Transcription Factors Mat2 and Znf2 Operate Cellular Circuits Orchestrating Opposite- and Same-Sex Mating in
Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex (mating) and unisexual reproduction (same-sex mating). Opposite- and same-sex mating are induced by similar environmental conditions and involve many shared components, including the conserved pheromone sensing Cpk1 MAPK signal transduction cascade that governs the dimorphic switch in C. neoformans. However, the homeodomain cell identity proteins Sxi1α/Sxi2a encoded by the mating type locus that are essential for completion of sexual reproduction following cell–cell fusion during opposite-sex mating are dispensable for same-sex mating. Therefore, identification of downstream targets of the Cpk1 MAPK pathway holds the key to understanding molecular mechanisms governing the two distinct developmental fates. Thus far, homology-based approaches failed to identify downstream transcription factors which may therefore be species-specific. Here, we applied insertional mutagenesis via Agrobacterium-mediated transformation and transcription analysis using whole genome microarrays to identify factors involved in C. neoformans differentiation. Two transcription factors, Mat2 and Znf2, were identified as key regulators of hyphal growth during same- and opposite-sex mating. Mat2 is an HMG domain factor, and Znf2 is a zinc finger protein; neither is encoded by the mating type locus. Genetic, phenotypic, and transcriptional analyses of Mat2 and Znf2 provide evidence that Mat2 is a downstream transcription factor of the Cpk1 MAPK pathway whereas Znf2 functions as a more terminal hyphal morphogenesis determinant. Although the components of the MAPK pathway including Mat2 are not required for virulence in animal models, Znf2, as a hyphal morphology determinant, is a negative regulator of virulence. Further characterization of these elements and their target circuits will reveal genes controlling biological processes central to fungal development and virulence.
Vyšlo v časopise:
Transcription Factors Mat2 and Znf2 Operate Cellular Circuits Orchestrating Opposite- and Same-Sex Mating in. PLoS Genet 6(5): e32767. doi:10.1371/journal.pgen.1000953
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000953
Souhrn
Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex (mating) and unisexual reproduction (same-sex mating). Opposite- and same-sex mating are induced by similar environmental conditions and involve many shared components, including the conserved pheromone sensing Cpk1 MAPK signal transduction cascade that governs the dimorphic switch in C. neoformans. However, the homeodomain cell identity proteins Sxi1α/Sxi2a encoded by the mating type locus that are essential for completion of sexual reproduction following cell–cell fusion during opposite-sex mating are dispensable for same-sex mating. Therefore, identification of downstream targets of the Cpk1 MAPK pathway holds the key to understanding molecular mechanisms governing the two distinct developmental fates. Thus far, homology-based approaches failed to identify downstream transcription factors which may therefore be species-specific. Here, we applied insertional mutagenesis via Agrobacterium-mediated transformation and transcription analysis using whole genome microarrays to identify factors involved in C. neoformans differentiation. Two transcription factors, Mat2 and Znf2, were identified as key regulators of hyphal growth during same- and opposite-sex mating. Mat2 is an HMG domain factor, and Znf2 is a zinc finger protein; neither is encoded by the mating type locus. Genetic, phenotypic, and transcriptional analyses of Mat2 and Znf2 provide evidence that Mat2 is a downstream transcription factor of the Cpk1 MAPK pathway whereas Znf2 functions as a more terminal hyphal morphogenesis determinant. Although the components of the MAPK pathway including Mat2 are not required for virulence in animal models, Znf2, as a hyphal morphology determinant, is a negative regulator of virulence. Further characterization of these elements and their target circuits will reveal genes controlling biological processes central to fungal development and virulence.
Zdroje
1. BanuettF
1998 Signalling in the yeasts: an informational cascade with links to the filamentous fungi. Microbiol Mol Biol Rev 62 249 274
2. DohlmanHG
SlessarevaJE
2006 Pheromone signaling pathways in yeast. Sci STKE 2006 cm6
3. SchwartzMA
MadhaniHD
2004 Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae. Annu Rev Genet 38 725 748
4. DavidsonRC
NicholsCB
CoxGM
PerfectJR
HeitmanJ
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 49 469 485
5. BardwellL
CookJG
InouyeCJ
ThornerJ
1994 Signal propagation and regulation in the mating pheromone response pathway of the yeast Saccharomyces cerevisiae. Dev Biol 166 363 379
6. LinX
2009 Cryptococcus neoformans: morphogenesis, infection, and evolution. Infection, Genetics and Evolution 9 401 416
7. AndrianopoulosA
2002 Control of morphogenesis in the human fungal pathogen Penicillium marneffei. Int J Med Microbiol 292 331 347
8. Kwon-ChungKJ
BennettJE
1992 Medical mycology Philadelphia Lea & Febiger
9. GreerDL
1978 Basidiomycetes as agents of human infections: a review. Mycopathologia 65 133 139
10. BraunBR
JohnsonAD
1997 Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277 105 109
11. CsankC
SchroppelK
LebererE
HarcusD
MohamedO
1998 Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun 66 2713 2721
12. LoHJ
KohlerJR
DiDomenicoB
LoebenbergD
CacciapuotiA
1997 Nonfilamentous C. albicans mutants are avirulent. Cell 90 939 949
13. StoldtVR
SonnebornA
LeukerCE
ErnstJF
1997 Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J 16 1982 1991
14. MarescaB
KobayashiGS
2000 Dimorphism in Histoplasma capsulatum and Blastomyces dermatitidis. Contrib Microbiol 5 201 216
15. KleinBS
TebbetsB
2007 Dimorphism and virulence in fungi. Curr Opin Microbiol 10 314 319
16. LimaRF
Santos BritoMM
SchafferGM
LimaOC
Borba CdeM
2004 Evaluation of the in vitro and in vivo dimorphism of Sporothrix schenckii, Blastomyces dermatitidis, and Paracoccidioides brasiliensis isolates after preservation in mineral oil. Can J Microbiol 50 445 449
17. DhillonNK
SharmaS
KhullerGK
2003 Signaling through protein kinases and transcriptional regulators in Candida albicans. Crit Rev Microbiol 29 259 275
18. LiuH
2002 Co-regulation of pathogenesis with dimorphism and phenotypic switching in Candida albicans, a commensal and a pathogen. Int J Med Microbiol 292 299 311
19. LopezCE
2006 Dimorphism and pathogenesis of Histoplasma capsulatum. Rev Argent Microbiol 38 235 242
20. CasadevallA
PerfectJR
1998 Cryptococcus neoformans Washington, D.C. ASM Press
21. MitchellTG
PerfectJR
1995 Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 8 515 548
22. Pukkila-WorleyR
MylonakisE
2008 Epidemiology and management of cryptococcal meningitis: developments and challenges. Expert Opin Pharmacother 9 1 10
23. ChenJ
VarmaA
DiazMR
LitvintsevaAP
WollenbergKK
2008 Cryptococcus neoformans strains and infection in apparently immunocompetent patients, China. Emerg Infect Dis 14 755 762
24. ParkBJ
Refocusing on a re-emergent disease: The current global burden of cryptococcal meningitis among persons living with HIV/AIDS; 2008; Washington, DC. Abstract M-1848
25. Kwon-ChungKJ
1975 A new genus, Filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia 67 1197 1200
26. Kwon-ChungKJ
1976 A new species of Filobasidiella, the sexual state of Cryptococcus neoformans B and C serotypes. Mycologia 68 943 946
27. McClellandCM
ChangYC
VarmaA
Kwon-ChungKJ
2004 Uniqueness of the mating system in Cryptococcus neoformans. Trends Microbiol 12 208 212
28. AlspaughJA
DavidsonRC
HeitmanJ
2000 Morphogenesis of Cryptococcus neoformans. Contrib Microbiol 5 217 238
29. IwasaM
TanabeS
KamadaT
1998 The two nuclei in the dikaryon of the homobasidiomycete Coprinus cinereus change position after each conjugate division. Fungal Genet Biol 23 110 116
30. LinX
HullCM
HeitmanJ
2005 Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434 1017 1021
31. NielsenK
CoxGM
WangP
ToffalettiDL
PerfectJR
2003 Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and a isolates. Infect Immun 71 4831 4841
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. ErkeKH
1976 Light microscopy of basidia, basidiospores, and nuclei in spores and hyphae of Filobasidiella neoformans (Cryptococcus neoformans). J Bacteriol 128 445 455
34. WickesBL
MayorgaME
EdmanU
EdmanJC
1996 Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type. Proc Natl Acad Sci USA 93 7327 7331
35. LinX
HuangJC
MitchellTG
HeitmanJ
2006 Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATa allele enhances filamentation. PLoS Genet 2 e187 doi:10.1371/journal.pgen.0020187
36. BuiT
LinX
MalikR
HeitmanJ
CarterD
2008 Isolates of Cryptococcus neoformans from infected animals reveal genetic exchange in unisexual, a mating type populations. Eukaryot Cell 7 1771 1780
37. ToddRL
HerrmannWW
1936 The life cycle of the organism causing yeast meningitis. J Bacteriol 32 89 103
38. LinX
LitvintsevaA
NielsenK
PatelS
KapadiaZ
2007 aADa hybrids of Cryptococcus neoformans: Evidence of same sex mating in nature and hybrid fitness. PLoS Genet 3 e186 doi:10.1371/journal.pgen.0030186
39. HullCM
BoilyMJ
HeitmanJ
2005 Sex-specific homeodomain proteins Sxi1a and Sxi2a coordinately regulate sexual development in Cryptococcus neoformans. Eukaryot Cell 4 526 535
40. HullCM
DavidsonRC
HeitmanJ
2002 Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1a. Genes Dev 16 3046 3060
41. ButlerG
RasmussenMD
LinMF
SantosMA
SakthikumarS
2009 Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459 657 662
42. AlbyK
SchaeferD
BennettRJ
2009 Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460 890 893
43. ReedyJL
FloydAM
HeitmanJ
2009 Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex. Curr Biol 19 891 899
44. HuangG
SrikanthaT
SahniN
YiS
SollDR
2009 CO2 regulates white-to-opaque switching in Candida albicans. Current Biology 19 1 5
45. HerskowitzI
1995 MAP kinase pathways in yeast: for mating and more. Cell 80 187 197
46. ClarkeDL
WoodleeGL
McClellandCM
SeymourTS
WickesBL
2001 The Cryptococcus neoformans STE11a gene is similar to other fungal mitogen-activated protein kinase kinase kinase (MAPKKK) genes but is mating type specific. Mol Microbiol 40 200 213
47. WangP
NicholsCB
LengelerKB
CardenasME
CoxGM
2002 Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans. Eukaryot Cell 1 257 272
48. NicholsCB
FraserJA
HeitmanJ
2004 PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Mol Biol Cell 15 4476 4489
49. GavriasV
AndrianopoulosA
GimenoCJ
TimberlakeWE
1996 Saccharomyces cerevisiae TEC1 is required for pseudohyphal growth. Mol Microbiol 19 1255 1263
50. MadhaniHD
FinkGR
1997 Combinatorial control required for the specificity of yeast MAPK signaling. Science 275 1314 1317
51. WickesBL
EdmanU
EdmanJC
1997 The Cryptococcus neoformans STE12a gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific. Mol Microbiol 26 951 960
52. YueC
CavalloLM
AlspaughJA
WangP
CoxGM
1999 The STE12a homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. Genetics 153 1601 1615
53. ChangYC
WickesBL
MillerGF
PenoyerLA
Kwon-ChungKJ
2000 Cryptococcus neoformans STE12a regulates virulence but is not essential for mating. J Exp Med 191 871 882
54. ChangYC
PenoyerLA
Kwon-ChungKJ
2001 The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Proc Natl Acad Sci U S A 98 3258 3263
55. BornemanAR
HynesMJ
AndrianopoulosA
2001 An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei complements the defect in sexual development of an Aspergillus nidulans steA mutant. Genetics 157 1003 1014
56. SugimotoA
IinoY
MaedaT
WatanabeY
YamamotoM
1991 Schizosaccharomyces pombe ste11+ encodes a transcription factor with an HMG motif that is a critical regulator of sexual development. Genes Dev 5 1990 1999
57. HartmannHA
KahmannR
BolkerM
1996 The pheromone response factor coordinates filamentous growth and pathogenicity in Ustilago maydis. EMBO J 15 1632 1641
58. HartmannHA
KrugerJ
LottspeichF
KahmannR
1999 Environmental signals controlling sexual development of the corn smut fungus Ustilago maydis through the transcriptional regulator Prf1. Plant Cell 11 1293 1306
59. HullCM
HeitmanJ
2002 Genetics of Cryptococcus neoformans. Annu Rev Genet 36 557 615
60. TscharkeRL
LazeraM
ChangYC
WickesBL
Kwon-ChungKJ
2003 Haploid fruiting in Cryptococcus neoformans is not mating type alpha-specific. Fungal Genet Biol 39 230 237
61. LengelerKB
FoxDS
FraserJA
AllenA
ForresterK
2002 Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryot Cell 1 704 718
62. KarosM
ChangYC
McClellandCM
ClarkeDL
FuJ
2000 Mapping of the Cryptococcus neoformans MATa locus: presence of mating type-specific mitogen-activated protein kinase cascade homologs. J Bacteriol 182 6222 6227
63. MitchellAP
1998 Dimorphism and virulence in Candida albicans. Curr Opin Microbiol 1 687 692
64. Sanchez-MartinezC
Perez-MartinJ
2001 Dimorphism in fungal pathogens: Candida albicans and Ustilago maydis–similar inputs, different outputs. Curr Opin Microbiol 4 214 221
65. LiuH
2001 Transcriptional control of dimorphism in Candida albicans. Curr Opin Microbiol 4 728 735
66. MullerP
AichingerC
FeldbruggeM
KahmannR
1999 The MAP kinase kpp2 regulates mating and pathogenic development in Ustilago maydis. Mol Microbiol 34 1007 1017
67. Mendoza-MendozaA
EskovaA
WeiseC
CzajkowskiR
KahmannR
2009 Hap2 regulates the pheromone response transcription factor prf1 in Ustilago maydis. Mol Microbiol Epub ahead of print
68. IdnurmA
ReedyJL
NussbaumJC
HeitmanJ
2004 Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryotic Cell 3 420 429
69. IdnurmA
HeitmanJ
2005 Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol 3 e95 doi:10.1371/journal.pbio.0030095
70. WaltonFJ
IdnurmA
HeitmanJ
2005 Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans. Mol Microbiol 57 1381 1396
71. LoftusBJ
FungE
RoncagliaP
RowleyD
AmedeoP
2005 The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 307 1321 1324
72. CasseltonLA
2002 Mate recognition in fungi. Heredity 88 142 147
73. CoppinE
DebuchyR
ArnaiseS
PicardM
1997 Mating types and sexual development in filamentous ascomycetes. Microbiol Mol Biol Rev 61 411 428
74. LinX
HeitmanJ
2007 Mechanisms of homothallism in fungi.
HeitmanJ
KronstadJ
TaylorJ
CasseltonLA
Sex in fungi: molecular determination and evolutionary implications: American Society of Microbiology
75. HeitmanJ
KronstadJ
TaylorJ
CasseltonLA
2007 Sex in fungi : molecular determination and evolutionary implications Washington, D.C. ASM Press xxv 542
76. KrausPR
BoilyMJ
GilesSS
StajichJE
AllenA
2004 Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray. Eukaryot Cell 3 1249 1260
77. XueC
TadaY
DongX
HeitmanJ
2007 The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. Cell Host & Microbe 1 263 273
78. ShenWC
DavidsonRC
CoxGM
HeitmanJ
2002 Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot Cell 1 366 377
79. SiaRA
LengelerKB
HeitmanJ
2000 Diploid strains of the pathogenic basidiomycete Cryptococcus neoformans are thermally dimorphic. Fungal Genet Biol 29 153 163
80. BarchiesiF
CogliatiM
EspostoMC
SpreghiniE
SchimizziAM
2005 Comparative analysis of pathogenicity of Cryptococcus neoformans serotypes A, D and AD in murine cryptococcosis. J Infect 51 10 16
81. LinX
NielsenK
PatelS
HeitmanJ
2008 Impact of mating type, serotype, and ploidy on the virulence of Cryptococcus neoformans. Infect Immun 76 2923 2938
82. LinX
HeitmanJ
2006 The biology of the Cryptococcus neoformans species complex. Annu Rev Microbiol 60 69 105
83. IdnurmA
WaltonFJ
FloydA
HeitmanJ
2008 Identification of the sex genes in an early diverged fungus. Nature 451 193 196
84. LiuH
KohlerJ
FinkGR
1994 Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266 1723 1726
85. KohlerJR
FinkGR
1996 Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development. Proc Natl Acad Sci U S A 93 13223 13228
86. SinghP
GhoshS
DattaA
1997 A novel MAP-kinase kinase from Candida albicans. Gene 190 99 104
87. LebererE
HarcusD
BroadbentID
ClarkKL
DignardD
1996 Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc Natl Acad Sci U S A 93 13217 13222
88. BanuettF
HerskowitzI
1996 Discrete developmental stages during teliospore formation in the corn smut fungus, Ustilago maydis. Development 122 2965 2976
89. WilliamsonJD
SilvermanJF
MallakCT
ChristieJD
1996 Atypical cytomorphologic appearance of Cryptococcus neoformans: a report of five cases. Acta Cytol 40 363 370
90. RipponJW
1988 Medical mycology : the pathogenic fungi and the pathogenic actinomycetes Philadelphia Saunders 797
91. WarrenNG
HazenKC
1999 Candida, Cryptococcus, and other yeasts of medical importance.
MurrayPR
BaronEJ
PfallerMA
Manual of clinical microbiology. 7th ed Washington, D.C. ASM Press 1184 1199
92. BemisDA
KrahwinkelDJ
BowmanLA
MondonP
Kwon-ChungKJ
2000 Temperature-sensitive strain of Cryptococcus neoformans producing hyphal elements in a feline nasal granuloma. J Clin Microbiol 38 926 928
93. FreedER
DumaRJ
ShadomyHJ
UtzJP
1971 Meningoencephalitis due to hyphae-forming Cryptococcus neoformans. Am J Clin Pathol 55 30 33
94. AnandiV
BabuPG
JohnTJ
1991 Infection due to Cryptococcus neoformans of unusual morphology in a patient with AIDS. Mycoses 34 377 379
95. ShadomyHJ
UtzJP
1966 Preliminary studies on a hypha-forming mutant of Cryptococcus neoformans. Mycologia 58 383 390
96. ShadomyHJ
LurieHI
1971 Histopathological observations in experimental cryptococcosis caused by a hypha-producing strain of Cryptococcus neoformans (Coward strain) in mice. Sabouraudia 9 6 9
97. ZimmerBL
HempelHO
GoodmanNL
1983 Pathogenicity of the hyphae of Filobasidiella neoformans. Mycopathologia 81 107 110
98. LurieHI
ShadomyHJ
1971 Morphological variations of a hypha-forming strain of Cryptococcus neoformans (Coward strain) in tissues of mice. Sabouraudia 9 10 14
99. FromtlingRA
BlackstockR
HallNK
BulmerGS
1979 Kinetics of lymphocyte transformation in mice immunized with viable avirulent forms of Cryptococcus neoformans. Infect Immun 24 449 453
100. FromtlingRA
BlackstockR
HallNK
BulmerGS
1979 Immunization of mice with an avirulent pseudohyphal form of Cryptococcus neoformans. Mycopathologia 68 179 181
101. FromtlingRA
BlackstockR
BulmerGS
1980 Immunization and passive transfer in immunity in murine cryptococcosis.
KuttinES
BaumGL
Human and animal mycology : proceedings of the VII Congress of ISHAM Amsterdam; Princeton; New York Excerpta Medica; distributors for the USA, Elsevier North-Holland 122 124
102. HeitmanJ
2009 Microbial genetics: Love the one you're with. Nature 460 807 808
103. PoxleitnerMK
CarpenterML
MancusoJJ
WangCJ
DawsonSC
2008 Evidence for karyogamy and exchange of genetic material in the binucleate intestinal parasite Giardia intestinalis. Science 319 1530 1533
104. CovitzPA
HerskowitzI
MitchellAP
1991 The yeast RME1 gene encodes a putative zinc finger protein that is directly repressed by a1-a2. Genes Dev 5 1982 1989
105. CovitzPA
MitchellAP
1993 Repression by the yeast meiotic inhibitor RME1. Genes Dev 7 1598 1608
106. ShimizuM
LiW
CovitzPA
HaraM
ShindoH
1998 Genomic footprinting of the yeast zinc finger protein Rme1p and its roles in repression of the meiotic activator IME1. Nucleic Acids Res 26 2329 2336
107. MitchellAP
HerskowitzI
1986 Activation of meiosis and sporulation by repression of the RME1 product in yeast. Nature 319 738 742
108. Kwon-ChungKJ
BennettJE
RhodesJC
1982 Taxonomic studies on Filobasidiella species and their anamorphs. Antonie Van Leeuwenhoek 48 25 38
109. LinX
PatelS
LitvintsevaAP
FloydA
MitchellTG
2009 Diploids in the Cryptococcus neoformans serotype A population homozygous for the α mating type originate via unisexual mating. PLoS Pathog 5 e1000283 doi:10.1371/journal.ppat.1000283
110. 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
111. ToffalettiDL
RudeTH
JohnstonSA
DurackDT
PerfectJR
1993 Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol 175 1405 1411
112. ChaskesS
TyndallRL
1978 Pigment production by Cryptococcus neoformans and other Cryptococcus species from aminophenols and diaminobenzenes. J Clin Microbiol 7 146 152
113. CoxGM
MukherjeeJ
ColeGT
CasadevallA
PerfectJR
2000 Urease as a virulence factor in experimental cryptococcosis. Infect Immun 68 443 448
114. HuloN
BairochA
BulliardV
CeruttiL
CucheBA
2008 The 20 years of PROSITE. Nucleic Acids Res 36 D245 249
115. HortonP
ParkKJ
ObayashiT
FujitaN
HaradaH
2007 WoLF PSORT: protein localization predictor. Nucleic Acids Res 35 W585 587
116. Kwon-ChungKJ
KozelTR
EdmanJC
PolacheckI
EllisD
1992 Recent advances in biology and immunology of Cryptococcus neoformans. J Med Vet Mycol 30 Suppl 1 133 142
117. HeitmanJ
AllenB
AlspaughJA
Kwon-ChungKJ
1999 On the origins of congenic MATa and MATa strains of the pathogenic yeast Cryptococcus neoformans. Fungal Genet Biol 28 1 5
118. MooreTD
EdmanJC
1993 The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. Mol Cell Biol 13 1962 1970
119. PerfectJR
LangSD
DurackDT
1980 Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol 101 177 194
120. BahnYS
HicksJK
GilesSS
CoxGM
HeitmanJ
2004 Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade. Eukaryot Cell 3 1476 1491
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2010 Číslo 5
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Common Genetic Variants near the Brittle Cornea Syndrome Locus Influence the Blinding Disease Risk Factor Central Corneal Thickness
- All About Mitochondrial Eve: An Interview with Rebecca Cann
- The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution
- SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling