Two glutathione peroxidases in the fungal pathogen are expressed in the presence of specific substrates Free

Abstract

Glutathione peroxidases catalyse the reduction of peroxides by reduced glutathione. To determine if these enzymes are important for resistance to oxidative stress and evasion of the innate immune system by the fungal pathogen , two glutathione peroxidase homologues, which share 38 % identity, were identified and investigated. In this study, these peroxidases, Gpx1 and Gpx2, their localization, their contribution to total glutathione peroxidase activity, and their importance to the oxidative and nitrosative stress resistance of are described. It is shown that the two glutathione peroxidase genes are differentially expressed in response to stress. While both and are induced during -butylhydroperoxide or cumene hydroperoxide stress and repressed during nitric oxide stress, only is induced in response to hydrogen peroxide stress. Deletion mutants of each and both of the glutathione peroxidases were generated, and it was found that they are sensitive to various peroxide stresses while showing wild-type resistance to other oxidant stresses, such as superoxide and nitric oxide. While the glutathione peroxidase mutants are slightly sensitive to oxidant killing by macrophages, they exhibit wild-type virulence in a mouse model of cryptococcosis.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.28132-0
2005-08-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/151/8/mic1512573.html?itemId=/content/journal/micro/10.1099/mic.0.28132-0&mimeType=html&fmt=ahah

References

  1. Arteel G. E., Briviba K., Sies H. 1999; Protection against peroxynitrite. FEBS Lett 445:226–230 [CrossRef]
    [Google Scholar]
  2. Arthur J. R. 2000; The glutathione peroxidases. Cell Mol Life Sci 57:1825–1835
    [Google Scholar]
  3. Avery A. M., Avery S. V. 2001; Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases. J Biol Chem 276:33730–33735 [CrossRef]
    [Google Scholar]
  4. Brenot A., King K. Y., Janowiak B., Griffith O., Caparon M. G. 2004; Contribution of glutathione peroxidase to the virulence of Streptococcus pyogenes. Infect Immun 72:408–413 [CrossRef]
    [Google Scholar]
  5. Chen J. W., Dodia C., Feinstein S. I., Jain M. K., Fisher A. B. 2000; 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. J Biol Chem 275:28421–28427 [CrossRef]
    [Google Scholar]
  6. Collinson E. J., Wheeler G. L., Garrido E. O., Avery A. M., Avery S. V., Grant C. M. 2002; The yeast glutaredoxins are active as glutathione peroxidases. J Biol Chem 277:16712–16717 [CrossRef]
    [Google Scholar]
  7. Cox G. M., Mukherjee J., Cole G. T., Casadevall A., Perfect J. R. 2000; Urease as a virulence factor in experimental cryptococcosis. Infect Immun 68:443–448 [CrossRef]
    [Google Scholar]
  8. Cox G. M., Harrison T. S., McDade H. C., Taborda C. P., Heinrich G., Casadevall A., Perfect J. R. 2003; Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun 71:173–180 [CrossRef]
    [Google Scholar]
  9. Davidson R. C., Blankenship J. R., Kraus P. R., de Jesus Berrios M., Hull C. M., D'Souza C., Wang P., Heitman J. 2002; A PCR-based strategy to generate integrative targeting alleles with large regions of homology. Microbiology 148:2607–2615
    [Google Scholar]
  10. de Jesus-Berrios M., Liu L., Nussbaum J. C., Cox G. M., Stamler J. S., Heitman J. 2003; Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol 13:1963–1968 [CrossRef]
    [Google Scholar]
  11. Delaunay A., Pflieger D., Barrault M. B., Vinh J., Toledano M. B. 2002; A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 111:471–481 [CrossRef]
    [Google Scholar]
  12. Dickinson D. A., Forman H. J. 2002; Cellular glutathione and thiols metabolism. Biochem Pharm 64:1019–1026 [CrossRef]
    [Google Scholar]
  13. Fujimura H., Sakuma Y. 1993; Simplified isolation of chromosomal and plasmid DNA from yeasts. Biotechniques 14:538–540
    [Google Scholar]
  14. Giles S. S., Perfect J. R., Cox G. M. 2005; Cytochrome c peroxidase contributes to the antioxidant defense of Cryptococcus neoformans. Fungal Genet Biol 42:20–29 [CrossRef]
    [Google Scholar]
  15. Hua J. H., Meyer J. D., Lodge J. K. 2000; Development of positive selectable markers for the fungal pathogen. Cryptococcus neoformans. Clin Diagn Lab Immunol 7:125–128
    [Google Scholar]
  16. Inoue Y., Matsuda T., Sugiyama K., Izawa S., Kimura A. 1999; Genetic analysis of glutathione peroxidase in oxidative stress response of. Saccharomyces cerevisiae. J Biol Chem 274:27002–27009 [CrossRef]
    [Google Scholar]
  17. Loftus B. J., Fung E., Roncaglia P. 51 other authors 2005; The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 307:1321–1324 [CrossRef]
    [Google Scholar]
  18. McDade H. C., Cox G. M. 2001; A new dominant selectable marker for use in Cryptococcus neoformans. Med Mycol 39:151–154 [CrossRef]
    [Google Scholar]
  19. Missall T. A., Lodge J. K. 2005; Thioredoxin reductase is essential for viability in the fungal pathogen. Cryptococcus neoformans. Eukaryot Cell 4:487–489 [CrossRef]
    [Google Scholar]
  20. Missall T. A., Lodge J. K., McEwen J. E. 2004a; Mechanisms of resistance to oxidative and nitrosative stress: implications for fungal survival in mammalian hosts. Eukaryot Cell 3:835–846 [CrossRef]
    [Google Scholar]
  21. Missall T. A., Pusateri M. E., Lodge J. K. 2004b; Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen. Cryptococcus neoformans. Mol Microbiol 51:1447–1458 [CrossRef]
    [Google Scholar]
  22. Missall T. A., Moran J. M., Corbett J. A., Lodge J. K. 2005; Distinct stress responses of two functional laccases in Cryptococcus neoformans are revealed in the absence of the thiol-specific antioxidant, Tsa1. Eukaryot Cell 4:202–208 [CrossRef]
    [Google Scholar]
  23. Nelson R. T., Pryor B. A., Lodge J. K. 2003; Sequence length required for homologous recombination in Cryptococcus neoformans. Fungal Genet Biol 38:1–9 [CrossRef]
    [Google Scholar]
  24. Schlecker T., Schmidt A., Dirdjaja N., Voncken F., Clayton C., Krauth-Siegel R. L. 2005; Substrate specificity, localisation and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in. Trypanosoma brucei. J Biol Chem 280:14385–14394 [CrossRef]
    [Google Scholar]
  25. Steen B. R., Zuyderduyn S., Toffaletti D. L., Marra M., Jones S. J. M., Perfect J. R., Kronstad J. 2003; Cryptococcus neoformans gene expression during experimental cryptococcal meningitis. Eukaryot Cell 2:1336–1349 [CrossRef]
    [Google Scholar]
  26. Toffaletti D. L., Rude T. H., Johnston S. A., Durack D. T., Perfect J. R. 1993; Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol 175:1405–1411
    [Google Scholar]
  27. Trotter E. W., Grant C. M. 2003; Non-reciprocal regulation of the redox state of the glutathione-glutaredoxin and thioredoxin systems. EMBO Rep 4:184–188 [CrossRef]
    [Google Scholar]
  28. Tsuzi D., Maeta K., Takatsume Y., Izawa S., Inoue Y. 2004; Regulation of the yeast phospholipid hydroperoxide glutathione peroxidase GPX2 by oxidative stress is mediated by Yap1 and Skn7. FEBS Lett 565:148–154 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.28132-0
Loading
/content/journal/micro/10.1099/mic.0.28132-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed