DOI QR코드

DOI QR Code

The Zinc Transport Systems and Their Regulation in Pathogenic Fungi

  • Jung, Won Hee (Department of Systems Biotechnology, Chung-Ang University)
  • Received : 2015.08.07
  • Accepted : 2015.08.18
  • Published : 2015.09.30

Abstract

Zinc is an essential micronutrient required for many enzymes that play essential roles in a cell. It was estimated that approximately 3% of the total cellular proteins are required for zinc for their functions. Zinc has long been considered as one of the key players in host-pathogen interactions. The host sequesters intracellular zinc by utilizing multiple cellular zinc importers and exporters as a means of nutritional immunity. To overcome extreme zinc limitation within the host environment, pathogenic microbes have successfully evolved a number of mechanisms to secure sufficient concentrations of zinc for their survival and pathogenesis. In this review, we briefly discuss the zinc uptake systems and their regulation in the model fungus Saccharomyces cerevisiae and in major human pathogenic fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus gattii.

Keywords

References

  1. Eide DJ. The molecular biology of metal ion transport in Saccharomyces cerevisiae. Annu Rev Nutr 1998;18:441-69. https://doi.org/10.1146/annurev.nutr.18.1.441
  2. Eide DJ. Multiple regulatory mechanisms maintain zinc homeostasis in Saccharomyces cerevisiae. J Nutr 2003;133(5 Suppl 1):1532S-5S. https://doi.org/10.1093/jn/133.5.1532S
  3. Andreini C, Bertini I. A bioinformatics view of zinc enzymes. J Inorg Biochem 2012;111:150-6. https://doi.org/10.1016/j.jinorgbio.2011.11.020
  4. Costello LC, Liu Y, Franklin RB, Kennedy MC. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem 1997;272:28875-81. https://doi.org/10.1074/jbc.272.46.28875
  5. Zackular JP, Chazin WJ, Skaar EP. Nutritional immunity: S100 proteins at the host-pathogen interface. J Biol Chem 2015;290:18991-8. https://doi.org/10.1074/jbc.R115.645085
  6. Cerasi M, Ammendola S, Battistoni A. Competition for zinc binding in the host-pathogen interaction. Front Cell Infect Microbiol 2013;3:108.
  7. Kamizono A, Nishizawa M, Teranishi Y, Murata K, Kimura A. Identification of a gene conferring resistance to zinc and cadmium ions in the yeast Saccharomyces cerevisiae. Mol Gen Genet 1989;219:161-7.
  8. Miyabe S, Izawa S, Inoue Y. The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae. Biochem Biophys Res Commun 2001;282:79-83. https://doi.org/10.1006/bbrc.2001.4522
  9. Conklin DS, McMaster JA, Culbertson MR, Kung C. COT1, a gene involved in cobalt accumulation in Saccharomyces cerevisiae. Mol Cell Biol 1992;12:3678-88. https://doi.org/10.1128/MCB.12.9.3678
  10. MacDiarmid CW, Gaither LA, Eide D. Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. EMBO J 2000;19:2845-55. https://doi.org/10.1093/emboj/19.12.2845
  11. Li L, Kaplan J. The yeast gene MSC2, a member of the cation diffusion facilitator family, affects the cellular distribution of zinc. J Biol Chem 2001;276:5036-43. https://doi.org/10.1074/jbc.M008969200
  12. Ellis CD, MacDiarmid CW, Eide DJ. Heteromeric protein complexes mediate zinc transport into the secretory pathway of eukaryotic cells. J Biol Chem 2005;280:28811-8. https://doi.org/10.1074/jbc.M505500200
  13. Zhao H, Eide D. The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation. Proc Natl Acad Sci U S A 1996;93:2454-8. https://doi.org/10.1073/pnas.93.6.2454
  14. Zhao H, Eide D. The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. J Biol Chem 1996;271:23203-10. https://doi.org/10.1074/jbc.271.38.23203
  15. Wu CY, Bird AJ, Chung LM, Newton MA, Winge DR, Eide DJ. Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae. BMC Genomics 2008;9:370. https://doi.org/10.1186/1471-2164-9-370
  16. Lyons TJ, Gasch AP, Gaither LA, Botstein D, Brown PO, Eide DJ. Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci U S A 2000;97:7957-62. https://doi.org/10.1073/pnas.97.14.7957
  17. Zhao H, Eide DJ. Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional regulation in Saccharomyces cerevisiae. Mol Cell Biol 1997;17:5044-52. https://doi.org/10.1128/MCB.17.9.5044
  18. Gitan RS, Luo H, Rodgers J, Broderius M, Eide D. Zincinduced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation. J Biol Chem 1998;273:28617-24. https://doi.org/10.1074/jbc.273.44.28617
  19. Gitan RS, Eide DJ. Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter. Biochem J 2000;346 Pt 2:329-36. https://doi.org/10.1042/bj3460329
  20. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev 2011;20:156-74. https://doi.org/10.1183/09059180.00001011
  21. Vicentefranqueira R, Moreno MA, Leal F, Calera JA. The zrfA and zrfB genes of Aspergillus fumigatus encode the zinc transporter proteins of a zinc uptake system induced in an acid, zinc-depleted environment. Eukaryot Cell 2005;4:837-48. https://doi.org/10.1128/EC.4.5.837-848.2005
  22. Amich J, Vicentefranqueira R, Mellado E, Ruiz-Carmuega A, Leal F, Calera JA. The ZrfC alkaline zinc transporter is required for Aspergillus fumigatus virulence and its growth in the presence of the Zn/Mn-chelating protein calprotectin. Cell Microbiol 2014;16:548-64. https://doi.org/10.1111/cmi.12238
  23. Moreno MA, Ibrahim-Granet O, Vicentefranqueira R, Amich J, Ave P, Leal F, Latge JP, Calera JA. The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. Mol Microbiol 2007;64:1182-97. https://doi.org/10.1111/j.1365-2958.2007.05726.x
  24. Kim MJ, Kil M, Jung JH, Kim J. Roles of Zinc-responsive transcription factor Csr1 in filamentous growth of the pathogenic yeast Candida albicans. J Microbiol Biotechnol 2008;18:242-7.
  25. Nobile CJ, Nett JE, Hernday AD, Homann OR, Deneault JS, Nantel A, Andes DR, Johnson AD, Mitchell AP. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol 2009;7:e1000133. https://doi.org/10.1371/journal.pbio.1000133
  26. Bottcher B, Palige K, Jacobsen ID, Hube B, Brunke S. Csr1/Zap1 maintains Zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 2015;14:661-70. https://doi.org/10.1128/EC.00078-15
  27. Citiulo F, Jacobsen ID, Miramon P, Schild L, Brunke S, Zipfel P, Brock M, Hube B, Wilson D. Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLoS Pathog 2012;8:e1002777. https://doi.org/10.1371/journal.ppat.1002777
  28. Schneider Rde O, Fogaca Nde S, Kmetzsch L, Schrank A, Vainstein MH, Staats CC. Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. PLoS One 2012;7:e43773. https://doi.org/10.1371/journal.pone.0043773
  29. Schneider Rde O, Diehl C, dos Santos FM, Piffer AC, Garcia AW, Kulmann MI, Schrank A, Kmetzsch L, Vainstein MH, Staats CC. Effects of zinc transporters on Cryptococcus gattii virulence. Sci Rep 2015;5:10104. https://doi.org/10.1038/srep10104