. 88. 
    Kajiwara S, Yamaoka K, Hori K, Miyazawa H, Saito T et al. 1992. Isolation and sequence of a developmentally regulated putative novel gene, priA, from the basidiomycete Lentinus edodes. Gene 114:173–78
     [Google Scholar]
  89. 89. 
    Kaur JN, Panepinto JC. 2016. Morphotype-specific effector functions of Cryptococcus neoformans PUM1. Sci. Rep 6:23638
     [Google Scholar]
  90. 90. 
    Kozubowski L, Heitman J. 2012. Profiling a killer, the development of Cryptococcus neoformans. FEMS Microbiol. Rev 36:78–94
     [Google Scholar]
  91. 91. 
    Kruzel EK, Giles SS, Hull CM 2012. Analysis of Cryptococcus neoformans sexual development reveals rewiring of the pheromone-response network by a change in transcription factor identity. Genetics 191:435–49
     [Google Scholar]
  92. 92. 
    Kutty G, Achaz G, Maldarelli F, Varma A, Shroff R et al. 2010. Characterization of the meiosis-specific recombinase Dmc1 of Pneumocystis. J. Infect. Dis 202:1920–29
     [Google Scholar]
  93. 93. 
    Kwon-Chung KJ. 1975. A new genus, Filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia 67:1197–200
     [Google Scholar]
  94. 94. 
    Kwon-Chung KJ. 1980. Nuclear genotypes of spore chains in Filobasidiella neoformans (Cryptococcus neoformans). Mycologia 72:418–22
     [Google Scholar]
  95. 95. 
    Kwon-Chung KJ, Bennett JE. 1978. Distribution of a and alpha mating types of Cryptococcus neoformans among natural and clinical isolates. Am. J. Epidemiol. 108:337–40
     [Google Scholar]
  96. 96. 
    Kwon-Chung KJ, Bennett JE, Wickes BL, Meyer W, Cuomo CA et al. 2017. The case for adopting the “species complex” nomenclature for the etiologic agents of cryptococcosis. mSphere 2:e00357–16
     [Google Scholar]
  97. 97. 
    Kwon-Chung KJ, Bennett JE, Rhodes JC 1982. Taxonomic studies on Filobasidiella species and their anamorphs. Antonie Van Leeuwenhoek 48:25–38
     [Google Scholar]
  98. 98. 
    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 51:804–6
     [Google Scholar]
  99. 99. 
    Kwon-Chung KJ, Edman JC, Wickes BL 1992. Genetic association of mating types and virulence in Cryptococcus neoformans. Infect. Immun 60:602–5
     [Google Scholar]
  100. 100. 
    Kwon-Chung KJ, Hill WB. 1981. Sexuality and pathogenicity of Filobasidiella neoformans (Cryptococcus neoformans). Sexuality and Pathogenicity of Fungi R Vanbreuseghem, C DeVroey 243–50 Paris: Masson
     [Google Scholar]
  101. 101. 
    Kwon-Chung KJ, Popkin TJ. 1976. Ultrastructure of septal complex in Filobasidiella neoformans (Cryptococcus neoformans). J. Bacteriol. 126:524–28
     [Google Scholar]
  102. 102. 
    Lanver D, Tollot M, Schweizer G, Lo Presti L, Reissmann S et al. 2017. Ustilago maydis effectors and their impact on virulence. Nat. Rev. Microbiol. 15:409–21
     [Google Scholar]
  103. 103. 
    Lee H, Chang YC, Nardone G, Kwon-Chung KJ 2007. TUP1 disruption in Cryptococcus neoformans uncovers a peptide-mediated density-dependent growth phenomenon that mimics quorum sensing. Mol. Microbiol. 64:591–601
     [Google Scholar]
  104. 104. 
    Lengeler KB, Cox GM, Heitman J 2001. Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Infect. Immun. 69:115–22
     [Google Scholar]
  105. 105. 
    Lengeler KB, Fox DS, Fraser JA, Allen A, Forrester K et al. 2002. Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryot. Cell 1:704–18
     [Google Scholar]
  106. 106. 
    Lev S, Desmarini D, Chayakulkeeree M, Sorrell TC, Djordjevic JT 2012. The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity. PLOS ONE 7:e51403
     [Google Scholar]
  107. 107. 
    Levitz SM. 1991. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev. Infect. Dis. 13:1163–69
     [Google Scholar]
  108. 108. 
    Li L, Shen G, Zhang ZG, Wang YL, Thompson JK, Wang P 2007. Canonical heterotrimeric G proteins regulating mating and virulence of Cryptococcus neoformans. Mol. Biol. Cell 18:4201–9
     [Google Scholar]
  109. 109. 
    Lin J, Idnurm A, Lin X 2015. Morphology and its underlying genetic regulation impact the interaction between Cryptococcus neoformans and its hosts. Med. Mycol. 53:493–504
     [Google Scholar]
  110. 110. 
    Lin J, Zhao Y, Yang E, Ferraro A, Lewis Z, Lin X 2019. Transcription factor Znf2 coordinates with SWI/SNF chromatin remodeling complex in sexual development ofCryptococcus neoformans Presented at 30th Fungal Genetics Conference Pacific Grove, CA: http://conferences.genetics-gsa.org/fungal/2019/index
  111. 111. 
    Lin X, Alspaugh JA, Liu H, Harris S 2015. Fungal morphogenesis. CSH Perspect. Med. 5:a019679
     [Google Scholar]
  112. 112. 
    Lin X, Huang J, Mitchell TG, Heitman J 2006. Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATα allele enhances filamentation. PLOS Genet 2:1801–14
     [Google Scholar]
  113. 113. 
    Lin X, Hull CM, Heitman J 2005. Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434:1017–21
     [Google Scholar]
  114. 114. 
    Lin X, Jackson JC, Feretzaki M, Xue C, Heitman J 2010. Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans. PLOS Genet 6:e1000953
     [Google Scholar]
  115. 115. 
    Lin X, Litvintseva AP, Nielsen K, Patel S, Floyd A et al. 2007. αADα hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness. PLOS Genet 3:1975–90
     [Google Scholar]
  116. 116. 
    Lin X, Patel S, Litvintseva AP, Floyd A, Mitchell TG, Heitman J 2009. Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating. PLOS Pathog 5:e1000283
     [Google Scholar]
  117. 117. 
    Litvintseva AP, Mitchell TG. 2012. Population genetic analyses reveal the African origin and strain variation of Cryptococcus neoformans var. grubii. PLOS Pathog. 8:e1002495
     [Google Scholar]
  118. 118. 
    Liu KH, Shen WC. 2011. Mating differentiation in Cryptococcus neoformans is negatively regulated by the Crk1 protein kinase. Fungal Genet. Biol. 48:225–40
     [Google Scholar]
  119. 119. 
    Liu LX, He GJ, Chen L, Zheng J, Chen YY et al. 2018. Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans. eLife 7:e38683
     [Google Scholar]
  120. 120. 
    Liu YP, Filler SG. 2011. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot. Cell 10:168–73
     [Google Scholar]
  121. 121. 
    Ma HS, Croudace JE, Lammas DA, May RC 2006. Expulsion of live pathogenic yeast by macrophages. Curr. Biol. 16:2156–60
     [Google Scholar]
  122. 122. 
    Madhani HD, Fink GR. 1998. The control of filamentous differentiation and virulence in fungi. Trends Cell Biol 8:348–53
     [Google Scholar]
  123. 123. 
    Magditch DA, Liu T, Xue C, Idnurm A 2012. DNA mutations mediate microevolution between host-adapted forms of the pathogenic fungus Cryptococcus neoformans. PLOS Pathog 8:e1002936
     [Google Scholar]
  124. 124. 
    McBride JA, Gauthier GM, Klein BS 2018. Turning on virulence: mechanisms that underpin the morphologic transition and pathogenicity of Blastomyces. Virulence In press
     [Google Scholar]
  125. 125. 
    Mead ME, Stanton BC, Kruzel EK, Hull CM 2015. Targets of the sex inducer homeodomain proteins are required for fungal development and virulence in Cryptococcus neoformans. Mol. Microbiol 95:804–18
     [Google Scholar]
  126. 126. 
    Meng Y, Fan Y, Liao W, Lin X 2018. Plant homeodomain genes play important roles in cryptococcal yeast-hypha transition. Appl. Environ. Microb. 84:e01732–17
     [Google Scholar]
  127. 127. 
    Metin B, Findley K, Heitman J 2010. The mating type locus (MAT) and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi. PLOS Genet 6:e1000961
     [Google Scholar]
  128. 128. 
    Meyer W, Castaneda A, Jackson S, Huynh M, Castaneda E, Study IC 2003. Molecular typing of IberoAmerican Cryptococcus neoformans isolates. Emerg. Infect. Dis. 9:189–95
     [Google Scholar]
  129. 129. 
    Neilson JB, Ivey MH, Bulmer GS 1978. Cryptococcus neoformans—pseudohyphal forms surviving culture with Acanthamoeba polyphaga. Infect. Immun 20:262–6
     [Google Scholar]
  130. 130. 
    Ni M, Feretzaki M, Sun S, Wang XY, Heitman J 2011. Sex in fungi. Annu. Rev. Genet. 45:405–30
     [Google Scholar]
  131. 131. 
    Nielsen K, Cox GM, Litvintseva AP, Mylonakis E, Malliaris SD et al. 2005. Cryptococcus neoformans α strains preferentially disseminate to the central nervous system during coinfection. Infect. Immun. 73:4922–33
     [Google Scholar]
  132. 132. 
    Nielsen K, Cox GM, Wang P, Toffaletti DL, Perfect JR, Heitman J 2003. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect. Immun. 71:4831–41
     [Google Scholar]
  133. 133. 
    Okagaki LH, Nielsen K. 2012. Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections. Eukaryot. Cell 11:820–26
     [Google Scholar]
  134. 134. 
    Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ et al. 2010. Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLOS Pathog 6:e1000953
     [Google Scholar]
  135. 135. 
    O'Meara TR, Hay C, Price MS, Giles S, Alspaugh JA 2010. Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host. Eukaryot. Cell 9:1193–202
     [Google Scholar]
  136. 136. 
    Otto B. 1894. Ueber parasitäre Zelleinschlüsse und ihre Züchtung. Centralblatt Bakteriol. Parasitenkd. 16:175–80
     [Google Scholar]
  137. 137. 
    Padder SA, Prasad R, Shah AH 2018. Quorum sensing: a less known mode of communication among fungi. Microbiol. Res. 210:51–58
     [Google Scholar]
  138. 138. 
    Park HS, Chow EWL, Fu C, Soderblom EJ, Moseley MA et al. 2016. Calcineurin targets involved in stress survival and fungal virulence. PLOS Pathog 12:e1005873
     [Google Scholar]
  139. 139. 
    Perfect JR. 2015. Cryptococcosis (Cryptococcus neoformans and Cryptococcus gattii). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseasesκ, ed. JE Bennett, R Dolin, MJ Blaser 2934–48 Philadelphia: Elsevier. , 8th ed..
     [Google Scholar]
  140. 140. 
    Perfect JR, Casadevall A. 2002. Cryptococcosis. Infect. Dis. Clin. N. Am. 16:837–74
     [Google Scholar]
  141. 141. 
    Peters SE, English K, Rana A, Akter S, Malik S et al. 2001. Synaptonemal complexes in the pre-cyst of Pneumocystis carinii. J. Eukaryot. Microbiol 48:Suppl.134S
     [Google Scholar]
  142. 142. 
    Pukkila-Worley R, Alspaugh JA. 2004. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Res 4:361–67
     [Google Scholar]
  143. 143. 
    Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP et al. 2017. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect. Dis. 17:873–81
     [Google Scholar]
  144. 144. 
    Rhodes J, Desjardins CA, Sykes SM, Beale MA, Vanhove M et al. 2017. Tracing genetic exchange and biogeography of Cryptococcus neoformans var. grubii at the global population level. Genetics 207:327–46
     [Google Scholar]
  145. 145. 
    Roach KC, Heitman J. 2014. Unisexual reproduction reverses Muller's ratchet. Genetics 198:1059–69
     [Google Scholar]
  146. 146. 
    Roberts RL, Fink GR. 1994. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. Gene Dev 8:2974–85
     [Google Scholar]
  147. 147. 
    Roth C, Sun S, Billmyre RB, Heitman J, Magwene PM 2018. A high-resolution map of meiotic recombination in Cryptococcus deneoformans demonstrates decreased recombination in unisexual reproduction. Genetics 209:567–78
     [Google Scholar]
  148. 148. 
    Sanfelice F. 1895. Sull'azione patogena dei blastomiceti. Anal. d'Igiene Sper. 5:239–62
     [Google Scholar]
  149. 149. 
    Shadomy HJ. 1970. Clamp connections in two strains of Cryptococcus neoformans. Recent Trends in Yeast Research DG Ahearn 67–72 Atlanta: Sch. Arts Sci., Ga. State Univ.
     [Google Scholar]
  150. 150. 
    Shadomy HJ, Utz JP. 1966. Preliminary studies on a hyphaforming mutant of Cryptococcus neoformans. Mycologia 58:383–90
     [Google Scholar]
  151. 151. 
    Shen WC, Davidson RC, Cox GM, Heitman J 2002. Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot. Cell 1:366–77
     [Google Scholar]
  152. 152. 
    Sorrell T, Chen S, Phillips P, Marr K 2011. Clinical perspectives on Cryptococcus neoformans and Cryptococcus gattii: implications for diagnosis and management. Cryptococcus J Heitman, T Kozel, JK Kwon-Chung, J Perfect, A Casadevall 595–606 Washington, DC: ASM
     [Google Scholar]
  153. 153. 
    Steenbergen JN, Shuman HA, Casadevall A 2001. Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages. PNAS 98:15245–50
     [Google Scholar]
  154. 154. 
    Sukroongreung S, Kitiniyom K, Nilakul C, Tantimavanich S 1998. Pathogenicity of basidiospores of Filobasidiella neoformans var. neoformans. Med. Mycol. 36:419–24
     [Google Scholar]
  155. 155. 
    Sun S, Billmyre RB, Mieczkowski PA, Heitman J 2014. Unisexual reproduction drives meiotic recombination and phenotypic and karyotypic plasticity in Cryptococcus neoformans. PLOS Genet 10:e1004849
     [Google Scholar]
  156. 156. 
    Sun S, Heitman J. 2015. From two to one: unipolar sexual reproduction. Fungal Biol. Rev. 29:118–25
     [Google Scholar]
  157. 157. 
    Sun S, Yadav V, Billmyre RB, Cuomo CA, Nowrousian M et al. 2017. Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination. PLOS Biol 15:e2002527
     [Google Scholar]
  158. 158. 
    Thewes S. 2014. Calcineurin-Crz1 signaling in lower eukaryotes. Eukaryot. Cell 13:694–705
     [Google Scholar]
  159. 159. 
    Tian X, He G, Hu P, Chen L, Tao C et al. 2018. Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide. Nat. Microbiol. 3:698–707
     [Google Scholar]
  160. 160. 
    Toffaletti DL, Nielsen K, Dietrich F, Heitman J, Perfect JR 2004. Cryptococcus neoformans mitochondrial genomes from serotype A and D strains do not influence virulence. Curr. Genet. 46:193–204
     [Google Scholar]
  161. 161. 
    Tucker SC, Casadevall A. 2002. Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm. PNAS 99:3165–70
     [Google Scholar]
  162. 162. 
    Velagapudi R, Hsueh YP, Geunes-Boyer S, Wright JR, Heitman J 2009. Spores as infectious propagules of Cryptococcus neoformans. Infect. Immun 77:4345–55
     [Google Scholar]
  163. 163. 
    Voelz K, Johnston SA, Smith LM, Hall RA, Idnurm A, May RC 2014. ‘Division of labour’ in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak. Nat. Commun. 5:5194
     [Google Scholar]
  164. 164. 
    Vuillemin J-P. 1901. Les blastomycètes pathogènes. Rev. Gén. Sci. Pures Appl. 12:732–51
     [Google Scholar]
  165. 165. 
    Walton FJ, Idnurm A, Heitman J 2005. Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans. Mol. Microbiol 57:1381–96
     [Google Scholar]
  166. 166. 
    Wang L, Lin X. 2015. The morphotype heterogeneity in Cryptococcus neoformans. Curr. Opin. Microbiol 26:60–64
     [Google Scholar]
  167. 167. 
    Wang L, Tian X, Gyawali R, Lin X 2013. Fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner. PNAS 110:11571–76
     [Google Scholar]
  168. 168. 
    Wang L, Tian X, Gyawali R, Upadhyay S, Foyle D et al. 2014. Morphotype transition and sexual reproduction are genetically associated in a ubiquitous environmental pathogen. PLOS Pathog 10:e1004185
     [Google Scholar]
  169. 169. 
    Wang L, Zhai B, Lin X 2012. The link between morphotype transition and virulence in Cryptococcus neoformans. PLOS Pathog 8:e1002765
     [Google Scholar]
  170. 170. 
    Wang P, Nichols CB, Lengeler MB, Cardenas ME, Cox GM et al. 2002. Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans. Eukaryot. Cell 1:257–72
     [Google Scholar]
  171. 171. 
    Wang P, Perfect JR, Heitman J 2000. The G-protein β subunit GPB1 is required for mating and haploid fruiting in Cryptococcus neoformans. Mol. Cell. Biol 20:352–62
     [Google Scholar]
  172. 172. 
    Wang XY, Hsueh YP, Li WJ, Floyd A, Skalsky R, Heitman J 2010. Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Gene Dev 24:2566–82
     [Google Scholar]
  173. 173. 
    Wickes BL, Edman U, Edman JC 1997. The Cryptococcus neoformans STE12α gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific. Mol. Microbiol. 26:951–60
     [Google Scholar]
  174. 174. 
    Wickes BL, Mayorga ME, Edman U, Edman JC 1996. Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type. PNAS 93:7327–31
     [Google Scholar]
  175. 175. 
    Wilson DE, Bennett JE, Bailey JW 1968. Serologic grouping of Cryptococcus neoformans. Proc. Soc. Exp. Biol. Med 127:820–23
     [Google Scholar]
  176. 176. 
    Wormley FL, Perfect JR, Steele C, Cox GM 2007. Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infect. Immun. 75:1453–62
     [Google Scholar]
  177. 177. 
    Xu JP, Vilgalys R, Mitchell TG 2000. Multiple gene genealogies reveal recent dispersion and hybridization in the human pathogenic fungus Cryptococcus neoformans. Mol. Ecol 9:1471–81
     [Google Scholar]
  178. 178. 
    Xu JP, Wang PF. 2015. Mitochondrial inheritance in basidiomycete fungi. Fungal Biol. Rev. 29:209–19
     [Google Scholar]
  179. 179. 
    Xu X, Lin J, Zhao Y, Kirkman E, So YS et al. 2017. Glucosamine stimulates pheromone-independent dimorphic transition in Cryptococcus neoformans by promoting Crz1 nuclear translocation. PLOS Genet 13:e1006982
     [Google Scholar]
  180. 180. 
    Yan Z, Hull CM, Sun S, Heitman J, Xu JP 2007. The mating type-specific homeodomain genes SXI1α and SXI2a coordinately control uniparental mitochondrial inheritance in Cryptococcus neoformans. Curr. Genet 51:187–95
     [Google Scholar]
  181. 181. 
    Yan Z, Li XG, Xu JP 2002. Geographic distribution of mating type alleles of Cryptococcus neoformans in four areas of the United States. J. Clin. Microbiol. 40:965–72
     [Google Scholar]
  182. 182. 
    Yan Z, Xu JP. 2003. Mitochondria are inherited from the MATa parent in crosses of the basidiomycete fungus Cryptococcus neoformans. Genetics 163:1315–25
     [Google Scholar]
  183. 183. 
    Yeh YL, Lin Y, Su BJ, Shen W 2009. A screening for suppressor mutants reveals components involved in the blue light-inhibited sexual filamentation in Cryptococcus neoformans. Fungal Genet. Biol 46:42–54
     [Google Scholar]
  184. 184. 
    Zaragoza O, Garcia-Rodas R, Nosanchuk JD, Cuenca-Estrella M, Rodriguez-Tudela JL, Casadevall A 2010. Fungal cell gigantism during mammalian infection. PLOS Pathog 6:e1000945
     [Google Scholar]
  185. 185. 
    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 68:133–216
     [Google Scholar]
  186. 186. 
    Zhai B, Wozniak KL, Masso-Silva J, Upadhyay S, Hole C et al. 2015. Development of protective inflammation and cell-mediated immunity against Cryptococcus neoformans after exposure to hyphal mutants. mBio 6:e01433–15
     [Google Scholar]
  187. 187. 
    Zhai B, Zhu P, Foyle D, Upadhyay S, Idnurm A, Lin X 2013. Congenic strains of the filamentous form of Cryptococcus neoformans for studies of fungal morphogenesis and virulence. Infect. Immun. 81:2626–37
     [Google Scholar]
  188. 188. 
    Zhao Y, Upadhyay S, Lin X 2018. PAS domain protein Pas3 interacts with the chromatin modifier Bre1 in regulating cryptococcal morphogenesis. mBio 9:e02135–18
     [Google Scholar]
  189. 189. 
    Zhao Y, Wang Y, Du M, Yang E, Upadhyay S et al. 2019. Unisexual reproduction occurs in the global human pathogen Cryptococcus neoformans during infection Presented at 30th Fungal Genetics Conference Pacific Grove, CA: http://conferences.genetics-gsa.org/fungal/2019/index
  190. 190. 
    Zhu P, Zhai B, Lin X, Idnurm A 2013. Congenic strains for genetic analysis of virulence traits in Cryptococcus gattii. Infect. Immun 81:2616–25
     [Google Scholar]
  191. 191. 
    Zimmer BL, Hempel HO, Goodman NL 1983. Pathogenicity of the hyphae of Filobasidiella neoformans. Mycopathologia 81:107–10
     [Google Scholar]
/content/journals/10.1146/annurev-micro-020518-120210
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Life Cycle of Cryptococcus neoformans
Annual Review of Microbiology 73, 17 (2019); https://doi.org/10.1146/annurev-micro-020518-120210
/content/journals/10.1146/annurev-micro-020518-120210
/content/journals/10.1146/annurev-micro-020518-120210
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Supplemental Material

Supplementary Data

  • Supplemental Video 1. Cryptococcal cells transition from the yeast form to the hyphal form. The expression of ZNF2 of this PCTR4-2ZNF2 strain is controlled by the promoter of the copper transporter CTR4. The strain was incubated under the ZNF2-inducing condition (YPD+BCS liquid) and monitored overtime with an imaging reader Cytation 5.

    Supplemental Video 2. Cryptococcal hyphal cells bud off yeast cells from hypha tips or septa. Hyphae of the PCTR4-2ZNF2 strain were incubated under the ZNF2-suppressing condition (YPD+ Cu2+ liquid) and monitored over time with Cytation 5.

  • Article Type: Review Article

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