A Diverse Population of Molecular Type VGIII in Southern Californian HIV/AIDS Patients
Cryptococcus gattii infections in southern California have been reported in patients with HIV/AIDS. In this study, we examined the molecular epidemiology, population structure, and virulence attributes of isolates collected from HIV/AIDS patients in Los Angeles County, California. We show that these isolates consist almost exclusively of VGIII molecular type, in contrast to the VGII molecular type isolates causing the North American Pacific Northwest outbreak. The global VGIII population structure can be divided into two molecular groups, VGIIIa and VGIIIb. Isolates from the Californian patients are virulent in murine and macrophage models of infection, with VGIIIa significantly more virulent than VGIIIb. Several VGIII isolates are highly fertile and produce abundant sexual spores that may serve as infectious propagules. The a and α VGIII MAT locus alleles are largely syntenic with limited rearrangements compared to the known VGI (a/α) and VGII (α) MAT loci, but each has unique characteristics including a distinct deletion flanking the 5′ VGIII MATa alleles and the α allele is more heterogeneous than the a allele. Our studies indicate that C. gattii VGIII is endemic in southern California, with other isolates originating from the neighboring regions of Mexico, and in rarer cases from Oregon and Washington state. Given that >1,000,000 cases of cryptococcal infection and >620,000 attributable mortalities occur annually in the context of the global AIDS pandemic, our findings suggest a significant burden of C. gattii may be unrecognized, with potential prognostic and therapeutic implications. These results signify the need to classify pathogenic Cryptococcus cases and highlight possible host differences among the C. gattii molecular types influencing infection of immunocompetent (VGI/VGII) vs. immunocompromised (VGIII/VGIV) hosts.
Vyšlo v časopise:
A Diverse Population of Molecular Type VGIII in Southern Californian HIV/AIDS Patients. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002205
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002205
Souhrn
Cryptococcus gattii infections in southern California have been reported in patients with HIV/AIDS. In this study, we examined the molecular epidemiology, population structure, and virulence attributes of isolates collected from HIV/AIDS patients in Los Angeles County, California. We show that these isolates consist almost exclusively of VGIII molecular type, in contrast to the VGII molecular type isolates causing the North American Pacific Northwest outbreak. The global VGIII population structure can be divided into two molecular groups, VGIIIa and VGIIIb. Isolates from the Californian patients are virulent in murine and macrophage models of infection, with VGIIIa significantly more virulent than VGIIIb. Several VGIII isolates are highly fertile and produce abundant sexual spores that may serve as infectious propagules. The a and α VGIII MAT locus alleles are largely syntenic with limited rearrangements compared to the known VGI (a/α) and VGII (α) MAT loci, but each has unique characteristics including a distinct deletion flanking the 5′ VGIII MATa alleles and the α allele is more heterogeneous than the a allele. Our studies indicate that C. gattii VGIII is endemic in southern California, with other isolates originating from the neighboring regions of Mexico, and in rarer cases from Oregon and Washington state. Given that >1,000,000 cases of cryptococcal infection and >620,000 attributable mortalities occur annually in the context of the global AIDS pandemic, our findings suggest a significant burden of C. gattii may be unrecognized, with potential prognostic and therapeutic implications. These results signify the need to classify pathogenic Cryptococcus cases and highlight possible host differences among the C. gattii molecular types influencing infection of immunocompetent (VGI/VGII) vs. immunocompromised (VGIII/VGIV) hosts.
Zdroje
1. CasadevallAPerfectJ 1998 Cryptococcus neoformans Washington DC. ASM Press
2. CarlileMWatkinsonSGoodayG 2001 The Fungi London Academic Press 588
3. PerfectJR 1989 Cryptococcosis. Infect Dis Clin North Am 3 77 102
4. Kwon-ChungKJBennettJE 1984 High prevalence of Cryptococcus neoformans var. gattii in tropical and subtropical regions. Zentralbl Bakteriol Mikrobiol Hyg [A] 257 213 218
5. SorrellTC 2001 Cryptococcus neoformans variety gattii. Med Mycol 39 155 168
6. IqbalNDebessEEWohrleRSunBNettRJ 2009 Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii from the Pacific Northwest of the United States. J Clin Microbiol 48 539 544
7. ByrnesEJ3rdBildfellRJFrankSAMitchellTGMarrKA 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
8. Kwon-ChungKJBennettJE 1984 Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol 120 123 130
9. KiddSEHagenFTscharkeRLHuynhMBartlettKH 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. ByrnesEJ3rdLiWLewitYMaHVoelzK 2010 Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 6 e1000850
11. SpringerDJChaturvediV 2010 Projecting global occurrence of Cryptococcus gattii. Emerg Infect Dis 16 14 20
12. CDC 2010 Emergence of Cryptococcus gattii– Pacific Northwest, 2004–2010. MMWR Morb Mortal Wkly Rep 59 865 868
13. Kwon-ChungKJVarmaA 2006 Do major species concepts support one, two or more species within Cryptococcus neoformans? FEMS Yeast Res 6 574 587
14. BoversMHagenFKuramaeEEBoekhoutT 2008 Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multi-locus sequence typing. Fungal Genet Biol 45 400 421
15. BoekhoutTTheelenBDiazMFellJWHopWC 2001 Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology 147 891 907
16. FraserJAGilesSSWeninkECGeunes-BoyerSGWrightJR 2005 Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature 437 1360 1364
17. ByrnesEJ3rdHeitmanJ 2009 Cryptococcus gattii outbreak expands into the Northwestern United States with fatal consequences. F1000 Biology Reports 1 62
18. LitvintsevaAPThakurRRellerLBMitchellTG 2005 Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in Sub-Saharan Africa. J Infect Dis 192 888 892
19. ParkBJWannemuehlerKAMarstonBJGovenderNPappasPG 2009 Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23 525 530
20. BogaertsJTaelmanHBatungwanayoJVan de PerrePSwinneD 1993 Two cases of HIV-associated cryptococcosis due to the variety gattii in Rwanda. Trans R Soc Trop Med Hyg 87 63 64
21. Castanon-OlivaresLRLopez-MartinezRBarriga-AnguloGRios-RosasC 1997 Crytococcus neoformans var. gattii in an AIDS patient: first observation in Mexico. J Med Vet Mycol 35 57 59
22. ChaturvediSDyavaiahMLarsenRAChaturvediV 2005 Cryptococcus gattii in AIDS patients, southern California. Emerg Infect Dis 11 1686 1692
23. CokerRJ 1992 Cryptococcal infection in AIDS. Int J STD AIDS 3 168 172
24. FernandesOPassosXSSouzaLKMirandaATCerqueiraCH 2003 In vitro susceptibility characteristics of Cryptococcus neoformans varieties from AIDS patients in Goiania, Brazil. Mem Inst Oswaldo Cruz 98 839 841
25. Kapend'aKKomicheloKSwinneDVandepitteJ 1987 Meningitis due to Cryptococcus neoformans biovar gattii in a Zairean AIDS patient. Eur J Clin Microbiol 6 320 321
26. KarstaedtASCrewe-BrownHHDromerF 2002 Cryptococcal meningitis caused by Cryptococcus neoformans var. gattii, serotype C, in AIDS patients in Soweto, South Africa. Med Mycol 40 7 11
27. Lindenberg AdeSChangMRPaniagoAMLazera MdosSMoncadaPM 2008 Clinical and epidemiological features of 123 cases of cryptococcosis in Mato Grosso do Sul, Brazil. Rev Inst Med Trop Sao Paulo 50 75 78
28. RozenbaumRGoncalvesAJWankeBVieiraW 1990 Cryptococcus neoformans var. gattii in a Brazilian AIDS patients. Mycopathologia 112 33 34
29. SeatonRAWembriJPArmstrongPOmbigaJNaraqiS 1996 Symptomatic human immunodeficiency virus (HIV) infection in Papua New Guinea. Aust N Z J Med 26 783 788
30. SteeleKTThakurRNthobatsangRSteenhoffAPBissonGP 2010 In-hospital mortality of HIV-infected cryptococcal meningitis patients with C. gattii and infection in Gaborone, Botswana. Med Mycol 48 1112 1115
31. OlivaresLRMartinezKMCruzRMRiveraMAMeyerW 2009 Genotyping of Mexican Cryptococcus neoformans and C. gattii isolates by PCR-fingerprinting. Med Mycol 1 9
32. FraserJASubaranRLNicholsCBHeitmanJ 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. SukroongreungSKitiniyomKNilakulCTantimavanichS 1998 Pathogenicity of basidiospores of Filobasidiella neoformans var. neoformans. Med Mycol 36 419 424
34. VelagapudiRHsuehYPGeunes-BoyerSWrightJRHeitmanJ 2009 Spores as infectious propagules of Cryptococcus neoformans. Infect Immun 77 4345 4355
35. SaulNKrockenbergerMCarterD 2008 Evidence of recombination in mixed-mating-type and alpha-only populations of Cryptococcus gattii sourced from single eucalyptus tree hollows. Eukaryot Cell 7 727 734
36. CampbellLTCurrieBJKrockenbergerMMalikRMeyerW 2005 Clonality and recombination in genetically differentiated subgroups of Cryptococcus gattii. Eukaryot Cell 4 1403 1409
37. GilesSSDagenaisTRBottsMRKellerNPHullCM 2009 Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans. Infect Immun 77 3491 3500
38. CampbellLTFraserJANicholsCBDietrichFSCarterD 2005 Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity. Eukaryot Cell 4 1410 1419
39. HeitmanJ 2006 Sexual reproduction and the evolution of microbial pathogens. Curr Biol 16 711 725
40. Kwon-ChungKJ 1976 Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68 821 833
41. Kwon-ChungKJ 1976 A new species of Filobasidiella, the sexual state of Cryptococcus neoformans B and C serotypes. Mycologia 68 943 946
42. CampbellLTCarterDA 2006 Looking for sex in the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii. FEMS Yeast Res 6 588 598
43. HeitmanJ 2010 Evolution of eukaryotic microbial pathogens via covert sexual reproduction. Cell Host Microbe 8 86 99
44. LengelerKBFoxDSFraserJAAllenAForresterK 2002 Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryot Cell 1 704 718
45. HsuehYPFraserJAHeitmanJ 2008 Transitions in sexuality: recapitulation of an ancestral tri- and tetrapolar mating system in Cryptococcus neoformans. Eukaryot Cell 7 1847 1855
46. FraserJAStajichJETarchaEJColeGTInglisDO 2007 Evolution of the mating type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii. Eukaryot Cell 6 622 629
47. FraserJAHeitmanJ 2003 Fungal mating-type loci. Curr Biol 13 R792 795
48. FraserJADiezmannSSubaranRLAllenALengelerKB 2004 Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms. PLoS Biol 2 e384
49. MaHHagenFStekelDJJohnstonSASionovE 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
50. ChengPYShamAKronstadJW 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
51. NielsenKCoxGMWangPToffalettiDLPerfectJR 2003 Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect Immun 71 4831 4841
52. Kwon-ChungKJEdmanJCWickesBL 1992 Genetic association of mating types and virulence in Cryptococcus neoformans. Infect Immun 60 602 605
53. BoversMHagenFKuramaeEEDiazMRSpanjaardL 2006 Unique hybrids between the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii. FEMS Yeast Res 6 599 607
54. CarterDCampbellLTSaulNKrockenbergerM 2010 Sexual reproduction of Cryptococcus gattii: a population genetics perspective. HeitmanJKozelTKwon-ChungJPerfectJRCasadevallA Cryptococcus: From human pathogen to model yeast ASM Press
55. CarterDSaulNCampbellLTTienBKrockenbergerM 2007 Sex in natural populations of C. gattii. HeitmanJKronstadJWTaylorJCasseltonL 477 488 Sex in Fungi: Molecular Determination and Evolutionary Implications: ASM Press
56. GiraudTGladieuxPByrnesEJIIIFisherMAguiletaG 2011 Epidemiology and evolution of fungal pathogens in plants and animals. TibayrencM Genetics and Evolution of Infectious Diseases New York Elsevier 59 106
57. KiddSEGuoHBartlettKHXuJKronstadJW 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
58. LindbergJHagenFLaursenAStenderupJBoekhoutT 2007 Cryptococcus gattii risk for tourists visiting Vancouver Island, Canada. Emerg Infect Dis 13 178 179
59. DattaKBartlettKHBaerRByrnesEGalanisE 2009 Spread of Cryptococcus gattii into Pacific Northwest region of the United States. Emerg Infect Dis 15 1185 1191
60. OkamotoKHatakeyamaSItoyamaSNukuiYYoshinoY 2010 Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis 16 1155 1157
61. HagenFAssenSVLuijckxGJBoekhoutTKampingaGA 2009 Activated dormant Cryptococcus gattii infection in a Dutch tourist who visited Vancouver Island (Canada): a molecular epidemiological approach. Med Mycol 48 528 531
62. GeorgiASchneemannMTintelnotKCalligaris-MaibachRCMeyerS 2009 Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months after exposure. Infection 37 370 373
63. MacDougallLKiddSEGalanisEMakSLeslieMJ 2007 Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis 13 42 50
64. LitiGBartonDBLouisEJ 2006 Sequence diversity, reproductive isolation and species concepts in Saccharomyces. Genetics 174 839 850
65. Le GacMHoodMEFournierEGiraudT 2007 Phylogenetic evidence of host-specific cryptic species in the anther smut fungus. Evolution 61 15 26
66. KavanaughLAFraserJADietrichFS 2006 Recent evolution of the human pathogen Cryptococcus neoformans by intervarietal transfer of a 14-gene fragment. Mol Biol Evol 23 1879 1890
67. NeafseyDEBarkerBMSharptonTJStajichJEParkDJ 2010 Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control. Genome Res 20 938 946
68. OkagakiLHStrainAKNielsenJNCharlierCBaltesNJ 2010 Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathog 6 e1000953
69. NgamskulrungrojPSorrellTCChindampornAChaiprasertAPoonwanN 2008 Association between fertility and molecular sub-type of global isolates of Cryptococcus gattii molecular type VGII. Med Mycol 1 9
70. BakkerenGKamperJSchirawskiJ 2008 Sex in smut fungi: Structure, function and evolution of mating-type complexes. Fungal Genet Biol 45 Suppl 1 S15 21
71. NielsenKCoxGMLitvintsevaAPMylonakisEMalliarisSD 2005 Cryptococcus neoformans alpha strains preferentially disseminate to the central nervous system during coinfection. Infect Immun 73 4922 4933
72. NielsenKHeitmanJ 2007 Sex and virulence of human pathogenic fungi. Adv Genet 57 143 173
73. DanielsKJSrikanthaTLockhartSRPujolCSollDR 2006 Opaque cells signal white cells to form biofilms in Candida albicans. EMBO J 25 2240 2252
74. SahniNYiSDanielsKJHuangGSrikanthaT 2010 Tec1 mediates the pheromone response of the white phenotype of Candida albicans: insights into the evolution of new signal transduction pathways. PLoS Biol 8 e1000363
75. YiSSahniNPujolCDanielsKJSrikanthaT 2009 A Candida albicans-specific region of the alpha-pheromone receptor plays a selective role in the white cell pheromone response. Mol Microbiol 71 925 947
76. ZhaoRDanielsKJLockhartSRYeaterKMHoyerLL 2005 Unique aspects of gene expression during Candida albicans mating and possible G(1) dependency. Eukaryot Cell 4 1175 1190
77. XueCTadaYDongXHeitmanJ 2007 The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. Cell Host Microbe 1 263 273
78. PapageorgiouIGournasCVlantiAAmillisSPantazopoulouA 2008 Specific interdomain synergy in the UapA transporter determines its unique specificity for uric acid among NAT carriers. J Mol Biol 382 1121 1135
79. DiallinasGGorfinkielLArstHNJrCecchettoGScazzocchioC 1994 Genetic and molecular characterisation of purine permease genes of Aspergillus nidulans reveals a novel family of transporters conserved in prokaryotes and eukaryotes. Folia Microbiol (Praha) 39 513 514
80. DiallinasGScazzocchioC 1989 A gene coding for the uric acid-xanthine permease of Aspergillus nidulans: inactivational cloning, characterization, and sequence of a cis-acting mutation. Genetics 122 341 350
81. ErbsPExingerFJundR 1997 Characterization of the Saccharomyces cerevisiae FCY1 gene encoding cytosine deaminase and its homologue FCA1 of Candida albicans. Curr Genet 31 1 6
82. WhelanWL 1987 The genetic basis of resistance to 5-fluorocytosine in Candida species and Cryptococcus neoformans. Crit Rev Microbiol 15 45 56
83. HsuehYPIdnurmAHeitmanJ 2006 Recombination hotspots flank the Cryptococcus mating-type locus: implications for the evolution of a fungal sex chromosome. PLoS Genet 2 e184
84. FindleyKRodriguez-CarresMMetinBKroissJFonsecaA 2009 Phylogeny and phenotypic characterization of pathogenic Cryptococcus species and closely related saprobic taxa in the Tremellales. Eukaryot Cell 8 353 361
85. MetinBFindleyKHeitmanJ 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
86. McClellandEEPerrineWTPottsWKCasadevallA 2005 Relationship of virulence factor expression to evolved virulence in mouse-passaged Cryptococcus neoformans lines. Infect Immun 73 7047 7050
87. MaidenMCBygravesJAFeilEMorelliGRussellJE 1998 Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95 3140 3145
88. ByrnesEJ3rdBildfellRJDearingPLValentineBAHeitmanJ 2009 Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak. J Vet Diagn Invest 21 133 136
89. ByrnesEJ3rdLiWLewitYPerfectJRCarterDA 2009 First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen. PLoS One 4 e5851
90. MeyerWAanensenDMBoekhoutTCogliatiMDiazMR 2009 Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol 47 561 570
91. AltschulSFMaddenTLSchafferAAZhangJZhangZ 1997 Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 3389 3402
92. LarkinMABlackshieldsGBrownNPChennaRMcGettiganPA 2007 Clustal W and Clustal X version 2.0. Bioinformatics 23 2947 2948
93. GuindonSDelsucFDufayardJFGascuelO 2009 Estimating maximum likelihood phylogenies with PhyML. Methods Mol Biol 537 113 137
94. ClementMPosadaDCrandallKA 2000 TCS: a computer program to estimate gene genealogies. Mol Ecol 9 1657 1659
95. EwingBGreenP 1998 Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 8 186 194
96. EwingBHillierLWendlMCGreenP 1998 Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8 175 185
97. NarasipuraSDChaturvediVChaturvediS 2005 Characterization of Cryptococcus neoformans variety gattii SOD2 reveals distinct roles of the two superoxide dismutases in fungal biology and virulence. Mol Microbiol 55 1782 1800
98. MaHCroudaceJELammasDAMayRC 2006 Expulsion of live pathogenic yeast by macrophages. Curr Biol 16 2156 2160
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2011 Číslo 9
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Hostile Takeover by : Reorganization of Parasite and Host Cell Membranes during Liver Stage Egress
- HTLV-1 Propels Thymic Human T Cell Development in “Human Immune System” Rag2 gamma c Mice
- Exploiting and Subverting Tor Signaling in the Pathogenesis of Fungi, Parasites, and Viruses
- A Viral Ubiquitin Ligase Has Substrate Preferential SUMO Targeted Ubiquitin Ligase Activity that Counteracts Intrinsic Antiviral Defence