1887

Abstract

We have previously shown that copper uptake and regulation in the opportunistic pathogen has some similarities to those in , including the activation of the copper transporter gene under low-copper conditions by the transcription factor CaMac1p. However, in this study, further analysis has shown that the actual mechanism of regulation by CaMac1p is different from that of its homologue. We demonstrate for the first time, to our knowledge, that the gene is transcriptionally autoregulated in a copper-dependent manner, in contrast to , which is constitutively transcribed. We also demonstrate that the presence of one copper response element in the promoters of , and the ferric/cupric reductase gene is sufficient for normal levels of copper-responsive transcription. In contrast, two promoter elements are essential for normal levels of copper-dependent transcriptional activation by ScMac1p. CaMac1p is also involved in the regulation of the iron-responsive transcriptional repressor gene and the alternative oxidase gene . This work describes a key feature of the copper uptake system in that distinguishes it from similar processes in the model yeast . The importance of copper uptake in the environment of the human host and the implications for the disease process are discussed.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2007/013441-0
2008-05-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/154/5/1502.html?itemId=/content/journal/micro/10.1099/mic.0.2007/013441-0&mimeType=html&fmt=ahah

References

  1. Abramoff M. D., Magelhaes P. J., Ram S. J. 2004; Image processing with Image J. Biophotonics Int 11:36–42
    [Google Scholar]
  2. Bensen E. S., Martin S. J., Li M., Berman J., Davis D. A. 2004; Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. Mol Microbiol 54:1335–1351
    [Google Scholar]
  3. Borghouts C., Werner A., Elthon T., Osiewacz H. D. 2001; Copper-modulated gene expression and senescence in the filamentous fungus Podospora anserina . Mol Cell Biol 21:390–399
    [Google Scholar]
  4. Braun B. R., van Het Hoog M., d'Enfert C., Martchenko M., Dungan J., Kuo A., Inglis D. O., Uhl M. A., Hogues H. other authors 2005; A human-curated annotation of the Candida albicans genome. PLoS Genet 1:36–57
    [Google Scholar]
  5. Crichton R. R., Pierre J. L. 2001; Old iron, young copper: from Mars to Venus. Biometals 14:99–112
    [Google Scholar]
  6. De Freitas J. M., Kim J. H., Poynton H., Su T., Wintz H., Fox T., Holman P., Loguinov A., Keles S. other authors 2004; Exploratory and confirmatory gene expression profiling of mac1 Δ. J Biol Chem 279:4450–4458
    [Google Scholar]
  7. Downie J. A., Garland P. B. 1973; An antimycin A- and cyanide-resistant variant of Candida utilis arising during copper-limited growth. Biochem J 134:1051–1061
    [Google Scholar]
  8. Eck R., Hundt S., Hartl A., Roemer E., Kunkel W. 1999; A multicopper oxidase gene from Candida albicans : cloning, characterization and disruption. Microbiology 145:2415–2422
    [Google Scholar]
  9. Filler S. G., Ibe B. O., Ibrahim A. S., Ghannoum M. A., Raj J. U., Edwards J. E. Jr 1994; Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis. Infect Immun 62:1064–1069
    [Google Scholar]
  10. Gietz R. D., Woods R. A. 2002; Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350:87–96
    [Google Scholar]
  11. Gillum A. M., Tsay E. Y., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179–182
    [Google Scholar]
  12. Gross C., Kelleher M., Iyer V. R., Brown P. O., Winge D. R. 2000; Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays. J Biol Chem 275:32310–32316
    [Google Scholar]
  13. Gudlaugsson O., Gillespie S., Lee K., Vande Berg J., Hu J., Messer S., Herwaldt L., Pfaller M., Diekema D. 2003; Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37:1172–1177
    [Google Scholar]
  14. Huang G.-H., Nie X.-Y., Chen J.-Y. 2006; CaMac1, a Candida albicans copper ion-sensing transcription factor, promotes filamentous and invasive growth in Saccharomyces cerevisiae . Acta Biochim Biophys Sin (Shanghai) 38:213–217
    [Google Scholar]
  15. Huh W. K., Kang S. O. 2001; Characterization of the gene family encoding alternative oxidase from Candida albicans . Biochem J 356:595–604
    [Google Scholar]
  16. Hwang C. S., Rhie G. E., Oh J. H., Huh W. K., Yim H. S., Kang S. O. 2002; Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence. Microbiology 148:3705–3713
    [Google Scholar]
  17. Jensen L. T., Posewitz M. C., Srinivasan C., Winge D. R. 1998; Mapping of the DNA binding domain of the copper-responsive transcription factor Mac1 from Saccharomyces cerevisiae . J Biol Chem 273:23805–23811
    [Google Scholar]
  18. Knight S. A., Lesuisse E., Stearman R., Klausner R. D., Dancis A. 2002; Reductive iron uptake by Candida albicans : role of copper, iron and the TUP1 regulator. Microbiology 148:29–40
    [Google Scholar]
  19. Labbé S., Zhu Z., Thiele D. J. 1997; Copper-specific transcriptional repression of yeast genes encoding critical components in the copper transport pathway. J Biol Chem 272:15951–15958
    [Google Scholar]
  20. Lan C. Y., Rodarte G., Murillo L. A., Jones T., Davis R. W., Dungan J., Newport G., Agabian N. 2004; Regulatory networks affected by iron availability in Candida albicans . Mol Microbiol 53:1451–1469
    [Google Scholar]
  21. Levitin A., Whiteway M. 2007; The effect of prostaglandin E2 on transcriptional responses of Candida albicans . Microbiol Res 162:201–210
    [Google Scholar]
  22. Liu X. D., Thiele D. J. 1997; Yeast metallothionein gene expression in response to metals and oxidative stress. Methods 11:289–299
    [Google Scholar]
  23. Lorenz M. C., Bender J. A., Fink G. R. 2004; Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076–1087
    [Google Scholar]
  24. Mandel M., Higa A. 1970; Calcium-dependent bacteriophage DNA infection. J Mol Biol 53:159–162
    [Google Scholar]
  25. Martins L. J., Jensen L. T., Simon J. R., Keller G. L., Winge D. R. 1998; Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae . J Biol Chem 273:23716–23721
    [Google Scholar]
  26. Marvin M. E., Williams P. H., Cashmore A. M. 2003; The Candida albicans CTR1 gene encodes a functional copper transporter. Microbiology 149:1461–1474
    [Google Scholar]
  27. Marvin M. E., Mason R. P., Cashmore A. M. 2004; The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1 . Microbiology 150:2197–2208
    [Google Scholar]
  28. Murad A. M., Lee P. R., Broadbent I. D., Barelle C. J., Brown A. J. 2000; CIp10, an efficient and convenient integrating vector for Candida albicans . Yeast 16:325–327
    [Google Scholar]
  29. Navarro-Garcia F., Sanchez M., Nombela C., Pla J. 2001; Virulence genes in the pathogenic yeast Candida albicans . FEMS Microbiol Rev 25:245–268
    [Google Scholar]
  30. Pfaller M. A., Diekema D. J. 2002; Role of sentinel surveillance of candidemia: trends in species distribution and antifungal susceptibility. J Clin Microbiol 40:3551–3557
    [Google Scholar]
  31. Ramanan N., Wang Y. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062–1064
    [Google Scholar]
  32. Riggle P. J., Kumamoto C. A. 2000; Role of a Candida albicans P1-type ATPase in resistance to copper and silver ion toxicity. J Bacteriol 182:4899–4905
    [Google Scholar]
  33. Rupp S. 2002; LacZ assays in yeast. Methods Enzymol 350:112–131
    [Google Scholar]
  34. Schaible U. E., Kaufmann S. H. 2004; Iron and microbial infection. Nat Rev Microbiol 2:946–953
    [Google Scholar]
  35. Schmitt M. E., Brown T. A., Trumpower B. L. 1990; A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae . Nucleic Acids Res 18:3091–3092
    [Google Scholar]
  36. Stearman R., Yuan D. S., Yamaguchi-Iwai Y., Klausner R. D., Dancis A. 1996; A permease–oxidase complex involved in high-affinity iron uptake in yeast. Science 271:1552–1557
    [Google Scholar]
  37. Tirosh I., Berman J., Barkai N. 2007; The pattern and evolution of yeast promoter bendability. Trends Genet 23:318–321
    [Google Scholar]
  38. Tortorano A. M., Peman J., Bernhardt H., Klingspor L., Kibbler C. C., Faure O., Biraghi E., Canton E., Zimmermann K. other authors 2004; Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23:317–322
    [Google Scholar]
  39. Tsukihara T., Aoyama H., Yamashita E., Tomizaki T., Yamaguchi H., Shinzawa-Itoh K., Nakashima R., Yaono R., Yoshikawa S. 1995; Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 Å. Science 269:1069–1074
    [Google Scholar]
  40. Urbanski N. K., Beresewicz A. 2000; Generation of •OH initiated by interaction of Fe2+ and Cu+ with dioxygen; comparison with the Fenton chemistry. Acta Biochim Pol 47:951–962
    [Google Scholar]
  41. Weissman Z., Berdicevsky I., Cavari B. Z., Kornitzer D. 2000; The high copper tolerance of Candida albicans is mediated by a P-type ATPase. Proc Natl Acad Sci U S A 97:3520–3525
    [Google Scholar]
  42. Wickerham L. J. 1946; A critical evaluation of the nitrogen assimilation tests commonly used in the classification of yeasts. J Bacteriol 52:293–301
    [Google Scholar]
  43. Wilson R. B., Davis D., Mitchell A. P. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181:1868–1874
    [Google Scholar]
  44. Wisplinghoff H., Bischoff T., Tallent S. M., Seifert H., Wenzel R. P., Edmond M. B. 2004; Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317
    [Google Scholar]
  45. Xu Z., Zhang L. X., Zhang J. D., Cao Y. B., Yu Y. Y., Wang D. J., Ying K., Chen W. S., Jiang Y. Y. 2006; cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients. Int J Med Microbiol 296:421–434
    [Google Scholar]
  46. Yamaguchi-Iwai Y., Serpe M., Haile D., Yang W., Kosman D. J., Klausner R. D., Dancis A. 1997; Homeostatic regulation of copper uptake in yeast via direct binding of MAC1 protein to upstream regulatory sequences of FRE1 and CTR1 . J Biol Chem 272:17711–17718
    [Google Scholar]
  47. Zhu Z., Labbé S., Pena M. M., Thiele D. J. 1998; Copper differentially regulates the activity and degradation of yeast Mac1 transcription factor. J Biol Chem 273:1277–1280
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2007/013441-0
Loading
/content/journal/micro/10.1099/mic.0.2007/013441-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error