#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Hos2 Histone Deacetylase Controls Virulence through Direct Regulation of Mating-Type Genes


Many pathogenic fungi need to undergo morphological changes in order to infect their hosts. Typically, pathogenic fungi switch from a non-pathogenic yeast-like form to a polarised pathogenic filament. This morphological switch is regulated genetically and is triggered by specific environmental conditions. Histone deacetylases (HDACs) are important regulators of chromatin structure and gene expression. In this study, we investigate the role of HDACs as targets of the signalling pathways that activate fungal virulence programs in response to specific external signals. We identify two specific HDACs, Hos2 and Clr3, that are required for the virulence of the corn smut fungus, Ustilago maydis. Our results reveal that Hos2 and Clr3 function in the cAMP-PKA cascade, a nutrient-sensing pathway conserved between all eukaryotes.


Vyšlo v časopise: The Hos2 Histone Deacetylase Controls Virulence through Direct Regulation of Mating-Type Genes. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005134
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005134

Souhrn

Many pathogenic fungi need to undergo morphological changes in order to infect their hosts. Typically, pathogenic fungi switch from a non-pathogenic yeast-like form to a polarised pathogenic filament. This morphological switch is regulated genetically and is triggered by specific environmental conditions. Histone deacetylases (HDACs) are important regulators of chromatin structure and gene expression. In this study, we investigate the role of HDACs as targets of the signalling pathways that activate fungal virulence programs in response to specific external signals. We identify two specific HDACs, Hos2 and Clr3, that are required for the virulence of the corn smut fungus, Ustilago maydis. Our results reveal that Hos2 and Clr3 function in the cAMP-PKA cascade, a nutrient-sensing pathway conserved between all eukaryotes.


Zdroje

1. Schulz B, Banuett F, Dahl M, Schlesinger R, Schafer W, et al. (1990) The b alleles of U. maydis, whose combinations program pathogenic development, code for polypeptides containing a homeodomain-related motif. Cell 60(2): 295–306. 1967554

2. Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, et al. (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90(5): 939–949. 9298905

3. Lin X, Huang JC, Mitchell TG, Heitman J. (2006) Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation. PLoS Genet 2(11): e187. doi: 10.1371/journal.pgen.0020187 17112316

4. Nadal M, Garcia-Pedrajas MD, Gold SE. (2008) Dimorphism in fungal plant pathogens. FEMS Microbiol Lett 284(2): 127–134. doi: 10.1111/j.1574–6968.2008.01173.x 18479435

5. Braun BR, Johnson AD. (2000) TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans. Genetics 155(1): 57–67. 10790384

6. Sanchez-Martinez C, Perez-Martin J. (2001) Dimorphism in fungal pathogens: Candida albicans and ustilago maydis—similar inputs, different outputs. Curr Opin Microbiol 4(2): 214–221. 11282479

7. Liu H. (2002) Co-regulation of pathogenesis with dimorphism and phenotypic switching in candida albicans, a commensal and a pathogen. Int J Med Microbiol 292(5–6): 299–311. 12452278

8. Brefort T, Doehlemann G, Mendoza-Mendoza A, Reissmann S, Djamei A, et al. (2009) Ustilago maydis as a pathogen. Annu Rev Phytopathol 47: 423–445. doi: 10.1146/annurev-phyto-080508–081923 19400641

9. Bolker M. (2001) Ustilago maydis—a valuable model system for the study of fungal dimorphism and virulence. Microbiology 147(Pt 6): 1395–1401. 11390671

10. Snetselaar KM, Mims CW. (1992) Sporidial fusion and infection of maize seedlings by the smut fungus ustilago maydis. Mycologia 84(2): 193–203.

11. Snetselaar KM, Mims CW. (1994) Light and electron microscopy of ustilago maydis hyphae in maize. Mycol Res 98(3): 347–355.

12. Mendoza-Mendoza A, Berndt P, Djamei A, Weise C, Linne U, et al. (2009) Physical-chemical plant-derived signals induce differentiation in ustilago maydis. Mol Microbiol 71(4): 895–911. doi: 10.1111/j.1365–2958.2008.06567.x 19170880

13. Banuett F, Herskowitz I. (1996) Discrete developmental stages during teliospore formation in the corn smut fungus, ustilago maydis. Development 122(10): 2965–2976. 8898211

14. Bolker M, Urban M, Kahmann R. (1992) The a mating type locus of U. maydis specifies cell signaling components. Cell 68(3): 441–450. 1310895

15. Spellig T, Bolker M, Lottspeich F, Frank RW, Kahmann R. (1994) Pheromones trigger filamentous growth in ustilago maydis. EMBO J 13(7): 1620–1627. 8157001

16. Gillissen B, Bergemann J, Sandmann C, Schroeer B, Bolker M, et al. (1992) A two-component regulatory system for self/non-self recognition in ustilago maydis. Cell 68(4): 647–657. 1739973

17. Kamper J, Reichmann M, Romeis T, Bolker M, Kahmann R. (1995) Multiallelic recognition: Nonself-dependent dimerization of the bE and bW homeodomain proteins in ustilago maydis. Cell 81(1): 73–83. 7720075

18. Hartmann HA, Kahmann R, Bolker M. (1996) The pheromone response factor coordinates filamentous growth and pathogenicity in ustilago maydis. EMBO J 15(7): 1632–1641. 8612587

19. 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(7): 1293–1306. 10402430

20. Muller P, Aichinger C, Feldbrugge M, Kahmann R. (1999) The MAP kinase kpp2 regulates mating and pathogenic development in ustilago maydis. Mol Microbiol 34(5): 1007–1017. 10594825

21. 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(21): 5817–5826. doi: 10.1093/emboj/cdg554 14592979

22. Muller P, Weinzierl G, Brachmann A, Feldbrugge M, Kahmann R. (2003) Mating and pathogenic development of the smut fungus ustilago maydis are regulated by one mitogen-activated protein kinase cascade. Eukaryot Cell 2(6): 1187–1199. 14665454

23. Kruger J, Loubradou G, Regenfelder E, Hartmann A, Kahmann R. (1998) Crosstalk between cAMP and pheromone signalling pathways in ustilago maydis. Mol Gen Genet 260(2–3): 193–198. 9862471

24. Brefort T, Muller P, Kahmann R. (2005) The high-mobility-group domain transcription factor Rop1 is a direct regulator of prf1 in ustilago maydis. Eukaryot Cell 4(2): 379–391. doi: 10.1128/EC.4.2.379–391.2005 15701800

25. Mendoza-Mendoza A, Eskova A, Weise C, Czajkowski R, Kahmann R. (2009) Hap2 regulates the pheromone response transcription factor prf1 in ustilago maydis. Mol Microbiol 72(3): 683–698. doi: 10.1111/j.1365–2958.2009.06676.x 19400774

26. Garrido E, Voss U, Muller P, Castillo-Lluva S, Kahmann R, et al. (2004) The induction of sexual development and virulence in the smut fungus ustilago maydis depends on Crk1, a novel MAPK protein. Genes Dev 18(24): 3117–3130. doi: 10.1101/gad.314904 15601825

27. Elias-Villalobos A, Fernandez-Alvarez A, Ibeas JI. (2011) The general transcriptional repressor Tup1 is required for dimorphism and virulence in a fungal plant pathogen. PLoS Pathog 7(9): e1002235. doi: 10.1371/journal.ppat.1002235 21909277

28. Pijnappel WW, Schaft D, Roguev A, Shevchenko A, Tekotte H, et al. (2001) The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program. Genes Dev 15(22): 2991–3004. doi: 10.1101/gad.207401 11711434

29. Wang A, Kurdistani SK, Grunstein M. (2002) Requirement of Hos2 histone deacetylase for gene activity in yeast. Science 298(5597): 1412–1414. doi: 10.1126/science.1077790 12434058

30. Hang M, Smith MM. (2011) Genetic analysis implicates the Set3/Hos2 histone deacetylase in the deposition and remodeling of nucleosomes containing H2A.Z. Genetics 187(4): 1053–1066. doi: 10.1534/genetics.110.125419 21288874

31. Kim T, Buratowski S. (2009) Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions. Cell 137(2): 259–272. doi: 10.1016/j.cell.2009.02.045 19379692

32. Hnisz D, Majer O, Frohner IE, Komnenovic V, Kuchler K. (2010) The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of candida albicans. PLoS Pathog 6(5): e1000889. doi: 10.1371/journal.ppat.1000889 20485517

33. Ding SL, Liu W, Iliuk A, Ribot C, Vallet J, et al. (2010) The tig1 histone deacetylase complex regulates infectious growth in the rice blast fungus magnaporthe oryzae. Plant Cell 22(7): 2495–2508. doi: 10.1105/tpc.110.074302 20675574

34. Baidyaroy D, Brosch G, Ahn JH, Graessle S, Wegener S, et al. (2001) A gene related to yeast HOS2 histone deacetylase affects extracellular depolymerase expression and virulence in a plant pathogenic fungus. Plant Cell 13(7): 1609–1624. 11449054

35. Reichmann M, Jamnischek A, Weinzierl G, Ladendorf O, Huber S, et al. (2002) The histone deacetylase Hda1 from ustilago maydis is essential for teliospore development. Mol Microbiol 46(4): 1169–1182. 12421320

36. Gonzalez-Prieto JM, Dominguez A, Rosas-Quijano R, Cervantes-Chavez JA, Ruiz-Herrera J. (2004) Isolation and molecular analysis of Umhda2 a gene encoding a histone deacetylase from ustilago maydis. DNA Seq 15(1): 44–50. 15354354

37. Wirén M, Silverstein RA, Sinha I, Walfridsson J, Lee H, et al. (2005) Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast. The EMBO Journal 24(16): 2906–2918. doi: 10.1038/sj.emboj.7600758 16079916

38. Olsson TG, Ekwall K, Allshire RC, Sunnerhagen P, Partridge JF, et al. (1998) Genetic characterisation of hda1+, a putative fission yeast histone deacetylase gene. Nucleic Acids Res 26(13): 3247–3254. 9628926

39. Kim YB, Honda A, Yoshida M, Horinouchi S. (1998) Phd1+, a histone deacetylase gene of schizosaccharomyces pombe, is required for the meiotic cell cycle and resistance to trichostatin A. FEBS Letters 436(2): 193. 9781677

40. Bolker M, Genin S, Lehmler C, Kahmann R. (1995) Genetic regulation of mating, and dimorphism in ustilago maydis. Can J Bot 73: 320–325.

41. Brachmann A, Weinzierl G, Kamper J, Kahmann R. (2001) Identification of genes in the bW/bE regulatory cascade in ustilago maydis. Mol Microbiol 42(4): 1047–1063. 11737646

42. Flor-Parra I, Vranes M, Kamper J, Perez-Martin J. (2006) Biz1, a zinc finger protein required for plant invasion by ustilago maydis, regulates the levels of a mitotic cyclin. Plant Cell 18(9): 2369–2387. doi: 10.1105/tpc.106.042754 16905655

43. 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(8): e1001035. doi: 10.1371/journal.ppat.1001035 20700446

44. Watson AD, Edmondson DG, Bone JR, Mukai Y, Yu Y, et al. (2000) Ssn6-Tup1 interacts with class I histone deacetylases required for repression. Genes Dev 14(21): 2737–2744. 11069890

45. Davie JK, Edmondson DG, Coco CB, Dent SY. (2003) Tup1-Ssn6 interacts with multiple class I histone deacetylases in vivo. J Biol Chem 278(50): 50158–50162. doi: 10.1074/jbc.M309753200 14525981

46. Barrett KJ, Gold SE, Kronstad JW. (1993) Identification and complementation of a mutation to constitutive filamentous growth in ustilago maydis. Mol Plant Microbe Interact 6(3): 274–283. 8324246

47. Gold S, Duncan G, Barrett K, Kronstad J. (1994) cAMP regulates morphogenesis in the fungal pathogen ustilago maydis. Genes Dev 8(23): 2805–2816. 7995519

48. Durrenberger F, Wong K, Kronstad JW. (1998) Identification of a cAMP-dependent protein kinase catalytic subunit required for virulence and morphogenesis in ustilago maydis. Proc Natl Acad Sci U S A 95(10): 5684–5689. 9576944

49. Mayorga ME, Gold SE. (1998) Characterization and molecular genetic complementation of mutants affecting dimorphism in the fungus ustilago maydis. Fungal Genet Biol 24(3): 364–376. doi: 10.1006/fgbi.1998.1078 9756717

50. Hnisz D, Bardet AF, Nobile CJ, Petryshyn A, Glaser W, et al. (2012) A histone deacetylase adjusts transcription kinetics at coding sequences during candida albicans morphogenesis. PLoS Genetics 8(12): e1003118. doi: 10.1371/journal.pgen.1003118 23236295

51. Robbins N, Leach MD, Cowen LE. (2012) Lysine deacetylases Hda1 and Rpd3 regulate Hsp90 function thereby governing fungal drug resistance. Cell Rep 2(4): 878–888. doi: 10.1016/j.celrep.2012.08.035 23041319

52. Haberland M, Carrer M, Mokalled MH, Montgomery RL, Olson EN. (2010) Redundant control of adipogenesis by histone deacetylases 1 and 2. J Biol Chem 285(19): 14663–14670. doi: 10.1074/jbc.M109.081679 20190228

53. Barrales RR, Korber P, Jimenez J, Ibeas JI. (2012) Chromatin modulation at the FLO11 promoter of saccharomyces cerevisiae by HDAC and swi/snf complexes. Genetics 191(3): 791–803. doi: 10.1534/genetics.112.140301 22542969

54. Zacchi LF, Schulz WL, Davis DA. (2010) HOS2 and HDA1 encode histone deacetylases with opposing roles in candida albicans morphogenesis. PLoS One 5(8): e12171. doi: 10.1371/journal.pone.0012171 20730094

55. Izawa M, Takekawa O, Arie T, Teraoka T, Yoshida M, et al. (2009) Inhibition of histone deacetylase causes reduction of appressorium formation in the rice blast fungus magnaporthe oryzae. J Gen Appl Microbiol 55(6): 489–498. 20118613

56. Li Y, Wang C, Liu W, Wang G, Kang Z, et al. (2011) The HDF1 histone deacetylase gene is important for conidiation, sexual reproduction, and pathogenesis in fusarium graminearum. Mol Plant Microbe Interact 24(4): 487–496. doi: 10.1094/MPMI-10–10–0233 21138346

57. Wong KH, Struhl K. (2011) The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein. Genes Dev 25(23): 2525–2539. doi: 10.1101/gad.179275.111 22156212

58. Parnell EJ, Stillman DJ. (2011) Shields up: The Tup1-Cyc8 repressor complex blocks coactivator recruitment. Genes Dev 25(23): 2429–2435. doi: 10.1101/gad.181768.111 22156205

59. Martinez-Salgado JL, Leon-Ramirez CG, Pacheco AB, Ruiz-Herrera J, de la Rosa A P. (2013) Analysis of the regulation of the ustilago maydis proteome by dimorphism, pH or MAPK and GCN5 genes. J Proteomics 79: 251–262. doi: 10.1016/j.jprot.2012.12.022 23305952

60. González-Prieto JM, Rosas-Quijano R, Domínguez A, Ruiz-Herrera J. (2014) The UmGcn5 gene encoding histone acetyltransferase from ustilago maydis is involved in dimorphism and virulence. Fungal Genetics and Biology: FG & B 71: 86–95. doi: 10.1016/j.fgb.2014.09.002

61. Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, et al. (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109(4): 437–446. 12086601

62. van Werven FJ, Neuert G, Hendrick N, Lardenois A, Buratowski S, et al. (2012) Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding yeast. Cell 150(6): 1170–1181. doi: 10.1016/j.cell.2012.06.049 22959267

63. Lu Y, Su C, Wang A, Liu H. (2011) Hyphal development in candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance. PLoS Biol 9(7): e1001105. doi: 10.1371/journal.pbio.1001105 21811397

64. Sambrook J, Frish E, Maniatis T. (1989) Molecular cloning: A laboratorymanual. New York: Cold Spring Harbour Laboratory Press.

65. Holliday R. (1974) Ustilago maydis. New York, USA: Plenum Press: Handbook of Genetics. 575 p.

66. Kamper J. (2004) A PCR-based system for highly efficient generation of gene replacement mutants in ustilago maydis. Mol Genet Genomics 271(1): 103–110. doi: 10.1007/s00438–003–0962–8 14673645

67. Brachmann A, Konig J, Julius C, Feldbrugge M. (2004) A reverse genetic approach for generating gene replacement mutants in ustilago maydis. Mol Genet Genomics 272(2): 216–226. doi: 10.1007/s00438–004–1047-z 15316769

68. Wedlich-Soldner R, Bolker M, Kahmann R, Steinberg G. (2000) A putative endosomal t-SNARE links exo- and endocytosis in the phytopathogenic fungus ustilago maydis. EMBO J 19(9): 1974–1986. doi: 10.1093/emboj/19.9.1974 10790364

69. Scherer M, Heimel K, Starke V, Kamper J. (2006) The Clp1 protein is required for clamp formation and pathogenic development of ustilago maydis. Plant Cell 18(9): 2388–2401. doi: 10.1105/tpc.106.043521 16920779

70. Zarnack K, Eichhorn H, Kahmann R, Feldbrugge M. (2008) Pheromone-regulated target genes respond differentially to MAPK phosphorylation of transcription factor Prf1. Mol Microbiol 69(4): 1041–1053. doi: 10.1111/j.1365–2958.2008.06345.x 18627457

71. Heimel K, Scherer M, Schuler D, Kamper J. (2010) The ustilago maydis Clp1 protein orchestrates pheromone and b-dependent signaling pathways to coordinate the cell cycle and pathogenic development. Plant Cell 22(8): 2908–2922. doi: 10.1105/tpc.110.076265 20729384

72. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, et al. (2011) MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28(10): 2731–2739. doi: 10.1093/molbev/msr121 21546353

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#