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Transmission of Hypervirulence Traits via Sexual Reproduction within and between Lineages of the Human Fungal Pathogen


Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded history. The high virulence of outbreak strains is closely linked to the ability of the pathogen to undergo rapid mitochondrial tubularisation and proliferation following engulfment by host phagocytes. Most outbreaks spread by geographic expansion across suitable niches, but it is known that genetic re-assortment and hybridisation can also lead to rapid range and host expansion. In the context of C. gattii, however, the likelihood of virulence traits associated with the outbreak lineages spreading to other lineages via genetic exchange is currently unknown. Here we address this question by conducting outgroup crosses between distantly related C. gattii lineages (VGII and VGIII) and ingroup crosses between isolates from the same molecular type (VGII). Systematic phenotypic characterisation shows that virulence traits are transmitted to outgroups infrequently, but readily inherited during ingroup crosses. In addition, we observed higher levels of biparental (as opposed to uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this species and provide evidence for mitochondrial recombination following mating. Taken together, our data suggest that hypervirulence can spread among the C. gattii lineages VGII and VGIII, potentially creating novel hypervirulent genotypes, and that current models of uniparental mitochondrial inheritance in the Cryptococcus genus may not be universal.


Vyšlo v časopise: Transmission of Hypervirulence Traits via Sexual Reproduction within and between Lineages of the Human Fungal Pathogen. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003771
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003771

Souhrn

Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded history. The high virulence of outbreak strains is closely linked to the ability of the pathogen to undergo rapid mitochondrial tubularisation and proliferation following engulfment by host phagocytes. Most outbreaks spread by geographic expansion across suitable niches, but it is known that genetic re-assortment and hybridisation can also lead to rapid range and host expansion. In the context of C. gattii, however, the likelihood of virulence traits associated with the outbreak lineages spreading to other lineages via genetic exchange is currently unknown. Here we address this question by conducting outgroup crosses between distantly related C. gattii lineages (VGII and VGIII) and ingroup crosses between isolates from the same molecular type (VGII). Systematic phenotypic characterisation shows that virulence traits are transmitted to outgroups infrequently, but readily inherited during ingroup crosses. In addition, we observed higher levels of biparental (as opposed to uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this species and provide evidence for mitochondrial recombination following mating. Taken together, our data suggest that hypervirulence can spread among the C. gattii lineages VGII and VGIII, potentially creating novel hypervirulent genotypes, and that current models of uniparental mitochondrial inheritance in the Cryptococcus genus may not be universal.


Zdroje

1. ChengPY, ShamA, KronstadJW (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: 4284–4294.

2. LuiG, LeeN, IpM, ChoiKW, TsoYK, et al. (2006) Cryptococcosis in apparently immunocompetent patients. QJM 99: 143–151.

3. IdnurmA, BahnYS, NielsenK, LinX, FraserJA, et al. (2005) Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat Rev Microbiol 3: 753–764.

4. KronstadJW, AttarianR, CadieuxB, ChoiJ, D'SouzaCA, et al. (2011) Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box. Nat Rev Microbiol 9: 193–203.

5. ByrnesEJ (2011) A diverse population of Cryptococcus gattii molecular type VGIII in southern Californian HIV/AIDS patients. PLoS Pathog 7: e1002205.

6. ChenJ, VarmaA, DiazMR, LitvintsevaAP, WollenbergKK, et al. (2008) Cryptococcus neoformans strains and infection in apparently immunocompetent patients, China. Emerg Infect Dis 14: 755–762.

7. BartlettKH, KiddSE, KronstadJW (2008) The emergence of Cryptococcus gattii in British Columbia and the Pacific Northwest. Curr Infect Dis Rep 10: 58–65.

8. KiddSE, BachPJ, HingstonAO, MakS, ChowY, et al. (2007) Cryptococcus gattii dispersal mechanisms, British Columbia, Canada. Emerg Infect Dis 13: 51–57.

9. KiddSE, HagenF, TscharkeRL, HuynhM, BartlettKH, et al. (2004) A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci U S A 101: 17258–17263.

10. ByrnesEJ, HeitmanJ (2009) Cryptococcus gattii outbreak expands into the Northwestern United States with fatal consequences. F1000 Biol Reports 1: 62.

11. ByrnesEJ (2010) Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 6: e1000850.

12. ByrnesEJ (2009) First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen. PLoS ONE 4: e5851.

13. DattaK, BartlettKH, BaerR, ByrnesE, GalanisE, et al. (2009) Spread of Cryptococcus gattii into Pacific Northwest region of the United States. Emerg Infect Dis 15: 1185–1191.

14. ByrnesEJ (2011) Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals. Microbes Infect 13: 895–907.

15. GalanisE, MacdougallL, KiddS, MorshedM (2010) Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999–2007. Emerg Infect Dis 16: 251–257.

16. PatrickS, TurabelidzeG, YatesK, MyersA, NasciR, et al. (2010) Emergence of Cryptococcus gattii - Pacific Northwest, 2004–2010. MMWR Morb Mortal Wkly Rep 59: 865–868.

17. MarrKA (2012) Cryptococcus gattii as an important fungal pathogen of western North America. Expert Rev Anti Infect Ther 10: 637–643.

18. ByrnesEJ (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: 1081–1086.

19. MoreraN, Juan-SallésC, TorresJM, AndreuM, SánchezM, et al. (2011) Cryptococcus gattii infection in a Spanish pet ferret (Mustela putorius furo) and asymptomatic carriage in ferrets and humans from its environment. Medical Mycology 49: 779–784.

20. KiddSE, GuoH, BartlettKH, XuJ, KronstadJW (2005) Comparative gene genealogies indicate that two clonal lineages of Cryptococcus gattii in British Columbia resemble strains from other geographical areas. Eukaryot Cell 4: 1629–1638.

21. MaH, HagenF, StekelDJ, JohnstonSA, SionovE, et al. (2009) The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation. Proc Natl Acad Sci U S A 106: 12980–12985.

22. HeitmanJ (2010) Evolution of eukaryotic microbial pathogens via covert sexual reproduction. Cell Host Microbe 8: 86–99.

23. GriggME, BonnefoyS, HehlAB, SuzukiY, BoothroydJC (2001) Success and virulence in Toxoplasma as the result of sexual recombination between two distinct ancestries. Science 294: 161–165.

24. FraserJA, GilesSS, WeninkEC, Geunes-BoyerSG, WrightJR, et al. (2005) Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature 437: 1360–1364.

25. HeitmanJ (2006) Sexual reproduction and the evolution of microbial pathogens. Curr Biol 16: R711–725.

26. WendteJM, MillerMA, LambournDM, MagargalSL, JessupDA, et al. (2011) Self-mating in the definitive host potentiates clonal outbreaks of the apicomplexan parasites Sarcocystis neurona and Toxoplasma gondii. PLoS Genet 6: e1001261.

27. ToffalettiDL, NielsenK, DietrichF, HeitmanJ, PerfectJR (2004) Cryptococcus neoformans mitochondrial genomes from serotype A and D strains do not influence virulence. Curr Genet 46: 193–204.

28. XuJ, AliRY, GregoryDA, AmickD, LambertSE, et al. (2000) Uniparental mitochondrial transmission in sexual crosses in Cryptococcus neoformans. Curr Microbiol 40: 269–273.

29. YanZ, XuJ (2003) Mitochondria are inherited from the MATa parent in crosses of the basidiomycete fungus Cryptococcus neoformans. Genetics 163: 1315–1325.

30. NgamskulrungrojP, SorrellTC, ChindampornA, ChaiprasertA, PoonwanN, et al. (2008) Association between fertility and molecular sub-type of global isolates of Cryptococcus gattii molecular type VGII. Med Mycol 46: 665–673.

31. HallidayCL, CarterDA (2003) Clonal reproduction and limited dispersal in an environmental population of Cryptococcus neoformans var. gattii isolates from Australia. J Clin Microbiol 41: 703–711.

32. FraserJA, SubaranRL, NicholsCB, HeitmanJ (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: 1036–1045.

33. BoversM, HagenF, KuramaeEE, BoekhoutT (2008) Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multi-locus sequence typing. Fungal Genet Biol 45: 400–421.

34. NgamskulrungrojP, GilgadoF, FaganelloJ, LitvintsevaAP, LealAL, et al. (2009) Genetic diversity of the Cryptococcus species complex suggests that Cryptococcus gattii deserves to have varieties. PLoS One 4: e5862.

35. ChambersSR, HunterN, LouisEJ, BortsRH (1996) The mismatch repair system reduces meiotic homeologous recombination and stimulates recombination-dependent chromosome loss. Mol Cell Biol 16: 6110–6120.

36. HunterN, ChambersSR, LouisEJ, BortsRH (1996) The mismatch repair system contributes to meiotic sterility in an interspecific yeast hybrid. EMBO J 15: 1726–1733.

37. RayssiguierC, ThalerDS, RadmanM (1989) The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 342: 396–401.

38. XuJ, YanZ, GuoH (2009) Divergence, hybridization, and recombination in the mitochondrial genome of the human pathogenic yeast Cryptococcus gattii. Mol Ecol 18: 2628–2642.

39. YanZ, HullCM, HeitmanJ, SunS, XuJ (2004) SXI1alpha controls uniparental mitochondrial inheritance in Cryptococcus neoformans. Curr Biol 14: R743–744.

40. Heitman J, Kozel TR, Kwon-Chung J, Perfect JR, Casadevall A (2011) Cryptococcus: from human pathogen to model yeast. Washington, DC: ASM Press.

41. LengelerKB, CoxGM, HeitmanJ (2001) Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Infect Immun 69: 115–122.

42. Kwon-ChungKJ, ChangYC (2012) Aneuploidy and drug resistance in pathogenic fungi. PLoS Pathog 8: e1003022.

43. FraserJA, HuangJC, Pukkila-WorleyR, AlspaughJA, MitchellTG, et al. (2005) Chromosomal translocation and segmental duplication in Cryptococcus neoformans. Eukaryot Cell 4: 401–406.

44. SionovE, LeeH, ChangYC, Kwon-ChungKJ (2010) Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog 6: e1000848.

45. SebastianiF, BarberioC, CasaloneE, CavalieriD, PolsinelliM (2002) Crosses between Saccharomyces cerevisiae and Saccharomyces bayanus generate fertile hybrids. Res Microbiol 153: 53–58.

46. WangX, HsuehYP, LiW, FloydA, SkalskyR, et al. (2010) Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Genes Dev 24: 2566–2582.

47. SkosirevaI, JamesTY, SunS, XuJ (2010) Mitochondrial inheritance in haploid x non-haploid crosses in Cryptococcus neoformans. Curr Genet 56: 163–176.

48. EphrussiB, de Margerie-HottinguerH, RomanH (1955) Suppressiveness: A new factor in the genetic determinism of the synthesis of respiratory enzymes in Yeast. Proc Natl Acad Sci U S A 41: 1065–1071.

49. de ZamaroczyM, MarottaR, Faugeron-FontyG, GoursotR, ManginM, et al. (1981) The origins of replication of the yeast mitochondrial genome and the phenomenon of suppressivity. Nature 292: 75–78.

50. BlancH, DujonB (1980) Replicator regions of the yeast mitochondrial DNA responsible for suppressiveness. Proc Natl Acad Sci U S A 77: 3942–3946.

51. NielsenK, CoxGM, WangP, ToffalettiDL, PerfectJR, et al. (2003) Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect Immun 71: 4831–4841.

52. BoversM, HagenF, KuramaeEE, BoekhoutT (2009) Promiscuous mitochondria in Cryptococcus gattii. FEMS Yeast Res 9: 489–503.

53. MeyerW, AanensenDM, BoekhoutT, CogliatiM, DiazMR, et al. (2009) Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol 1–14.

54. LinX, LitvintsevaAP, NielsenK, PatelS, FloydA, et al. (2007) Alpha AD alpha hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness. PLoS Genet 3: 1975–1990.

55. DettmanJR, JacobsonDJ, TurnerE, PringleA, TaylorJW (2003) Reproductive isolation and phylogenetic divergence in Neurospora: comparing methods of species recognition in a model eukaryote. Evolution 57: 2721–2741.

56. Le GacM, HoodME, GiraudT (2007) Evolution of reproductive isolation within a parasitic fungal species complex. Evolution 61: 1781–1787.

57. BoekhoutT, TheelenB, DiazM, FellJW, HopWC, et al. (2001) Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology 147: 891–907.

58. LinX, PatelS, LitvintsevaAP, FloydA, MitchellTG, et al. (2009) Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating. PLoS Pathog 5: e1000283.

59. BoversM, HagenF, KuramaeEE, DiazMR, SpanjaardL, et al. (2006) Unique hybrids between the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii. FEMS Yeast Res 6: 599–607.

60. LitvintsevaAP, KestenbaumL, VilgalysR, MitchellTG (2005) Comparative analysis of environmental and clinical populations of Cryptococcus neoformans. J Clin Microbiol 43: 556–564.

61. AminnejadM, DiazM, ArabatzisM, CastanedaE, LazeraM, et al. (2012) Identification of novel hybrids between Cryptococcus neoformans var. grubii VNI and Cryptococcus gattii VGII. Mycopathologia 173: 337–346.

62. BoversM, HagenF, KuramaeEE, HoogveldHL, DromerF, et al. (2008) AIDS patient death caused by novel Cryptococcus neoformans x C. gattii hybrid. Emerg Infect Dis 14: 1105–1108.

63. GyawaliR, LinX (2011) Mechanisms of uniparental mitochondrial DNA inheritance in Cryptococcus neoformans. Mycobiology 39: 235–242.

64. WangL, LinX (2011) Mechanisms of unisexual mating in Cryptococcus neoformans. Fungal Genet Biol 48: 651–660.

65. YanZ, SunS, ShahidM, XuJ (2007) Environment factors can influence mitochondrial inheritance in the fungus Cryptococcus neoformans. Fungal Genet Biol 44: 315–322.

66. YanZ, HullCM, SunS, HeitmanJ, XuJ (2007) The mating type-specific homeodomain genes SXI1alpha and SXI2a coordinately control uniparental mitochondrial inheritance in Cryptococcus neoformans. Curr Genet 51: 187–195.

67. GyawaliR, LinX (2013) Prezygotic and postzygotic control of uniparental mitochondrial DNA inheritance in Cryptococcus neoformans. mBio 4: e00112–00113.

68. ZhuP, ZhaiB, LinX, IdnurmA (2013) Congenic strains for the genetic analysis of virulence traits in Cryptococcus gattii. Infect Immun 81: 2616–2625.

69. MeeusenS, NunnariJ (2003) Evidence for a two membrane-spanning autonomous mitochondrial DNA replisome. J Cell Biol 163: 503–510.

70. WongED, WagnerJA, GorsichSW, McCafferyJM, ShawJM, et al. (2000) The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J Cell Biol 151: 341–352.

71. SesakiH, SouthardSM, YaffeMP, JensenRE (2003) Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Mol Biol Cell 14: 2342–2356.

72. SesakiH, JensenRE (1999) Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J Cell Biol 147: 699–706.

73. MaH, CroudaceJE, LammasDA, MayRC (2006) Expulsion of live pathogenic yeast by macrophages. Curr Biol 16: 2156–2160.

74. HsuehYP, IdnurmA, HeitmanJ (2006) Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome. PLoS Genet 2: e184.

75. HsuehYP, FraserJA, HeitmanJ (2008) Transitions in sexuality: recapitulation of an ancestral tri- and tetrapolar mating system in Cryptococcus neoformans. Eukaryot Cell 7: 1847–1855.

76. PitkinJW, PanaccioneDG, WaltonJD (1996) A putative cyclic peptide efflux pump encoded by the TOXA gene of the plant-pathogenic fungus Cochliobolus carbonum. Microbiology 142: 1557–1565.

77. D'SouzaCA, KronstadJW, TaylorG, WarrenR, YuenM, et al. (2011) Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. mBio 2: e00342–00310.

78. LinX, HullCM, HeitmanJ (2005) Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434: 1017–1021.

79. WickesBL, MayorgaME, EdmanU, EdmanJC (1996) Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type. Proc Natl Acad Sci U S A 93: 7327–7331.

80. VoelzK, LammasDA, MayRC (2009) Cytokine signaling regulates the outcome of intracellular macrophage parasitism by Cryptococcus neoformans. Infect Immun 77: 3450–3457.

81. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.

82. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079.

83. FarrerRA, HenkDA, MacLeanD, StudholmeDJ, FisherMC (2013) Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects. Sci Rep 3: 1512.

84. ZerbinoDR, BirneyE (2008) Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18: 821–829.

85. KurtzS, PhillippyA, DelcherAL, SmootM, ShumwayM, et al. (2004) Versatile and open software for comparing large genomes. Genome Biol 5: R12.

86. DelcherAL, KasifS, FleischmannRD, PetersonJ, WhiteO, et al. (1999) Alignment of whole genomes. Nucleic Acids Res 27: 2369–2376.

87. LangmeadB, SalzbergSL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357–359.

88. XieC, TammiMT (2009) CNV-seq, a new method to detect copy number variation using high-throughput sequencing. BMC Bioinformatics 10: 80.

89. DarlingAE, MauB, PernaNT (2010) progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS ONE 5: e11147.

90. BoekhoutT, van BelkumA, LeendersAC, VerbrughHA, MukamurangwaP, et al. (1997) Molecular typing of Cryptococcus neoformans: taxonomic and epidemiological aspects. Int J Syst Bacteriol 47: 432–442.

91. ChuckSL, SandeMA (1989) Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 321: 794–799.

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