–Independent Phenotypic Switching in and a Dual Role for Wor1 in Regulating Switching and Filamentation

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Phenotypic switching allows for rapid transitions between alternative cell states and is important in pathogenic fungi for colonization and infection of different host niches. In Candida albicans, the white-opaque phenotypic switch plays a central role in regulating the program of sexual mating as well as interactions with the mammalian host. White-opaque switching is controlled by genes encoded at the MTL (mating-type-like) locus that ensures that only a or α cells can switch from the white state to the mating-competent opaque state, while a/α cells are refractory to switching. Here, we show that the related pathogen C. tropicalis undergoes white-opaque switching in all three cell types (a, α, and a/α), and thus switching is independent of MTL control. We also demonstrate that C. tropicalis white cells are themselves mating-competent, albeit at a lower efficiency than opaque cells. Transcriptional profiling of C. tropicalis white and opaque cells reveals significant overlap between switch-regulated genes in MTL homozygous and MTL heterozygous cells, although twice as many genes are white-opaque regulated in a/α cells as in a cells. In C. albicans, the transcription factor Wor1 is the master regulator of the white-opaque switch, and we show that Wor1 also regulates switching in C. tropicalis; deletion of WOR1 locks a, α, and a/α cells in the white state, while WOR1 overexpression induces these cells to adopt the opaque state. Furthermore, we show that WOR1 overexpression promotes both filamentous growth and biofilm formation in C. tropicalis, independent of the white-opaque switch. These results demonstrate an expanded role for C. tropicalis Wor1, including the regulation of processes necessary for infection of the mammalian host. We discuss these findings in light of the ancestral role of Wor1 as a transcriptional regulator of the transition between yeast form and filamentous growth.

Vyšlo v časopise: –Independent Phenotypic Switching in and a Dual Role for Wor1 in Regulating Switching and Filamentation. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003369
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003369

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Zdroje

1. BrownGD, DenningDW, LevitzSM (2012) Tackling human fungal infections. Science 336: 647.

2. PfallerMA, DiekemaDJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20: 133–163.

3. HedgesSB, BlairJE, VenturiML, ShoeJL (2004) A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol Biol 4: 2.

4. PesoleG, LottiM, AlberghinaL, SacconeC (1995) Evolutionary origin of nonuniversal CUGSer codon in some Candida species as inferred from a molecular phylogeny. Genetics 141: 903–907.

5. PormanAM, AlbyK, HirakawaMP, BennettRJ (2011) Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis. Proc Natl Acad Sci U S A 108: 21158–21163.

6. SlutskyB, StaebellM, AndersonJ, RisenL, PfallerM, et al. (1987) “White-opaque transition”: a second high-frequency switching system in Candida albicans. J Bacteriol 169: 189–197.

7. PujolC, DanielsKJ, LockhartSR, SrikanthaT, RadkeJB, et al. (2004) The closely related species Candida albicans and Candida dubliniensis can mate. Eukaryot Cell 3: 1015–1027.

8. XieJ, DuH, GuanG, TongY, KourkoumpetisTK, et al. (2012) N-acetylglucosamine induces white-to-opaque switching and mating in Candida tropicalis, providing new insights into adaptation and fungal sexual evolution. Eukaryot Cell 11: 773–782.

9. LanCY, NewportG, MurilloLA, JonesT, SchererS, et al. (2002) Metabolic specialization associated with phenotypic switching in Candida albicans. Proc Natl Acad Sci U S A 99: 14907–14912.

10. AlbyK, BennettRJ (2009) Stress-induced phenotypic switching in Candida albicans. Mol Biol Cell 20: 3178–3191.

11. HuangG, SrikanthaT, SahniN, YiS, SollDR (2009) CO(2) regulates white-to-opaque switching in Candida albicans. Curr Biol 19: 330–334.

12. HuangG, YiS, SahniN, DanielsKJ, SrikanthaT, et al. (2010) N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans. PLoS Pathog 6: e1000806 doi:10.1371/journal.ppat.1000806.

13. KolotilaMP, DiamondRD (1990) Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1. Infect Immun 58: 1174–1179.

14. Ramirez-ZavalaB, ReussO, ParkYN, OhlsenK, MorschhauserJ (2008) Environmental induction of white-opaque switching in Candida albicans. PLoS Pathog 4: e1000089 doi:10.1371/journal.ppat.1000089.

15. GeigerJ, WesselsD, LockhartSR, SollDR (2004) Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by white-opaque switching in Candida albicans. Infect Immun 72: 667–677.

16. LohseMB, JohnsonAD (2008) Differential phagocytosis of white versus opaque Candida albicans by Drosophila and mouse phagocytes. PLoS ONE 3: e1473 doi:10.1371/journal.pone.0001473.

17. LockhartSR, PujolC, DanielsKJ, MillerMG, JohnsonAD, et al. (2002) In Candida albicans, white-opaque switchers are homozygous for mating type. Genetics 162: 737–745.

18. MillerMG, JohnsonAD (2002) White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110: 293–302.

19. StokesC, MoranGP, SpieringMJ, ColeGT, ColemanDC, et al. (2007) Lower filamentation rates of Candida dubliniensis contribute to its lower virulence in comparison with Candida albicans. Fungal Genet Biol 44: 920–931.

20. ButlerG, RasmussenMD, LinMF, SantosMA, SakthikumarS, et al. (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459: 657–662.

21. TsongAE, MillerMG, RaisnerRM, JohnsonAD (2003) Evolution of a combinatorial transcriptional circuit: a case study in yeasts. Cell 115: 389–399.

22. TuchBB, MitrovichQM, HomannOR, HerndayAD, MonighettiCK, et al. (2010) The transcriptomes of two heritable cell types illuminate the circuit governing their differentiation. PLoS Genet 6: e1001070 doi:10.1371/journal.pgen.1001070.

23. AndersonJ, CundiffL, SchnarsB, GaoMX, MackenzieI, et al. (1989) Hypha formation in the white-opaque transition of Candida albicans. Infect Immun 57: 458–467.

24. ErnstJF (2000) Transcription factors in Candida albicans - environmental control of morphogenesis. Microbiology 146 (Pt 8) 1763–1774.

25. HuangG, WangH, ChouS, NieX, ChenJ, et al. (2006) Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci U S A 103: 12813–12818.

26. SrikanthaT, BornemanAR, DanielsKJ, PujolC, WuW, et al. (2006) TOS9 regulates white-opaque switching in Candida albicans. Eukaryot Cell 5: 1674–1687.

27. ZordanRE, GalgoczyDJ, JohnsonAD (2006) Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop. Proc Natl Acad Sci U S A 103: 12807–12812.

28. AlbyK, SchaeferD, BennettRJ (2009) Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460: 890–893.

29. ZordanRE, MillerMG, GalgoczyDJ, TuchBB, JohnsonAD (2007) Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans. PLoS Biol 5: e256 doi:10.1371/journal.pbio.0050256.

30. LohseMB, ZordanRE, CainCW, JohnsonAD (2010) Distinct class of DNA-binding domains is exemplified by a master regulator of phenotypic switching in Candida albicans. Proc Natl Acad Sci U S A 107: 14105–14110.

31. CainCW, LohseMB, HomannOR, SilA, JohnsonAD (2012) A conserved transcriptional regulator governs fungal morphology in widely diverged species. Genetics 190: 511–521.

32. NguyenVQ, SilA (2008) Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator. Proc Natl Acad Sci U S A 105: 4880–4885.

33. AndersonJM, SollDR (1987) Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. J Bacteriol 169: 5579–5588.

34. LiuH, KohlerJ, FinkGR (1994) Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266: 1723–1726.

35. FinkelJS, MitchellAP (2011) Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9: 109–118.

36. NobileCJ, MitchellAP (2006) Genetics and genomics of Candida albicans biofilm formation. Cell Microbiol 8: 1382–1391.

37. McCreathKJ, SpechtCA, RobbinsPW (1995) Molecular cloning and characterization of chitinase genes from Candida albicans. Proc Natl Acad Sci U S A 92: 2544–2548.

38. NettJE, LepakAJ, MarchilloK, AndesDR (2009) Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis 200: 307–313.

39. LegrandM, LephartP, ForcheA, MuellerFM, WalshT, et al. (2004) Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic rearrangements and tetraploid formation. Mol Microbiol 52: 1451–1462.

40. FromtlingRA, AbruzzoGK, GiltinanDM (1987) Candida tropicalis infection in normal, diabetic, and neutropenic mice. J Clin Microbiol 25: 1416–1420.

41. DignardD, AndreD, WhitewayM (2008) Heterotrimeric G-protein subunit function in Candida albicans: both the alpha and beta subunits of the pheromone response G protein are required for mating. Eukaryot Cell 7: 1591–1599.

42. JonesSKJr, BennettRJ (2011) Fungal mating pheromones: choreographing the dating game. Fungal Genet Biol 48: 668–676.

43. LengelerKB, DavidsonRC, D'SouzaC, HarashimaT, ShenWC, et al. (2000) Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64: 746–785.

44. AlbyK, BennettRJ (2010) Sexual reproduction in the Candida clade: cryptic cycles, diverse mechanisms, and alternative functions. Cell Mol Life Sci

45. LohseMB, JohnsonAD (2009) White-opaque switching in Candida albicans. Curr Opin Microbiol 12: 650–654.

46. MorschhauserJ (2010) Regulation of white-opaque switching in Candida albicans. Med Microbiol Immunol 199: 165–172.

47. SollDR (2009) Why does Candida albicans switch? FEMS Yeast Res 9: 973–989.

48. KvaalC, LachkeSA, SrikanthaT, DanielsK, McCoyJ, et al. (1999) Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infect Immun 67: 6652–6662.

49. KvaalCA, SrikanthaT, SollDR (1997) Misexpression of the white-phase-specific gene WH11 in the opaque phase of Candida albicans affects switching and virulence. Infect Immun 65: 4468–4475.

50. LaffeySF, ButlerG (2005) Phenotype switching affects biofilm formation by Candida parapsilosis. Microbiology 151: 1073–1081.

51. TuchBB, GalgoczyDJ, HerndayAD, LiH, JohnsonAD (2008) The evolution of combinatorial gene regulation in fungi. PLoS Biol 6: e38 doi:10.1371/journal.pbio.0060038.

52. Guthrie C, Fink GR (1991) Guide to Yeast Genetics and Molecular Biology. San Diego: Academic Press.

53. ReussO, VikA, KolterR, MorschhauserJ (2004) The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341: 119–127.

54. BedellGW, SollDR (1979) Effects of low concentrations of zinc on the growth and dimorphism of Candida albicans: evidence for zinc-resistant and -sensitive pathways for mycelium formation. Infect Immun 26: 348–354.

55. ParkYN, MorschhauserJ (2005) Tetracycline-inducible gene expression and gene deletion in Candida albicans. Eukaryot Cell 4: 1328–1342.