請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56350
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林晉玄(Ching-Hsuan Lin) | |
dc.contributor.author | Fu-Sheng Deng | en |
dc.contributor.author | 鄧福勝 | zh_TW |
dc.date.accessioned | 2021-06-16T05:24:37Z | - |
dc.date.available | 2020-08-03 | |
dc.date.copyright | 2020-08-03 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-07-29 | |
dc.identifier.citation | 1. Sullivan, D., The sixth ASM Candida and candidiasis conference. FEMS Yeast Res, 2002. 2(2): p. 249-250. 2. Pappas, P.G., et al., Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis, 2016. 62(4): p. 1-50. 3. Naglik, J.R., S.J. Challacombe, and B. Hube, Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev, 2003. 67(3): p. 400-428, table of contents. 4. Naglik, J.R., P.L. Fidel, Jr., and F.C. Odds, Animal models of mucosal Candida infection. FEMS Microbiol Lett, 2008. 283(2): p. 129-139. 5. Jabra-Rizk, M.A., et al., Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework. Infect Immun, 2016. 84(10): p. 2724-2739. 6. Segura, S.E., G. Ramos-Rivera, and M. Suhrland, Educational Case: Infectious Diseases: Pathogenesis, Diagnosis, Treatment, and Prevention. Acad Pathol, 2018. 5: p. 1-6. 7. Lewis, R.E., et al., Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study. Mycoses, 2013. 56(6): p. 638-645. 8. Parker, J.C., Jr., J.J. McCloskey, and K.A. Knauer, Pathobiologic features of human candidiasis. A common deep mycosis of the brain, heart and kidney in the altered host. Am J Clin Pathol, 1976. 65(6): p. 991-1000. 9. Pfaller, M.A., et al., Multicenter comparison of the VITEK 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing amphotericin B, flucytosine, and voriconazole against Candida spp. J Clin Microbiol, 2007. 45(11): p. 3522-3528. 10. de Oliveira Santos, G.C., et al., Candida Infections and Therapeutic Strategies: Mechanisms of Action for Traditional and Alternative Agents. Front Microbiol, 2018. 9: p. 1351-1323. 11. Ghannoum, M.A. and L.B. Rice, Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev, 1999. 12(4): p. 501-517. 12. Santos, M.A., G. Keith, and M.F. Tuite, Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon. EMBO J, 1993. 12(2): p. 607-616. 13. Nather, K. and C.A. Munro, Generating cell surface diversity in Candida albicans and other fungal pathogens. FEMS Microbiol Lett, 2008. 285(2): p. 137-145. 14. Miranda, I., et al., Candida albicans CUG mistranslation is a mechanism to create cell surface variation. mBio, 2013. 4(4): p. 1-13. 15. Suzuki, T., et al., Variance of ploidy in Candida albicans. J Bacteriol, 1982. 152(2): p. 893-896. 16. Selmecki, A., A. Forche, and J. Berman, Genomic plasticity of the human fungal pathogen Candida albicans. Eukaryot Cell, 2010. 9(7): p. 991-1008. 17. Hickman, M.A., et al., The 'obligate diploid' Candida albicans forms mating-competent haploids. Nature, 2013. 494(7435): p. 55-59. 18. Ford, C.B., et al., The evolution of drug resistance in clinical isolates of Candida albicans. Elife, 2015. 4: p. 1-27. 19. Abbey, D.A., et al., YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens. Genome Med, 2014. 6(100): p. 1-16. 20. Jones, T., et al., The diploid genome sequence of Candida albicans. Proc Natl Acad Sci U S A, 2004. 101(19): p. 7329-7334. 21. Butler, G., et al., Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature, 2009. 459(7247): p. 657-662. 22. Lengauer, C., K.W. Kinzler, and B. Vogelstein, Genetic instability in colorectal cancers. Nature, 1997. 386(6625): p. 623-627. 23. Lengauer, C., K.W. Kinzler, and B. Vogelstein, Genetic instabilities in human cancers. Nature, 1998. 396(6712): p. 643-649. 24. Berman, J., Evolutionary genomics: When abnormality is beneficial. Nature, 2010. 468(7321): p. 183-184. 25. Pavelka, N., et al., Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature, 2010. 468(7321): p. 321-325. 26. Rustchenko, E., Chromosome instability in Candida albicans. FEMS Yeast Res, 2007. 7(1): p. 2-11. 27. Perepnikhatka, V., et al., Specific chromosome alterations in fluconazole-resistant mutants of Candida albicans. J Bacteriol, 1999. 181(13): p. 4041-4049. 28. Selmecki, A., A. Forche, and J. Berman, Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science, 2006. 313(5785): p. 367-370. 29. Hirakawa, M.P., et al., Parasex Generates Phenotypic Diversity de Novo and Impacts Drug Resistance and Virulence in Candida albicans. Genetics, 2017. 207(3): p. 1195-1211. 30. Hull, C.M., R.M. Raisner, and A.D. Johnson, Evidence for mating of the 'asexual' yeast Candida albicans in a mammalian host. Science, 2000. 289(5477): p. 307-310. 31. Lockhart, S.R., et al., In Candida albicans, white-opaque switchers are homozygous for mating type. Genetics, 2002. 162(2): p. 737-745. 32. Miller, M.G. and A.D. Johnson, White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell, 2002. 110(3): p. 293-302. 33. Oyeka, C.A. and L.O. Ugwu, Fungal flora of human toe webs. Mycoses, 2002. 45(11-12): p. 488-491. 34. Hoffmann, C., et al., Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One, 2013. 8(6): p. 1-8. 35. Ghannoum, M.A., et al., Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog, 2010. 6(1): p. 1-8. 36. Findley, K., et al., Topographic diversity of fungal and bacterial communities in human skin. Nature, 2013. 498(7454): p. 367-370. 37. Tao, L., et al., Discovery of a 'white-gray-opaque' tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation. PLoS Biol, 2014. 12(4): p. 1-14. 38. Sudbery, P.E., Growth of Candida albicans hyphae. Nat Rev Microbiol, 2011. 9(10): p. 737-748. 39. Slutsky, B., et al., 'White-opaque transition': a second high-frequency switching system in Candida albicans. J Bacteriol, 1987. 169(1): p. 189-197. 40. Pande, K., C. Chen, and S.M. Noble, Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet, 2013. 45(9): p. 1088-1091. 41. Soll, D.R., High-frequency switching in Candida albicans. Clin Microbiol Rev, 1992. 5(2): p. 183-203. 42. Rikkerink, E.H., B.B. Magee, and P.T. Magee, Opaque-white phenotype transition: a programmed morphological transition in Candida albicans. J Bacteriol, 1988. 170(2): p. 895-899. 43. Huang, G., et al., CO(2) regulates white-to-opaque switching in Candida albicans. Curr Biol, 2009. 19(4): p. 330-334. 44. Huang, G., et al., N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans. PLoS Pathog, 2010. 6(3): p. 1-13. 45. Sun, Y., et al., pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans. Eukaryot Cell, 2015. 14(11): p. 1127-1134. 46. Tuch, B.B., et al., The transcriptomes of two heritable cell types illuminate the circuit governing their differentiation. PLoS Genet, 2010. 6(8): p. 1-16. 47. Anderson, J.M. and D.R. Soll, Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. J Bacteriol, 1987. 169(12): p. 5579-5588. 48. Anderson, J., R. Mihalik, and D.R. Soll, Ultrastructure and antigenicity of the unique cell wall pimple of the Candida opaque phenotype. J Bacteriol, 1990. 172(1): p. 224-235. 49. Sasse, C., et al., White-opaque switching of Candida albicans allows immune evasion in an environment-dependent fashion. Eukaryot Cell, 2013. 12(1): p. 50-58. 50. Kvaal, C., et al., 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, 1999. 67(12): p. 6652-6662. 51. Kvaal, C.A., T. Srikantha, and D.R. Soll, Misexpression of the white-phase-specific gene WH11 in the opaque phase of Candida albicans affects switching and virulence. Infect Immun, 1997. 65(11): p. 4468-4475. 52. Daniels, K.J., et al., Opaque cells signal white cells to form biofilms in Candida albicans. EMBO J, 2006. 25(10): p. 2240-2252. 53. Lachke, S.A., et al., Skin facilitates Candida albicans mating. Infect Immun, 2003. 71(9): p. 4970-4976. 54. Zordan, R.E., et al., Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol, 2007. 5(10): p. 2166-2176. 55. Zordan, R.E., D.J. Galgoczy, and A.D. Johnson, 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, 2006. 103(34): p. 12807-12812. 56. Lassak, T., et al., Target specificity of the Candida albicans Efg1 regulator. Mol Microbiol, 2011. 82(3): p. 602-618. 57. Sriram, K., S. Soliman, and F. Fages, Dynamics of the interlocked positive feedback loops explaining the robust epigenetic switching in Candida albicans. J Theor Biol, 2009. 258(1): p. 71-88. 58. Zhang, A., Z. Liu, and L.C. Myers, Differential regulation of white-opaque switching by individual subunits of Candida albicans mediator. Eukaryot Cell, 2013. 12(9): p. 1293-1304. 59. Hernday, A.D., et al., Structure of the transcriptional network controlling white-opaque switching in Candida albicans. Mol Microbiol, 2013. 90(1): p. 22-35. 60. Liang, S.H., et al., A novel function for Hog1 stress-activated protein kinase in controlling white-opaque switching and mating in Candida albicans. Eukaryot Cell, 2014. 13(12): p. 1557-1566. 61. da Silva Dantas, A., et al., Cell biology of Candida albicans-host interactions. Curr Opin Microbiol, 2016. 34: p. 111-118. 62. Kabir, M.A., M.A. Hussain, and Z. Ahmad, Candida albicans: A Model Organism for Studying Fungal Pathogens. ISRN Microbiol, 2012. 2012: p. 1-15. 63. Hall, R.A., F. Cottier, and F.A. Muhlschlegel, Molecular networks in the fungal pathogen Candida albicans. Adv Appl Microbiol, 2009. 67: p. 191-212. 64. Ghosh, S., et al., Arginine-induced germ tube formation in Candida albicans is essential for escape from murine macrophage line RAW 264.7. Infect Immun, 2009. 77(4): p. 1596-1605. 65. Kong, E. and M.A. Jabra-Rizk, The great escape: pathogen versus host. PLoS Pathog, 2015. 11(3): p. 1-5. 66. Marcil, A., et al., Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of Candida genotype, infection ratios, and gamma interferon treatment. Infect Immun, 2002. 70(11): p. 6319-6329. 67. Moyes, D.L., et al., Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature, 2016. 532(7597): p. 64-68. 68. Kasper, L., et al., The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. Nat Commun, 2018. 9(1): p. 1-20. 69. Gulati, M. and C.J. Nobile, Candida albicans biofilms: development, regulation, and molecular mechanisms. Microbes Infect, 2016. 18(5): p. 310-321. 70. Lowman, D.W., et al., Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast. J Biol Chem, 2014. 289(6): p. 3432-3443. 71. Cheng, S.C., et al., The dectin-1/inflammasome pathway is responsible for the induction of protective T-helper 17 responses that discriminate between yeasts and hyphae of Candida albicans. J Leukoc Biol, 2011. 90(2): p. 357-366. 72. Granger, B.L., et al., Yeast wall protein 1 of Candida albicans. Microbiology, 2005. 151(Pt 5): p. 1631-1644. 73. Phan, Q.T., et al., Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol, 2007. 5(3): p. 0543-0557. 74. Staab, J.F., et al., Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science, 1999. 283(5407): p. 1535-1538. 75. Lo, H.J., et al., Nonfilamentous C. albicans mutants are avirulent. Cell, 1997. 90(5): p. 939-949. 76. Murad, A.M., et al., NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J, 2001. 20(17): p. 4742-4752. 77. Braun, B.R. and A.D. Johnson, Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science, 1997. 277(5322): p. 105-109. 78. Braun, B.R., D. Kadosh, and A.D. Johnson, NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during filament induction. EMBO J, 2001. 20(17): p. 4753-4761. 79. Park, Y.N. and J. Morschhauser, Tetracycline-inducible gene expression and gene deletion in Candida albicans. Eukaryot Cell, 2005. 4(8): p. 1328-1342. 80. Liu, H., J. Kohler, and G.R. Fink, Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science, 1994. 266(5191): p. 1723-1726. 81. Stoldt, V.R., et al., 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, 1997. 16(8): p. 1982-1991. 82. Cao, F., et al., The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell, 2006. 17(1): p. 295-307. 83. Nobile, C.J., et al., A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell, 2012. 148(1-2): p. 126-138. 84. Schweizer, A., et al., The TEA/ATTS transcription factor CaTec1p regulates hyphal development and virulence in Candida albicans. Mol Microbiol, 2000. 38(3): p. 435-445. 85. Lin, C.H., et al., Genetic control of conventional and pheromone-stimulated biofilm formation in Candida albicans. PLoS Pathog, 2013. 9(4): p. 1-14. 86. Scaduto, C.M., et al., Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans. Proc Natl Acad Sci U S A, 2017. 114(52): p. 13780-13785. 87. Caplan, S., et al., Glycosylation and structure of the yeast MF alpha 1 alpha-factor precursor is important for efficient transport through the secretory pathway. J Bacteriol, 1991. 173(2): p. 627-635. 88. Dignard, D., et al., Identification and characterization of MFA1, the gene encoding Candida albicans a-factor pheromone. Eukaryot Cell, 2007. 6(3): p. 487-494. 89. Michaelis, S. and J. Barrowman, Biogenesis of the Saccharomyces cerevisiae pheromone a-factor, from yeast mating to human disease. Microbiol Mol Biol Rev, 2012. 76(3): p. 626-651. 90. Raymond, M., et al., A Ste6p/P-glycoprotein homologue from the asexual yeast Candida albicans transports the a-factor mating pheromone in Saccharomyces cerevisiae. Mol Microbiol, 1998. 27(3): p. 587-598. 91. Bennett, R.J., et al., Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene. Mol Microbiol, 2005. 55(4): p. 1046-1059. 92. Lockhart, S.R., et al., Cell biology of mating in Candida albicans. Eukaryot Cell, 2003. 2(1): p. 49-61. 93. Bennett, R.J. and A.D. Johnson, Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J, 2003. 22(10): p. 2505-2515. 94. Alby, K., et al., Identification of a cell death pathway in Candida albicans during the response to pheromone. Eukaryot Cell, 2010. 9(11): p. 1690-1701. 95. Magee, B.B., et al., Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol Microbiol, 2002. 46(5): p. 1345-1351. 96. Cargnello, M. and P.P. Roux, Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev, 2011. 75(1): p. 50-83. 97. Martin, H., et al., Protein phosphatases in MAPK signalling: we keep learning from yeast. Mol Microbiol, 2005. 58(1): p. 6-16. 98. Cote, P., et al., Evolutionary reshaping of fungal mating pathway scaffold proteins. mBio, 2011. 2(1): p. 1-10. 99. Herrero de Dios, C., et al., The transmembrane protein Opy2 mediates activation of the Cek1 MAP kinase in Candida albicans. Fungal Genet Biol, 2013. 50: p. 21-32. 100. Bhalla, U.S., P.T. Ram, and R. Iyengar, MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network. Science, 2002. 297(5583): p. 1018-1023. 101. Ferguson, B.S., H. Nam, and R.F. Morrison, Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress. Cell Signal, 2019. 53: p. 234-245. 102. Liu, Y., E.G. Shepherd, and L.D. Nelin, MAPK phosphatases--regulating the immune response. Nat Rev Immunol, 2007. 7(3): p. 202-212. 103. Csank, C., et al., Derepressed hyphal growth and reduced virulence in a VH1 family-related protein phosphatase mutant of the human pathogen Candida albicans. Mol Biol Cell, 1997. 8(12): p. 2539-2551. 104. Papa, S. and C. Bubici, Feeding the Hedgehog: A new meaning for JNK signalling in liver regeneration. J Hepatol, 2018. 69(3): p. 572-574. 105. Sun, Y., et al., Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res, 2015. 35(6): p. 600-604. 106. Correia, I., R. Alonso-Monge, and J. Pla, MAPK cell-cycle regulation in Saccharomyces cerevisiae and Candida albicans. Future Microbiol, 2010. 5(7): p. 1125-1141. 107. Monge, R.A., et al., The MAP kinase signal transduction network in Candida albicans. Microbiology, 2006. 152(Pt 4): p. 905-912. 108. Smith, D.A., B.A. Morgan, and J. Quinn, Stress signalling to fungal stress-activated protein kinase pathways. FEMS Microbiol Lett, 2010. 306(1): p. 1-8. 109. Xu, J.R., Map kinases in fungal pathogens. Fungal Genet Biol, 2000. 31(3): p. 137-152. 110. Day, A.M., et al., Stress-induced nuclear accumulation is dispensable for Hog1-dependent gene expression and virulence in a fungal pathogen. Sci Rep, 2017. 7(1): p. 1-11. 111. Leach, M.D., et al., Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast. PLoS Pathog, 2012. 8(12): p. 1-20. 112. Folch-Mallol, J.L., et al., [The stress response in the yeast Saccharomyces cerevisiae]. Rev Latinoam Microbiol, 2004. 46(1-2): p. 24-46. 113. Gustin, M.C., et al., MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev, 1998. 62(4): p. 1264-1300. 114. Tanaka, K., et al., Yeast osmosensors Hkr1 and Msb2 activate the Hog1 MAPK cascade by different mechanisms. Sci Signal, 2014. 7(314): p. 1-10. 115. Arana, D.M., et al., The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology, 2005. 151(Pt 4): p. 1033-1049. 116. Cheetham, J., et al., MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans. J Biol Chem, 2011. 286(49): p. 42002-42016. 117. Cheetham, J., et al., A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans. Mol Biol Cell, 2007. 18(11): p. 4603-4614. 118. Chang, W.H., et al., The conserved dual phosphorylation sites of the Candida albicans Hog1 protein are crucial for white-opaque switching, mating, and pheromone-stimulated cell adhesion. Med Mycol, 2016. 54(6): p. 628-640. 119. Ramirez-Zavala, B., et al., Activation of the Cph1-dependent MAP kinase signaling pathway induces white-opaque switching in Candida albicans. PLoS Pathog, 2013. 9(10): p. 1-17. 120. Eisman, B., et al., The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans. Eukaryot Cell, 2006. 5(2): p. 347-358. 121. Chen, J., et al., A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol Microbiol, 2002. 46(5): p. 1335-1344. 122. Chen, J., Q. Wang, and J.Y. Chen, CEK2, a Novel MAPK from Candida albicans Complement the Mating Defect of fus3/kss1 Mutant. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2000. 32(3): p. 299-304. 123. Guhad, F.A., et al., Reduced pathogenicity of a Candida albicans MAP kinase phosphatase (CPP1) mutant in the murine mastitis model. APMIS, 1998. 106(11): p. 1049-1055. 124. Guhad, F.A., et al., Mitogen-activated protein kinase-defective Candida albicans is avirulent in a novel model of localized murine candidiasis. FEMS Microbiol Lett, 1998. 166(1): p. 135-139. 125. Roman, E., et al., The Cek1 MAPK is a short-lived protein regulated by quorum sensing in the fungal pathogen Candida albicans. FEMS Yeast Res, 2009. 9(6): p. 942-955. 126. Roman, E., C. Nombela, and J. Pla, The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans. Mol Cell Biol, 2005. 25(23): p. 10611-10627. 127. Gonzalez-Rubio, G., et al., Mitogen-Activated Protein Kinase Phosphatases (MKPs) in Fungal Signaling: Conservation, Function, and Regulation. Int J Mol Sci, 2019. 20(7): p. 1-16. 128. Askari, N., et al., p38alpha is active in vitro and in vivo when monophosphorylated at threonine 180. Biochemistry, 2009. 48(11): p. 2497-2504. 129. Nagiec, M.J., et al., Signal inhibition by a dynamically regulated pool of monophosphorylated MAPK. Mol Biol Cell, 2015. 26(18): p. 3359-3371. 130. Vazquez, B., et al., Distinct biological activity of threonine monophosphorylated MAPK isoforms during the stress response in fission yeast. Cell Signal, 2015. 27(12): p. 2534-2542. 131. Dickinson, R.J. and S.M. Keyse, Diverse physiological functions for dual-specificity MAP kinase phosphatases. J Cell Sci, 2006. 119(Pt 22): p. 4607-4615. 132. Franklin, C.C. and A.S. Kraft, Conditional expression of the mitogen-activated protein kinase (MAPK) phosphatase MKP-1 preferentially inhibits p38 MAPK and stress-activated protein kinase in U937 cells. J Biol Chem, 1997. 272(27): p. 16917-16923. 133. Franklin, C.C., S. Srikanth, and A.S. Kraft, Conditional expression of mitogen-activated protein kinase phosphatase-1, MKP-1, is cytoprotective against UV-induced apoptosis. Proc Natl Acad Sci U S A, 1998. 95(6): p. 3014-3019. 134. Sun, H., et al., MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell, 1993. 75(3): p. 487-493. 135. Roth Flach, R.J. and A.M. Bennett, Mitogen-activated protein kinase phosphatase-1 - a potential therapeutic target in metabolic disease. Expert Opin Ther Targets, 2010. 14(12): p. 1323-1332. 136. Tanoue, T., et al., A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol, 2000. 2(2): p. 110-116. 137. Hutter, D., et al., Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation. Biochem J, 2000. 352(Pt 1): p. 155-163. 138. Owens, D.M. and S.M. Keyse, Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene, 2007. 26(22): p. 3203-3213. 139. Brondello, J.M., J. Pouyssegur, and F.R. McKenzie, Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. Science, 1999. 286(5449): p. 2514-2517. 140. Lin, Y.W. and J.L. Yang, Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling. J Biol Chem, 2006. 281(2): p. 915-926. 141. Flandez, M., et al., Reciprocal regulation between Slt2 MAPK and isoforms of Msg5 dual-specificity protein phosphatase modulates the yeast cell integrity pathway. J Biol Chem, 2004. 279(12): p. 11027-11034. 142. Marin, M.J., et al., Different modulation of the outputs of yeast MAPK-mediated pathways by distinct stimuli and isoforms of the dual-specificity phosphatase Msg5. Mol Genet Genomics, 2009. 281(3): p. 345-359. 143. Reuss, O., et al., The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene, 2004. 341: p. 119-127. 144. Bennett, R.J. and A.D. Johnson, The role of nutrient regulation and the Gpa2 protein in the mating pheromone response of C. albicans. Mol Microbiol, 2006. 62(1): p. 100-119. 145. Alby, K., D. Schaefer, and R.J. Bennett, Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature, 2009. 460(7257): p. 890-893. 146. Chen, Y.Z., et al., Zebrafish Egg Infection Model for Studying Candida albicans Adhesion Factors. PLoS One, 2015. 10(11): p. 1-11. 147. Si, H., et al., Candida albicans white and opaque cells undergo distinct programs of filamentous growth. PLoS Pathog, 2013. 9(3): p. 1-19. 148. Bennett, R.J., et al., Identification and characterization of a Candida albicans mating pheromone. Mol Cell Biol, 2003. 23(22): p. 8189-8201. 149. Rastghalam, G., et al., MAP Kinase Regulation of the Candida albicans Pheromone Pathway. mSphere, 2019. 4(1): p. 1-18. 150. Richard, M.L. and A. Plaine, Comprehensive analysis of glycosylphosphatidylinositol-anchored proteins in Candida albicans. Eukaryot Cell, 2007. 6(2): p. 119-133. 151. de Groot, P.W., et al., Adhesins in human fungal pathogens: glue with plenty of stick. Eukaryot Cell, 2013. 12(4): p. 470-481. 152. Emanuelsson, O., et al., Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc, 2007. 2(4): p. 953-971. 153. Pierleoni, A., P.L. Martelli, and R. Casadio, PredGPI: a GPI-anchor predictor. BMC Bioinformatics, 2008. 9(392): p. 1-11. 154. Crooks, G.E., et al., WebLogo: a sequence logo generator. Genome Res, 2004. 14(6): p. 1188-1190. 155. Boisrame, A., et al., Unexpected role for a serine/threonine-rich domain in the Candida albicans Iff protein family. Eukaryot Cell, 2011. 10(10): p. 1317-1330. 156. Nobile, C.J., et al., Function of Candida albicans adhesin Hwp1 in biofilm formation. Eukaryot Cell, 2006. 5(10): p. 1604-1610. 157. Sundstrom, P., Adhesion in Candida spp. Cell Microbiol, 2002. 4(8): p. 461-469. 158. Nantel, A., et al., Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol Biol Cell, 2002. 13(10): p. 3452-3465. 159. Su, C., Y. Lu, and H. Liu, Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity. Mol Biol Cell, 2013. 24(3): p. 385-397. 160. Enjalbert, B., et al., Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans. Mol Biol Cell, 2006. 17(2): p. 1018-1032. 161. Buffo, J., M.A. Herman, and D.R. Soll, A characterization of pH-regulated dimorphism in Candida albicans. Mycopathologia, 1984. 85(1-2): p. 21-30. 162. Mardon, D., E. Balish, and A.W. Phillips, Control of dimorphism in a biochemical variant of Candida albicans. J Bacteriol, 1969. 100(2): p. 701-707. 163. Taschdjian, C.L., J.J. Burchall, and P.J. Kozinn, Rapid identification of Candida albicans by filamentation on serum and serum substitutes. AMA J Dis Child, 1960. 99: p. 212-215. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56350 | - |
dc.description.abstract | MAPK路徑為真核細胞中廣泛存在且具重要性的訊息傳遞路徑,透過磷酸化方式導入外部訊息,並藉以活化特定反應或基因。在本篇研究中,我們證實白色念珠菌磷酸水解酶Cpp1可作為MAP激酶Hog1與Cek1之間連接橋樑,以調控菌體在不同環境刺激下的型態變化以及細胞反應。根據qPCR結果,CPP1基因在hog1∆突變株中的表現量相較於野生株有顯著下降的情形;Western blotting結果亦顯示Cek1激酶蛋白的磷酸化在hog1∆以及cpp1∆突變株中皆有明顯地提升,說明Cpp1作為Cek1磷酸化的抑制子可受Hog1調控基因表現並藉以控制Cek1蛋白磷酸活性。透過進一步的型態測試發現,CPP1基因的剔除可顯著提升菌體white-to-opaque轉換比率、誘導菌絲生成、以及異常地改變費洛蒙誘導的反應型態,而這些的現象亦會隨著CEK1基因的剔除而消失。目前已知Cek1激酶活化為白色念珠菌活化費洛蒙吸附反應的必要因子,本篇研究亦有興趣尋找Cek1下游受轉錄因子Cph1所調節費洛蒙吸附反應的關鍵基因。透過基因轉錄的比較分析,我們系統性地篩選出至少四個受費洛蒙誘導表現的未知基因。利用對突變株的型態測試,我們發現ORF19.1539、ORF19.1725、ORF19.2430以及ORF19.5557,其基因缺失大幅降低白色念珠菌費洛蒙誘導的吸附力,但對於交配反應與交配效率並無造成明顯影響。說明white型態的白色念珠菌在費洛蒙誘導下,可利用Cek1活化下游特定的white-specific基因以啟動菌體吸附反應。此外,qPCR分析亦發現,ORF19.1725基因表現同時受轉錄因子Cph1與Tec1所調控,且其基因缺失對於菌體的生物膜、菌絲生成以及致病力皆有嚴重的影響。這些結果顯示此基因對於白色念珠菌的致病相關機制十分重要。綜合本篇研究的結果,我們對於白色念珠菌MAPK間訊息調控以及下游牽涉的重要基因功能皆有突破性的了解,期許這些成果未來可進一步發展作為臨床上抗真菌藥物開發的重要契機。 | zh_TW |
dc.description.abstract | MAPK (Mitogen-activated protein kinase) cascades are prevalent in nature and are important signaling transduction pathways in Candida albicans. They can be stimulated by external signals through phosphorylation and subsequently activate many response genes. In this study, we demonstrated that a dual-specificity phosphatase Cpp1 serves as a bridge between MAP kinases Cek1 and Hog1. Quantitative PCR revealed that expression of the CPP1 gene was significantly reduced around 30% in hog1∆. In addition, western blotting showed an obvious elevation of Cek1p phosphorylation levels in cpp1∆ and hog1∆ mutants. Further investigation demonstrated that cpp1∆ and hog1∆ showed similar morphology in Lee’s GlcNAc medium on plates, in which both mutant strains exhibited 100% white-to-opaque switching and hyphae formation. These phenotypes disappeared after deletion of the CEK1 gene. The results indicate that Cpp1 is an inhibitor of Cek1p and its gene expression is regulated by Hog1p. We further found that deletion of the CPP1 gene in C. albicans also resulted in abnormal phenotypes during pheromone treatment. Given that Cek1 activity is essential for C. albicans pheromone responses, we found that cpp1∆, compared to the wild-type, exhibited an abnormal elevation in the length of mating projections and the numbers of adherent cells. Through comparative transcriptomic analysis, we identified four target genes that were significantly upregulated in C. albicans white cells during pheromone treatment. Subsequently, we validated Orf19.1539, Orf19.1725, Orf19.2430, and Orf19.5557 as novel factors affecting pheromone-stimulated adhesion in white cells but not mating efficiency in opaque cells, indicating that these genes contribute to the phase- and pheromone-specific responses in C. albicans white cells. Furthermore, ORF19.1725, which encodes an adhesin-like protein, is co-regulated by both transcription factors Cph1 and Tec1. Similar to tec1∆, ORF19.1725 gene deletion significantly inhibited hyphae development, biofilm formation, cell adhesion and pathogenicity in C. albicans. Taken together, we established a model to explain how C. albicans accurately mediates Cek1 activation to regulate its morphogenesis and pheromone responses. Furthermore, our research provides a potential target for new anti-Candida drug development in the future, given the important role of ORF19.1725 in virulence-associated function. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:24:37Z (GMT). No. of bitstreams: 1 U0001-2707202014003100.pdf: 1733532 bytes, checksum: 34d8a08587ccabf48cacd08a9802dd93 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 1. Introduction 8 1.1 Candida albicans 9 1.1.1 General background information of Candida albicans 9 1.1.2 Taxonomy and genetic characteristics of Candida albicans 10 1.1.3 Morphology of Candida albicans 13 1.1.3.1 White-opaque switching 14 1.1.3.2 Yeast-hyphae transition 17 1.1.4 Pheromone responses of Candida albicans 21 1.2 Mitogen-activated protein kinase (MAPK) pathways 24 1.2.1 The activation and inactivation of MAPK pathway 24 1.2.2 Overview of C. albicans MAPK Cek1/Cek2 and Hog1 pathway 27 1.2.3 MAPK phosphatases (MKPs) 30 1.2.3.1 The classification of MAPK phosphatases 31 1.2.3.2 The structure of MAPK phosphatases 32 1.2.3.3 Dual-specificity phosphatase Cpp1 34 1.3 Thesis statement 34 2. Materials and methods 37 2.1 Media and reagents 37 2.2 Plasmids and mutant strains construction 38 2.3 Opaque formation test 43 2.4 Hyphae formation assay 44 2.5 Conventional biofilm assay 44 2.6 Pheromone-induced adhesion assay 45 2.7 Microscopy 45 2.8 Mating efficiency assay 46 2.9 Protein extraction and Western blots 47 2.10 RNA extraction 48 2.11 Quantitative RT-PCR analysis 48 2.12 Growth curve assay 49 2.13 Adhesion assays using zebrafish egg 50 2.14 Virulence of C. albicans using zebrafish embryo infection model 51 2.15 Statistical analysis 51 3. Results 53 3.1 Cek1 activation plays a critical role on hog1∆ opaque formation on SC medium 53 3.2 Cpp1, the critical inhibitor for Cek1 phosphorylation activity, shown down-regulated expression in hog1∆ 54 3.3 Deletion of CPP1 gene induces homologous strains MTLa/a and MTLα/α switching to opaque status on Lee’s GlcNAc condition, but not SC medium 55 3.4 CEK1 gene disruption inhibited white-to-opaque switching in cpp1∆ on Lee’s GlcNAc medium 56 3.5 Cpp1 is involved in yeast-hyphae transition in both white and opaque states 57 3.6 Lack of CPP1 gene enhances the adherent number in C. albicans 59 3.7 Screening for white-specific and Cph1-regulated genes in pheromone-challenged P37005 60 3.8 orf19.1539∆, orf19.1725∆, orf19.2430∆ and orf19.5557∆ reduced cell adhesion ability in white cells during pheromone response but were dispensable in cellular mating of opaque cells in P37005 61 3.9 ORF19.1725 is required for conventional biofilm development 63 3.10 With serum induction, ORF19.1725 deletion caused a severe defect in hyphal formation in C. albicans P37005 64 3.11 ORF19.1725 gene potentially encodes an adhesion protein 65 3.12 Orf19.1725 is required for cell adhesion in zebrafish egg infection model 66 3.13 ORF19.1725 gene deletion significantly reduced fungal virulence in P37005 68 4. Discussion 70 4.1 Cek2 function is not essential for hog1∆ opaque formation on SC medium 70 4.2 Hog1p may control its phosphorylation activity by regulating phosphatase expression of Ptp2 and Ptp3 71 4.3 CPH1 deletion cannot reduce opaque formation and hyphae development in cpp1∆ or hog1∆ 72 4.4 Cpp1 protein maintains a regular molecular weight between wild-type and hog1∆ in different conditions 73 4.5 hog1∆ may affect Ras1/cAMP pathway to induce white-to-opaque switching on Lee’s GlcNAc medium 74 4.6 orf19.1725∆ showed hyphae formation in the zebrafish embryo infection model, but not in serum-containing medium 75 4.7 The novel protein Orf19.1725 fails to be localized by GFP fusion 76 4.8 C. tropicalis and C. dubliniensis contain ORF19.1725 orthologous genes 77 5. List of figures 80 Figure 1 Role of MAP kinase Cek1 in hog1∆-induced opaque switching in SC condition. 80 Figure 2 Identification of potential phosphatases that as signaling cross-linker between Hog1 and Cek1 MAPKs. 81 Figure 3 White-to-opaque switching in homozygous MTLa/a strains of C. albicans on Lee’s GlcNAc plate 82 Figure 4 White and opaque colonies of C. albicans strains on Lee’s GlcNAc and Spider plates. 83 Figure 5 Role of CPP1 gene in formation of pheromone-induced biofilm. 84 Figure 6 Role of the five white-specific and Cph1-dependent genes in pheromone-induced biofilm formation. 85 Figure 7 Mating efficiencies of the C. albicans P37005 and its four white-pecific gene mutants. 86 Figure 8 Role of ORF19.1539 and ORF19.1725 in conventional biofilm formation. 87 Figure 9 Role of ORF19.1725 in C. albicans hyphal formation. 88 Figure 10 The C. albicans Orf19.1725 protein potentially functions as an adhesin. 89 Figure 11 Cell adhesion ability of C. albicans strains in the zebrafish egg bath infection model. 90 Figure 12 Virulence of C. albicans strains in the zebrafish egg bath infection model. 92 Figure 13 Proposed model of signaling responses in C. albicans under certain environmental conditions. 94 6. List of supplementary figures 95 Figure S1 Role of MAP kinase Cek2 in hog1∆-induced opaque switching in SC condition. 95 Figure S2 White-to-opaque switching by cpp1∆, ptp2∆, and ptp3∆ mutants generated in the homozygous C. albicans RBY717 on SC and Lee’s GlcNAc plates. 96 Figure S3 Role of transcription factor Cph1 in opaque formation in hog1∆ or cpp1∆ on SC or Lee’s GlcNAc plates. 97 Figure S4 Analysis of Cpp1 protein level and molecular weight in SDS-PAGE. 98 Figure S5 Role of MAP kinase Cek1 in hog1∆-induced opaque switching on Lee’s GlcNAc plate. 99 Figure S6 Comparison of pheromone-induced adhesion in white C. albicans strains. 100 Figure S7 Examination of 21 downstream targets of Cph1 reveals a general role for Orf19.1725 in biofilm formation. 101 7. References 102 8. Supplementary information 115 Table 1. Strains used in this study 115 Table 2. Oligonucleotides used in this study 122 Table 3. Quantitative PCR primers in this study 129 Appendices 1. A set of protein phosphatases mentioned in this study that be suspected for Cek1p dephosphorylation 130 2. List of transcripts most highly up-regulated by pheromone induction. 131 3. Construction of target gene mutant in C. albicans 133 | |
dc.language.iso | en | |
dc.title | 剖析MAP kinase Cek1調控網絡對於白色念珠球菌型態變化、費洛蒙反應以及致病力的作用 | zh_TW |
dc.title | Dissecting the roles of MAP kinase Cek1 regulatory network in phenotypic transitions, pheromone responses and pathogenicity in Candida albicans | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 羅秀容(Hsiu-Jung Lo),呂俊毅(Jun-Yi Leu),薛雁冰(Yen-Ping Hsueh),楊啟伸(Chii-Shen Yang) | |
dc.subject.keyword | 白色念珠菌,MAPK路徑,Cek1激酶,Hog1激酶,Cpp1磷酸水解酶,費洛蒙反應, | zh_TW |
dc.subject.keyword | C. albicans,MAP kinase,Cek1,Hog1,Cpp1,pheromone responses, | en |
dc.relation.page | 134 | |
dc.identifier.doi | 10.6342/NTU202001903 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-07-29 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
U0001-2707202014003100.pdf 目前未授權公開取用 | 1.69 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。