Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Roles of Zinc-responsive Transcription Factor Csr1 in Filamentous Growth of the Pathogenic Yeast Candida albicans

  • Kim, Min-Jeong (Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University) ;
  • Kil, Min-Kwang (Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University) ;
  • Jung, Jong-Hwan (Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University) ;
  • Kim, Jin-Mi (Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University)
  • Published : 2008.02.29
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Abstract

In the fungal pathogen Candida albicans, the yeast-to-hyphal transition occurs in response to a broad range of environmental stimuli and is considered to be a major virulence factor. To address whether the zinc homeostasis affects the growth or pathogenicity of C. albicans, we functionally characterized the zinc-finger protein Csr1 during filamentation. The deduced amino acid sequence of Csr1 showed a 49% similarity to the zinc-specific transcription factor, Zap1 of Saccharomyces cerevisiae. Sequential disruptions of CSR1 were carried out in diploid C. albicans. The csr1/csr1 mutant strain showed severe growth defects under zinc-limited growth conditions and the filamentation defect under hypha-inducing media. The colony morphology and the germ-tube formation were significantly affected by the csr1 mutation. The expression of the hyphae-specific gene HWP1 was also impaired in csr1/csr1 cells. The C. albicans homologs of ZRTl and ZRT2, which are zinc-transporter genes in S. cerevisiae, were isolated. High-copy number plasmids of these genes suppressed the filamentation defect of the csr1/csr1 mutant strain. We propose that the filamentation phenotype of C. albicans is closely associated with the zinc homeostasis in the cells and that Csr1 plays a critical role in this regulation.

Keywords

References

  1. Adams, A., D. E. Gottschling, C. A. Kaiser, and T. Stearn. 1997. Methods in Yeast Genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
  2. Bedell, G. W. and D. R. Soll. 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
  3. Bird, A. J., H. Zhao, H. Luo, L. T. Jensen, C. Srinivasan, M. Evans-Galea, D. R. Winge, and D. J. Eide. 2000. A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1 transcriptional activator. EMBO J. 19: 3704-3713 https://doi.org/10.1093/emboj/19.14.3704
  4. Calderone, R. A. and W. A. Fonzi. 2001. Virulence factors of Candida albicans. Trends Microbiol. 9: 327-335 https://doi.org/10.1016/S0966-842X(01)02094-7
  5. Campo, A. G. Jr. and C. J. McDonald. 1976. Treatment of acrodermatitis enteropathica with zinc sulfate. Arch. Dermatol. 112: 687-689 https://doi.org/10.1001/archderm.112.5.687
  6. Edman, J., J. D. Sobel, and M. L. Taylor. 1986. Zinc status in women with recurrent vulvovaginal candidiasis. Am. J. Obstet. Gynecol. 155: 1082-1085 https://doi.org/10.1016/0002-9378(86)90355-8
  7. Eide, D. J. 2001. Functional genomics and metal metabolism. Genome Biol. 2: 1028.1-1028.3
  8. Elder, R. T., E. Y. Loh, and R. W. Davis. 1983. RNA from the yeast transposable element Ty1 has both ends in the direct repeats, a structure similar to retrovirus RNA. Proc. Natl. Acad. Sci. USA 80: 2432-2436
  9. Feng, Q., E. Summers, B. Guo, and G. Fink. 1999. Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J. Bacteriol. 181: 6339-6346
  10. Fonzi, W. and M. Irwin. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134: 717-728
  11. Jung, H. J., Y. B. Seu, and D. G. Lee. 2007. Candicidal action of resveratrol isolated from grapes on human pathogenic yeast C. albicans. J. Microbiol. Biotechnol. 17: 1324-1329
  12. Kim, W. I., W. B. Lee, K. Song, and J. Kim. 2000. Identification of a putative DEAD-box RNA helicase and a zinc-finger protein in Candida albicans by functional complementation of the S. cerevisiae rok1 mutation. Yeast 16: 401-409 https://doi.org/10.1002/(SICI)1097-0061(20000330)16:5<401::AID-YEA531>3.0.CO;2-R
  13. Lee, T.-H., M.-D. Kim, and J.-H. Seo. 2006. Development of reusable split URA3-marked knockout vectors for Saccharomyces cerevisiae. J. Microbiol. Biotechnol. 16: 979-982
  14. Lieu, H.-Y., H.-S. Song, S.-N. Yang, J.-H. Kim, H.-J. Kim, Y.-D. Park, C.-S. Park, and H.-Y. Kim. 2006. Identification of proteins affected by iron in Saccharomyces cerevisiae using proteome analysis J. Microbiol. Biotechnol. 16: 946-951
  15. Liu, H. 2001. Transcriptional control of dimorphism in Candida albicans. Curr. Opin. Microbiol. 4: 728-735 https://doi.org/10.1016/S1369-5274(01)00275-2
  16. Liu, H., J. Kohler, and G. R. Fink. 1994. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266: 1723-1726 https://doi.org/10.1126/science.7992058
  17. Lyons, T. J., A. P. Gasch, L. A. Gaither, D. Botstein, P. O. Brown, and D. J. Eide. 2000. Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc. Natl. Acad. Sci. USA 97: 7957-7962
  18. MacDiarmid, C. W., L. A. Gaither, and D. Eide. 2000. Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. EMBO J. 19: 2845-2855 https://doi.org/10.1093/emboj/19.12.2845
  19. Odds, F. C. 1985. Morphogenesis in Candida albicans. Crit. Rev. Microbiol. 12: 45-93 https://doi.org/10.3109/10408418509104425
  20. Pfaller, M. A. 1995. Epidemiology of candidiasis. J. Hosp. Infect. 30: 329-338 https://doi.org/10.1016/0195-6701(95)90036-5
  21. Rutherford, J. C. and A. J. Bird. 2004. Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot. Cell 3: 1-13 https://doi.org/10.1128/EC.3.1.1-13.2004
  22. Sambrook, J. and D. W. Russel. 2001. Molecular Cloning, 3rd Ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
  23. Sikorski, R. S. and P. Hieter. 1989. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122: 19-27
  24. Song, Y., S. Kim, and J. Kim. 1995. ROK1, a high-copy-number plasmid suppressor of kem1, encodes a putative ATP-dependent RNA helicase in Saccharomyces cerevisiae. Gene 166: 151-154 https://doi.org/10.1016/0378-1119(96)80010-2
  25. Stoldt, V. R., A. Sonneborn, C. E. Leuker, and J. F. Ernst. 1997. 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. 16: 1982-1991 https://doi.org/10.1093/emboj/16.8.1982
  26. Sung, W. S., I.-S. Lee, and D. G. Lee. 2007. Damage to the cytoplasmic membrane and cell death caused by lycopene in Candida albicans. J. Microbiol. Biotechnol. 17: 1797-1804
  27. Zhao, H. and D. J. Eide. 1997. Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional regulation in Saccharomyces cerevisiae. Mol. Cell. Biol. 17: 5044-5052 https://doi.org/10.1128/MCB.17.9.5044