Mycobiology

The Korean Society of Mycology (한국균학회)
권호 표지
DOI QR코드

DOI QR Code

A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

  • Lee, Kyung-Tae (Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University) ;
  • Kwon, Hyojeong (Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University) ;
  • Lee, Dohyun (Nutrex Technology Co., Ltd.) ;
  • Bahn, Yong-Sun (Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2014.02.15
  • Accepted : 2014.02.20
  • Published : 2014.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

Keywords

References

  1. McLennan AG. The Nudix hydrolase superfamily. Cell Mol Life Sci 2006;63:123-43. https://doi.org/10.1007/s00018-005-5386-7
  2. Xu W, Dunn CA, Bessman MJ. Cloning and characterization of the NADH pyrophosphatases from Caenorhabditis elegans and Saccharomyces cerevisiae, members of a Nudix hydrolase subfamily. Biochem Biophys Res Commun 2000;273:753-8. https://doi.org/10.1006/bbrc.2000.2999
  3. AbdelRaheim SR, Cartwright JL, Gasmi L, McLennan AG. The NADH diphosphatase encoded by the Saccharomyces cerevisiae NPY1 Nudix hydrolase gene is located in peroxisomes. Arch Biochem Biophys 2001;388:18-24. https://doi.org/10.1006/abbi.2000.2268
  4. Cartwright JL, Gasmi L, Spiller DG, McLennan AG. The Saccharomyces cerevisiae PCD1 gene encodes a peroxisomal Nudix hydrolase active toward coenzyme A and its derivatives. J Biol Chem 2000;275:32925-30. https://doi.org/10.1074/jbc.M005015200
  5. Safrany ST, Ingram SW, Cartwright JL, Falck JR, McLennan AG, Barnes LD, Shears SB. The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein. J Biol Chem 1999;274: 21735-40. https://doi.org/10.1074/jbc.274.31.21735
  6. Cartwright JL, McLennan AG. The Saccharomyces cerevisiae YOR163w gene encodes a diadenosine 5', 5"'-P1,P6- hexaphosphate (Ap6A) hydrolase member of the MutT motif (Nudix hydrolase) family. J Biol Chem 1999;274:8604-10. https://doi.org/10.1074/jbc.274.13.8604
  7. Dunckley T, Parker R. The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif. EMBO J 1999;18:5411-22. https://doi.org/10.1093/emboj/18.19.5411
  8. Dunn CA, O'Handley SF, Frick DN, Bessman MJ. Studies on the ADP-ribose pyrophosphatase subfamily of the Nudix hydrolases and tentative identification of trgB, a gene associated with tellurite resistance. J Biol Chem 1999;274:32318-24. https://doi.org/10.1074/jbc.274.45.32318
  9. Tong L, Lee S, Denu JM. Hydrolase regulates NAD+ metabolites and modulates cellular redox. J Biol Chem 2009;284:11256-66. https://doi.org/10.1074/jbc.M809790200
  10. Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem Sci 2007;32:12-9. https://doi.org/10.1016/j.tibs.2006.11.006
  11. Kim H, Jacobson EL, Jacobson MK. Synthesis and degradation of cyclic ADP-ribose by NAD glycohydrolases. Science 1993; 261:1330-3. https://doi.org/10.1126/science.8395705
  12. Bang S, Lee D, Kim H, Park J, Bahn YS. Global transcriptome analysis of eukaryotic genes affected by gromwell extract. J Sci Food Agric 2014;94:445-52. https://doi.org/10.1002/jsfa.6265
  13. Perfect JR, Ketabchi N, Cox GM, Ingram CW, Beiser CL. Karyotyping of Cryptococcus neoformans as an epidemiological tool. J Clin Microbiol 1993;31:3305-9.
  14. Kim MS, Kim SY, Yoon JK, Lee YW, Bahn YS. An efficient gene-disruption method in Cryptococcus neoformans by double-joint PCR with NAT-split markers. Biochem Biophys Res Commun 2009;390:983-8. https://doi.org/10.1016/j.bbrc.2009.10.089
  15. Davidson RC, Cruz MC, Sia RA, Allen B, Alspaugh JA, Heitman J. Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans. Fungal Genet Biol 2000;29:38-48. https://doi.org/10.1006/fgbi.1999.1180
  16. Liang Q, Zhou B. Copper and manganese induce yeast apoptosis via different pathways. Mol Biol Cell 2007;18:4741-9. https://doi.org/10.1091/mbc.E07-05-0431
  17. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161-208. https://doi.org/10.2174/0929867053764635
  18. Berger NA. Poly(ADP-ribose) in the cellular response to DNA damage. Radiat Res 1985;101:4-15. https://doi.org/10.2307/3576299
  19. Schreiber V, Dantzer F, Ame JC, de Murcia G. Poly(ADPribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 2006;7:517-28. https://doi.org/10.1038/nrm1963
  20. Ferreira GF, Baltazar Lde M, Santos JR, Monteiro AS, Fraga LA, Resende-Stoianoff MA, Santos DA. The role of oxidative and nitrosative bursts caused by azoles and amphotericin B against the fungal pathogen Cryptococcus gattii. J Antimicrob Chemother 2013;68:1801-11. https://doi.org/10.1093/jac/dkt114
  21. Lamy-Freund MT, Ferreira VF, Schreier S. Mechanism of inactivation of the polyene antibiotic amphotericin B. Evidence for radical formation in the process of autooxidation. J Antibiot (Tokyo) 1985;38:753-7. https://doi.org/10.7164/antibiotics.38.753
  22. Giaever G, Chu AM, Ni L, Connelly C, Riles L, Véronneau S, Dow S, Lucau-Danila A, Anderson K, André B, et al. Functional profiling of the Saccharomyces cerevisiae genome. Nature 2002;418:387-91. https://doi.org/10.1038/nature00935
  23. Svensson JP, Pesudo LQ, Fry RC, Adeleye YA, Carmichael P, Samson LD. Genomic phenotyping of the essential and nonessential yeast genome detects novel pathways for alkylation resistance. BMC Syst Biol 2011;5:157. https://doi.org/10.1186/1752-0509-5-157
  24. Shimizu M, Masuo S, Fujita T, Doi Y, Kamimura Y, Takaya N. Hydrolase controls cellular NAD, sirtuin, and secondary metabolites. Mol Cell Biol 2012;32:3743-55. https://doi.org/10.1128/MCB.00032-12
  25. Barkauskaite E, Jankevicius G, Ladurner AG, Ahel I, Timinszky G. The recognition and removal of cellular poly(ADP-ribose) signals. FEBS J 2013;280:3491-507. https://doi.org/10.1111/febs.12358
  26. Koh DW, Lawler AM, Poitras MF, Sasaki M, Wattler S, Nehls MC, Stöger T, Poirier GG, Dawson VL, Dawson TM. Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proc Natl Acad Sci U S A 2004;101:17699-704. https://doi.org/10.1073/pnas.0406182101
  27. Tong L, Denu JM. Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose. Biochim Biophys Acta 2010; 1804:1617-25. https://doi.org/10.1016/j.bbapap.2010.02.007
  28. Kruszewski M, Szumiel I. Sirtuins (histone deacetylases III) in the cellular response to DNA damage: facts and hypotheses. DNA Repair (Amst) 2005;4:1306-13. https://doi.org/10.1016/j.dnarep.2005.06.013
  29. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 2003; 423:181-5. https://doi.org/10.1038/nature01578
  30. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 2002;277:45099-107. https://doi.org/10.1074/jbc.M205670200
  31. Semighini CP, Savoldi M, Goldman GH, Harris SD. Functional characterization of the putative Aspergillus nidulans poly(ADPribose) polymerase homolog PrpA. Genetics 2006;173:87-98. https://doi.org/10.1534/genetics.105.053199
  32. Kothe GO, Kitamura M, Masutani M, Selker EU, Inoue H. PARP is involved in replicative aging in Neurospora crassa. Fungal Genet Biol 2010;47:297-309. https://doi.org/10.1016/j.fgb.2009.12.012