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The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen


Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species. The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microconidia. Light induces the differentiation of conidia and apothecia, while sclerotia are exclusively formed in the absence of light. The relevance of light for virulence of the fungus is not obvious, but infections are observed under natural illumination as well as in constant darkness. By a random mutagenesis approach, we identified a novel virulence-related gene encoding a GATA transcription factor (BcLTF1 for light-responsive TF1) with characterized homologues in Aspergillus nidulans (NsdD) and Neurospora crassa (SUB-1). By deletion and over-expression of bcltf1, we confirmed the predicted role of the transcription factor in virulence, and discovered furthermore its functions in regulation of light-dependent differentiation, the equilibrium between production and scavenging of reactive oxygen species (ROS), and secondary metabolism. Microarray analyses revealed 293 light-responsive genes, and that the expression levels of the majority of these genes (66%) are modulated by BcLTF1. In addition, the deletion of bcltf1 affects the expression of 1,539 genes irrespective of the light conditions, including the overexpression of known and so far uncharacterized secondary metabolism-related genes. Increased expression of genes encoding alternative respiration enzymes, such as the alternative oxidase (AOX), suggest a mitochondrial dysfunction in the absence of bcltf1. The hypersensitivity of Δbctlf1 mutants to exogenously applied oxidative stress - even in the absence of light - and the restoration of virulence and growth rates in continuous light by antioxidants, indicate that BcLTF1 is required to cope with oxidative stress that is caused either by exposure to light or arising during host infection.


Vyšlo v časopise: The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004040
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004040

Souhrn

Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species. The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microconidia. Light induces the differentiation of conidia and apothecia, while sclerotia are exclusively formed in the absence of light. The relevance of light for virulence of the fungus is not obvious, but infections are observed under natural illumination as well as in constant darkness. By a random mutagenesis approach, we identified a novel virulence-related gene encoding a GATA transcription factor (BcLTF1 for light-responsive TF1) with characterized homologues in Aspergillus nidulans (NsdD) and Neurospora crassa (SUB-1). By deletion and over-expression of bcltf1, we confirmed the predicted role of the transcription factor in virulence, and discovered furthermore its functions in regulation of light-dependent differentiation, the equilibrium between production and scavenging of reactive oxygen species (ROS), and secondary metabolism. Microarray analyses revealed 293 light-responsive genes, and that the expression levels of the majority of these genes (66%) are modulated by BcLTF1. In addition, the deletion of bcltf1 affects the expression of 1,539 genes irrespective of the light conditions, including the overexpression of known and so far uncharacterized secondary metabolism-related genes. Increased expression of genes encoding alternative respiration enzymes, such as the alternative oxidase (AOX), suggest a mitochondrial dysfunction in the absence of bcltf1. The hypersensitivity of Δbctlf1 mutants to exogenously applied oxidative stress - even in the absence of light - and the restoration of virulence and growth rates in continuous light by antioxidants, indicate that BcLTF1 is required to cope with oxidative stress that is caused either by exposure to light or arising during host infection.


Zdroje

1. WilliamsonB, TudzynskiB, TudzynskiP, van KanJA (2007) Botrytis cinerea: the cause of grey mould disease. Mol Plant Pathol 8: 561–580.

2. AmselemJ, CuomoCA, van KanJA, ViaudM, BenitoEP, et al. (2011) Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea. PLoS Genet 7: e1002230.

3. Van KanJA (2006) Licensed to kill: the lifestyle of a necrotrophic plant pathogen. Trends Plant Sci 11: 247–253.

4. Sharon A, Elad Y, Barakat R, Tudzynski P (2004) Phytohormones in Botrytis-plant interactions. In: Elad Y, Williamson B, Tudzynski P, Delen N, editors. Botrytis: biology, pathology, control. Kluwer, Dordrecht. pp. 163–179.

5. ChoquerM, FournierE, KunzC, LevisC, PradierJM, et al. (2007) Botrytis cinerea virulence factors: new insights into a necrotrophic and polyphageous pathogen. FEMS Microbiol Lett 277: 1–10.

6. Tudzynski P, Kokkelink L (2009) Botrytis cinerea: Molecular aspects of a necrotrophic life style. In: Deising H, editor. The Mycota V, Plant Relationships, 2nd Edition. Springer-Verlag Berlin Heidelberg. pp. 29–50.

7. SiewersV, ViaudM, Jimenez-TejaD, ColladoIG, Schulze GronoverC, et al. (2005) Functional analysis of the cytochrome P450 monooxygenase gene bcbot1 of Botrytis cinerea indicates that botrydial is a strain-specific virulence factor. Mol Plant-Microbe Interact 18: 602–612.

8. PinedoC, WangCM, PradierJM, DalmaisB, ChoquerM, et al. (2008) Sesquiterpene synthase from the botrydial biosynthetic gene cluster of the phytopathogen Botrytis cinerea. ACS Chem Biol 3: 791–801.

9. DalmaisB, SchumacherJ, MoragaJ, LePêcheurP, TudzynskiB, et al. (2011) The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases for production and has a redundant role in virulence with botrydial. Mol Plant Pathol 12: 564–579.

10. FaretraF, AntonacciE (1987) Production of apothecia of Botryotinia fuckeliana (de Bary) Whetz under controlled environmental conditions. Phytopathol Mediterr 26: 29–35.

11. GiraudT, FortiniD, LevisC, LerouxP, BrygooY (1997) RFLP markers show genetic recombination in Botryotinia fuckeliana (Botrytis cinerea) and transposable elements reveal two sympatric species. Mol Biol Evol 14: 1177–1185.

12. FaretraF, AntonacciE, PollastroS (1988) Sexual behaviour and mating system of Botryotinia fuckeliana, teleomorph of Botrytis cinerea. J Gen Microbiol 134: 2543–2550.

13. PaulWRC (1929) A comparative morphological and physiological study of a number of strains of Botrytis cinerea Pers. with special reference to their virulence. Trans Br Mycol Soc 14: 118–134.

14. QuiddeT, OsbournAE, TudzynskiP (1998) Detoxification of α-tomatine by Botrytis cinerea. Physiol Mol Plant Pathol 52: 151–165.

15. TanKK, EptonHAS (1973) Effect of light on the growth and sporulation of Botrytis cinerea. Trans Br Mycol Soc 61: 147–157.

16. TanKK (1974) Blue-light inhibition of sporulation in Botrytis cinerea. J Gen Microbiol 82: 191–200.

17. TanKK (1975) Interaction of near-ultraviolet, blue, red, and far-red light in sporulation of Botrytis cinerea. Trans Br Mycol Soc 64: 215–222.

18. Schumacher J, Tudzynski P (2012) Morphogenesis and infection in Botrytis cinerea. In: Pérez-Martín J, Di Pietro A, editors. Topics in Current Genetics, Vol. Morphogenesis and Pathogenicity in Fungi. Springer-Verlag Berlin, Heidelberg. pp. 225–241.

19. LindenH, BallarioP, MacinoG (1997) Blue light regulation in Neurospora crassa. Fungal Genet Biol 22: 141–150.

20. ChenCH, DunlapJC, LorosJJ (2010) Neurospora illuminates fungal photoreception. Fungal Genet Biol 47: 922–929.

21. ShimuraM, ItoY, IshiiC, YajimaH, LindenH, et al. (1999) Characterization of a Neurospora crassa photolyase-deficient mutant generated by repeat induced point mutation of the phr gene. Fungal Genet Biol 28: 12–20.

22. FroehlichAC, ChenCH, BeldenWJ, MadetiC, RoennebergT, et al. (2010) Genetic and molecular characterization of a cryptochrome from the filamentous fungus Neurospora crassa. Eukaryot Cell 9: 738–750.

23. BieszkeJA, BraunEL, BeanLE, KangS, NatvigDO, et al. (1999) The nop-1 gene of Neurospora crassa encodes a seven transmembrane helix retinal-binding protein homologous to archaeal rhodopsins. Proc Natl Acad Sci USA 96: 8034–8039.

24. FroehlichAC, NohB, VierstraRD, LorosJ, DunlapJC (2005) Genetic and molecular analysis of phytochromes from the filamentous fungus Neurospora crassa. Eukaryot Cell 4: 2140–2152.

25. AdamsTH, WieserJK, YuJH (1998) Asexual sporulation in Aspergillus nidulans. Microbiol Mol Biol Rev 62: 35–54.

26. HanKH (2009) Molecular Genetics of Emericella nidulans sexual development. Mycobiol 37: 171–182.

27. BayramO, BiesemannC, KrappmannS, GallandP, BrausGH (2008) More than a repair enzyme: Aspergillus nidulans photolyase-like CryA is a regulator of sexual development. Mol Biol Cell 19: 3254–3262.

28. PurschwitzJ, MüllerS, KastnerC, SchöserM, HaasH, et al. (2008) Functional and physical interaction of blue- and red-light sensors in Aspergillus nidulans. Curr Biol 18: 255–259.

29. Rodriguez-RomeroJ, HedtkeM, KastnerC, MüllerS, FischerR (2010) Fungi, hidden in soil or up in the air: light makes a difference. Annu Rev Microbiol 64: 585–610.

30. HellerJ, RuhnkeN, EspinoJ, MassaroliM, ColladoIG, et al. (2012) The MAP kinase BcSak1 of Botrytis cinerea is required for pathogenic development and has broad regulatory functions beyond stress response. Mol Plant Microbe Interact 25: 802–816.

31. SchumacherJ, PradierJM, SimonA, TraegerS, MoragaJ, et al. (2012) Natural variation in the VELVET gene bcvel1 affects virulence and light-dependent differentiation in Botrytis cinerea. PLoS One 7: e47840.

32. SchumacherJ, GautierA, MorgantG, StudtL, DucrotPH, et al. (2013) A functional bikaverin biosynthesis gene cluster in rare strains of Botrytis cinerea is positively controlled by VELVET. PLoS One 8: e53729.

33. HanKH, HanKY, YuJH, ChaeKS, JahngKY, et al. (2001) The nsdD gene encodes a putative GATA-type transcription factor necessary for sexual development of Aspergillus nidulans. Mol Microbiol 41: 299–309.

34. GrosseV, KrappmannS (2008) The asexual pathogen Aspergillus fumigatus expresses functional determinants of Aspergillus nidulans sexual development. Eukaryot Cell 7: 1724–1732.

35. SzewczykE, KrappmannS (2010) Conserved regulators of mating are essential for Aspergillus fumigatus cleistothecium formation. Eukaryot Cell 9: 774–783.

36. ColotHV, ParkG, TurnerGE, RingelbergC, CrewCM, et al. (2006) A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors. Proc Natl Acad Sci USA 103: 10352–10357.

37. ChenCH, RingelbergCS, GrossRH, DunlapJC, LorosJJ (2009) Genome-wide analysis of light-inducible responses reveals hierarchical light signalling in Neurospora. EMBO J 28: 1029–1042.

38. NowrousianM, TeichertI, MasloffS, KückU (2012) Whole-genome sequencing of Sordaria macrospora mutants identifies developmental genes. G3 (Bethesda) 2: 261–270.

39. GiesbertS, SchumacherJ, KupasV, EspinoJ, SegmüllerN, et al. (2012) Identification of pathogenesis-associated genes by T-DNA-mediated insertional mutagenesis in Botrytis cinerea: A type 2A phosphoprotein phosphatase and a SPT3 transcription factor have significant impact on virulence. Mol Plant Microbe Interact 25: 481–495.

40. LiM, RollinsJA (2009) The development-specific protein (Ssp1) from Sclerotinia sclerotiorum is encoded by a novel gene expressed exclusively in sclerotium tissues. Mycologia 101: 34–43.

41. KrokenS, GlassNL, TaylorJW, YoderOC, TurgeonBG (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Natl Acad Sci USA 100: 15670–15675.

42. LorosJJ, DenomeSA, DunlapJC (1989) Molecular cloning of genes under control of the circadian clock in Neurospora. Science 243: 385–388.

43. LerochM, MernkeD, KoppenhoeferD, SchneiderP, MosbachA, et al. (2011) Living colors in the gray mold pathogen Botrytis cinerea: codon-optimized genes encoding green fluorescent protein and mCherry, which exhibit bright fluorescence. Appl Environ Microbiol 77: 2887–2897.

44. GovrinEM, LevineA (2000) The hypersensitive response facilitates plant infection by the necrotrophic pathogen Botrytis cinerea. Curr Biol 10: 751–757.

45. HellerJ, MeyerAJ, TudzynskiP (2012) Redox-sensitive GFP2: use of the genetically encoded biosensor of the redox status in the filamentous fungus Botrytis cinerea. Mol Plant Pathol 13: 935–947.

46. SubramanianA, KuehnH, GouldJ, TamayoP, MesirovJP (2007) GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics 23: 3251–3253.

47. MoothaVK, LindgrenCM, ErikssonKF, SubramanianA, SihagS, et al. (2003) PGC-1 alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34: 267–273.

48. SmithKM, SancarG, DekhangR, SullivanCM, LiS, et al. (2010) Transcription factors in light and circadian clock signaling networks revealed by genome-wide mapping of direct targets for Neurospora white collar complex. Eukaryot Cell 9: 1549–1556.

49. ChristieJM (2007) Phototropin blue-light receptors. Annu Rev Plant Biol 58: 21–45.

50. SimonA, DalmaisB, MorgantG, ViaudM (2013) Screening of a Botrytis cinerea one-hybrid library reveals a Cys(2)His(2) transcription factor involved in the regulation of secondary metabolism gene clusters. Fungal Genet Biol 52: 9–19.

51. HoffmeisterD, KellerNP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24: 393–416.

52. ThewesS, Prado-CabreroA, PradoMM, TudzynskiB, AvalosJ (2005) Characterization of a gene in the car cluster of Fusarium fujikuroi that codes for a protein of the carotenoid oxygenase family. Mol Genet Genomics 274: 217–228.

53. Prado-CabreroA, ScherzingerD, AvalosJ, Al-BabiliS (2007) Retinal biosynthesis in fungi: characterization of the carotenoid oxygenase CarX from Fusarium fujikuroi. Eukaryot Cell 6: 650–657.

54. AvalosJ, EstradaAF (2010) Regulation by light in Fusarium. Fungal Genet Biol 47: 930–938.

55. HellerJ, TudzynskiP (2011) Reactive oxygen species in phytopathogenic fungi: signaling, development, and disease. Annu Rev Phytopathol 49: 369–390.

56. RhoadsDM, UmbachAL, SubbaiahCC, SiedowJN (2006) Mitochondrial reactive oxygen species. Contribution to oxidative stress and interorganellar signaling. Plant Physiol 141: 357–366.

57. Van AkenO, GiraudE, CliftonR, WhelanJ (2009) Alternative oxidase: a target and regulator of stress responses. Physiol Plant 137: 354–361.

58. VolkovAN, NichollsP, WorrallJA (2011) The complex of cytochrome c and cytochrome c peroxidase: the end of the road? Biochim Biophys Acta 1807: 1482–1503.

59. JarmuszkiewiczW, Woyda-PloszczycaA, Antos-KrzeminskaN, SluseFE (2010) Mitochondrial uncoupling proteins in unicellular eukaryotes. Biochim Biophys Acta 1797: 792–799.

60. SchumacherJ, de LarrinoaIF, TudzynskiB (2008) Calcineurin-responsive zinc finger transcription factor CRZ1 of Botrytis cinerea is required for growth, development, and full virulence on bean plants. Eukaryot Cell 7: 584–601.

61. CaryJW, Harris-CowardPY, EhrlichKC, MackBM, KaleSP, et al. (2012) NsdC and NsdD affect Aspergillus flavus morphogenesis and aflatoxin production. Eukaryot Cell 11: 1104–1111.

62. UrbaschI (1985) Ultrastructural studies on the microconidia of Botrytis cinerea Pers. and their phialoconidial development. Phytopath Z 112: 229–237.

63. Jarvis WR (1977) Botryotinia and Botrytis Species: Taxonomy, Physiology and Pathogenicity. A Guide to the Literature. Canadian Department of Agriculture, Ottawa. pp. 38–39.

64. Ruger-HerrerosC, Rodríguez-RomeroJ, Fernández-BarrancoR, OlmedoM, FischerR, et al. (2011) Regulation of conidiation by light in Aspergillus nidulans. Genetics 188: 809–822.

65. FullerKK, RingelbergCS, LorosJJ, DunlapJC (2013) The fungal pathogen Aspergillus fumigatus regulates growth, metabolism, and stress resistance in response to light. MBio 4: e00142–13.

66. SchumacherJ (2012) Tools for Botrytis cinerea: new expression vectors make the gray mold fungus more accessible to cell biology approaches. Fungal Genet Biol 49: 483–497.

67. HeintzenC, LorosJJ, DunlapJC (2001) The PAS protein VIVID defines a clock-associated feedback loop that represses light input, modulates gating, and regulates clock resetting. Cell 104: 453–464.

68. SchwerdtfegerC, LindenH (2003) VIVID is a flavoprotein and serves as a fungal blue light photoreceptor for photoadaptation. EMBO J 22: 4846–4855.

69. DossRP, DeisenhoferJ, Krug von NiddaHA, SoeldnerAH, McGuireRP (2003) Melanin in the extracellular matrix of germlings of Botrytis cinerea. Phytochemistry 63: 687–691.

70. ZeunR, BuchenauerH (1985) Effect of tricyclazole on production and melanin contents of sclerotia of Botrytis cinerea. Phytopathol Z 112: 259–267.

71. GaoQ, Garcia-PichelF (2011) Microbial ultraviolet sunscreens. Nat Rev Microbiol 9: 791–802.

72. StrobelI, BreitenbachJ, ScheckhuberCQ, OsiewaczHD, SandmannG (2009) Carotenoids and carotenogenic genes in Podospora anserina: engineering of the carotenoid composition extends the life span of the mycelium. Curr Genet 55: 175–184.

73. SchwarzländerM, FrickerMD, MüllerC, MartyL, BrachT, et al. (2008) Confocal imaging of glutathione redox potential in living plant cells. J Microsc 231: 299–316.

74. RhoadsDM, SubbaiahCC (2007) Mitochondrial retrograde regulation in plants. Mitochondrion 7: 177–194.

75. DuarteM, VideiraA (2009) Effects of mitochondrial complex III disruption in the respiratory chain of Neurospora crassa. Mol Microbiol 72: 246–258.

76. SellemCH, MarsyS, BoivinA, LemaireC, Sainsard-ChanetA (2007) A mutation in the gene encoding cytochrome c1 leads to a decreased ROS content and to a long-lived phenotype in the filamentous fungus Podospora anserina. Fungal Genet Biol 44: 648–658.

77. GrahlN, DinamarcoTM, WillgerSD, GoldmanGH, CramerRA (2012) Aspergillus fumigatus mitochondrial electron transport chain mediates oxidative stress homeostasis, hypoxia responses and fungal pathogenesis. Mol Microbiol 84: 383–399.

78. DufourE, BoulayJ, RinchevalV, Sainsard-ChanetA (2000) A causal link between respiration and senescence in Podospora anserina. Proc Natl Acad Sci USA 97: 4138–4143.

79. MagnaniT, SorianiFM, MartinsVP, NascimentoAM, TudellaVG, et al. (2007) Cloning and functional expression of the mitochondrial alternative oxidase of Aspergillus fumigatus and its induction by oxidative stress. FEMS Microbiol Lett 271: 230–238.

80. HondaY, HattoriT, KirimuraK (2012) Visual expression analysis of the responses of the alternative oxidase gene (aox1) to heat shock, oxidative, and osmotic stresses in conidia of citric acid-producing Aspergillus niger. J Biosci Bioeng 113: 338–342.

81. YukiokaH, InagakiS, TanakaR, KatohK, MikiN, et al. (1998) Transcriptional activation of the alternative oxidase gene of the fungus Magnaporthe grisea by a respiratory-inhibiting fungicide and hydrogen peroxide. Biochim Biophys Acta 1442: 161–169.

82. MartinsVP, DinamarcoTM, SorianiFM, TudellaVG, OliveiraSC, et al. (2011) Involvement of an alternative oxidase in oxidative stress and mycelium-to-yeast differentiation in Paracoccidioides brasiliensis. Eukaryot Cell 10: 237–248.

83. BorghoutsC, ScheckhuberCQ, StephanO, OsiewaczHD (2002) Copper homeostasis and aging in the fungal model system Podospora anserina: differential expression of PaCtr3 encoding a copper transporter. Int J Biochem Cell Biol 34: 1355–1371.

84. StumpferlSW, StephanO, OsiewaczHD (2004) Impact of a disruption of a pathway delivering copper to mitochondria on Podospora anserina metabolism and life span. Eukaryot Cell 3: 200–211.

85. Avila-AdameC, KöllerW (2002) Disruption of the alternative oxidase gene in Magnaporthe grisea and its impact on host infection. Mol Plant Microbe Interact 15: 493–500.

86. MagnaniT, SorianiFM, Martins VdeP, PolicarpoAC, SorgiCA, et al. (2008) Silencing of mitochondrial alternative oxidase gene of Aspergillus fumigatus enhances reactive oxygen species production and killing of the fungus by macrophages. J Bioenerg Biomembr 40: 631–636.

87. LorinS, DufourE, BoulayJ, BegelO, MarsyS, et al. (2001) Overexpression of the alternative oxidase restores senescence and fertility in a long-lived respiration-deficient mutant of Podospora anserina. Mol Microbiol 42: 1259–1267.

88. ScheckhuberCQ, HouthoofdK, WeilAC, WernerA, De VreeseA, et al. (2011) Alternative oxidase dependent respiration leads to an increased mitochondrial content in two long-lived mutants of the aging model Podospora anserina. PLoS One 6: e16620.

89. SchwarzländerM, FrickerMD, SweetloveLJ (2009) Monitoring the in vivo redox state of plant mitochondria: effect of respiratory inhibitors, abiotic stress and assessment of recovery from oxidative challenge. Biochim Biophys Acta 1787: 468–475.

90. ButowRA, AvadhaniNG (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14: 1–15.

91. StaatsM, van KanJA (2012) Genome update of Botrytis cinerea strains B05.10 and T4. Eukaryot Cell 11: 1413–1414.

92. PontecorvoGV, RoperJA, HemmonsLM, MacDonaldKD, BuftonAWJ (1953) The genetics of Aspergillus nidulans. Adv Genet 5: 141–238.

93. CenisJL (1992) Rapid extraction of fungal DNA for PCR amplification. Nucleic Acids Res 20: 2380.

94. SiewersV, SmedsgaardJ, TudzynskiP (2004) The P450 monooxygenase BcABA1 is essential for abscisic acid biosynthesis in Botrytis cinerea. Appl Environ Microbiol 70: 3868–3876.

95. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd ed., Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

96. TemmeN, TudzynskiP (2009) Does Botrytis cinerea ignore H(2)O(2)-induced oxidative stress during infection? Characterization of Botrytis activator protein 1. Mol Plant Microbe Interact 22: 987–998.

97. DoehlemannG, BerndtP, HahnM (2006) Different signalling pathways involving a Galpha protein, cAMP and a MAP kinase control germination of Botrytis cinerea conidia. Mol Microbiol 59: 821–835.

98. RocaMG, WeichertM, SiegmundU, TudzynskiP, FleissnerA (2012) Germling fusion via conidial anastomosis tubes in the grey mould Botrytis cinerea requires NADPH oxidase activity. Fungal Biol 116: 379–387.

99. SimonA, BiotE (2010) ANAIS: Analysis of NimbleGen Arrays Interface. Bioinformatics 26: 2468–2469.

100. IrizarryRA, HobbsB, CollinF, Beazer-BarclayYD, AntonellisKJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264.

101. BolstadBM, IrizarryRA, AstrandM, SpeedTP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193.

102. SturnA, QuackenbushJ, TrajanoskiZ (2002) Genesis: cluster analysis of microarray data. Bioinformatics 18: 207–208.

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