1887

Abstract

Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is suspected to be one of the anti-oxidant enzymes and virulence determinants active in some pathogenic micro-organisms. To elucidate the role of Cu/ZnSOD in the major human fungal pathogen , its gene, designated , was disrupted by the URA-blaster technique. The resulting / mutant showed delayed hyphal growth on Spider medium but could still form hyphae on other solid media or in liquid media, particularly in response to serum. Moreover, the / mutant was more sensitive to menadione, a redox-cycling agent, than the isogenic wild-type strain, although it still showed an adaptive oxidative stress response. Furthermore, the / mutant cells exhibited slow growth in minimal medium when compared to the wild-type cells, but their growth was restored by the addition of lysine to the medium. Interestingly, cells lacking Cu/ZnSOD showed increased susceptibility to macrophage attack and had attenuated virulence in mice. Thus, these results suggest that Cu/ZnSOD is required for the protection of against oxidative stresses and for the full virulence of the organism to be expressed.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-148-11-3705
2002-11-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/micro/148/11/1483705a.html?itemId=/content/journal/micro/10.1099/00221287-148-11-3705&mimeType=html&fmt=ahah

References

  1. Battistoni, A., Donnarumma, G., Greco, R., Valenti, P. & Rotilio, G. ( 1998; ). Overexpression of a hydrogen peroxide-resistant periplasmic Cu,Zn superoxide dismutase protects Escherichia coli from macrophage killing. Biochem Biophys Res Commun 243, 804-807.[CrossRef]
    [Google Scholar]
  2. Bollag, D. M. & Edelstein, S. J. (1991). Immunoblotting. In Protein Methods, pp. 181–211. New York: Willey-Liss.
  3. Broquist, H. P. ( 1971; ). Lysine biosynthesis (yeast). Methods Enzymol 17, 112-129.
    [Google Scholar]
  4. Chang, E. C. & Kosman, D. J. ( 1990; ). O2-dependent methionine auxotrophy in Cu,Zn superoxide dismutase-deficient mutants of Saccharomyces cerevisiae. J Bacteriol 172, 1840-1845.
    [Google Scholar]
  5. Chary, P., Dillon, D., Schroeder, A. L. & Natvig, D. O. ( 1994; ). Superoxide dismutase (sod-1) null mutants of Neurospora crassa: oxidative stress sensitivity, spontaneous mutation rate and response to mutagens. Genetics 137, 723-730.
    [Google Scholar]
  6. Coleman, D. C., Bennett, D. E., Sullivan, D. J., Gallagher, P. J., Henman, M. C., Stanley, M. B. & Russell, R. J. ( 1993; ). Oral Candida in HIV infection and AIDS: new perspectives/new approaches. Crit Rev Microbiol 19, 61-82.[CrossRef]
    [Google Scholar]
  7. Culotta, V. C., Joh, H. D., Lin, S. J., Slekar, K. H. & Strain, J. ( 1995; ). A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. J Biol Chem 270, 29991-29997.[CrossRef]
    [Google Scholar]
  8. Cutler, J. E. ( 1991; ). Putative virulence factors of Candida albicans. Annu Rev Microbiol 45, 187-218.[CrossRef]
    [Google Scholar]
  9. Diez, B., Schleissner, C., Moreno, M. A., Rodriguez, M., Collados, A. & Barredo, J. L. ( 1998; ). The manganese superoxide dismutase from the penicillin producer Penicillium chrysogenum. Curr Genet 33, 387-394.[CrossRef]
    [Google Scholar]
  10. Farrant, J. L, Sansone, A., Canvin, J. R., Pallen, M. J., Langford, P. R., Wallis, T. S., Dougan, G. & Kroll, J. S. ( 1997; ). Bacterial copper- and zinc-cofactored superoxide dismutase contributes to the pathogenesis of systemic salmonellosis. Mol Microbiol 25, 785-796.[CrossRef]
    [Google Scholar]
  11. Fonzi, W. A. & Irwin, M. Y. ( 1993; ). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717-728.
    [Google Scholar]
  12. Fridovich, I. ( 1989; ). Superoxide dismutases. An adaptation to a paramagnetic gas. J Biol Chem 264, 7761-7764.
    [Google Scholar]
  13. Fridovich, I. ( 1995; ). Superoxide radical and superoxide dismutases. Annu Rev Biochem 64, 97-112.[CrossRef]
    [Google Scholar]
  14. Gunasekaran, U., Yang, R. & Gunasekaran, M. ( 1998; ). Regulation of superoxide dismutase synthesis in Candida albicans. Mycopathologia 141, 59-63.[CrossRef]
    [Google Scholar]
  15. Hamilton, A. J. & Holdom, M. D. ( 1999; ). Antioxidant systems in the pathogenic fungi of man and their role in virulence. Med Mycol 37, 375-389.[CrossRef]
    [Google Scholar]
  16. Hong, Z., LoVerde, P. T., Hammarskjöld, M. L. & Rekosh, D. ( 1992; ). Schistosoma mansoni: cloning of a complementary DNA encoding cytosolic Cu/Zn superoxide dismutase and high-yield expression of the enzymatically active gene product in Escherichia coli. Exp Parasitol 75, 308-322.[CrossRef]
    [Google Scholar]
  17. Huh, W.-K., Kim, S.-T., Kim, H., Jeong, G. & Kang, S.-O. ( 2001; ). Deficiency of d-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans. Infect Immun 69, 3939-3946.[CrossRef]
    [Google Scholar]
  18. Hwang, C.-S., Rhie, G.-e., Kim, S.-T., Kim, Y.-R., Huh, W.-K., Baek, Y.-U. & Kang, S.-O. ( 1999; ). Copper- and zinc-containing superoxide dismutase and its gene from Candida albicans. Biochim Biophys Acta 1427, 245-255.[CrossRef]
    [Google Scholar]
  19. Izawa, S., Inoue, Y. & Kimura, A. ( 1995; ). Oxidative stress response in yeast: effect of glutathione on adaptation to hydrogen peroxide stress in Saccharomyces cerevisiae. FEBS Lett 368, 73-76.[CrossRef]
    [Google Scholar]
  20. Jamieson, D. J., Stephen, D. W. S. & Terriere, E. C. ( 1996; ). Analysis of the adaptive oxidative stress response of Candida albicans. FEMS Microbiol Lett 138, 83-88.[CrossRef]
    [Google Scholar]
  21. Kitayama, M. & Togasaki, R. K. ( 1995; ). Purification and cDNA isolation of chloroplastic phosphoglycerate kinase from Chlamydomonas reinhardtii. Plant Physiol 107, 393-400.[CrossRef]
    [Google Scholar]
  22. Lamarre, C., LeMay, J. D., Deslauriers, N. & Bourbonnais, Y. ( 2001; ). Candida albicans expresses an unusual cytoplasmic manganese-containing superoxide dismutase (SOD3 gene product) upon the entry and during the stationary phase. J Biol Chem 276, 43784-43791.[CrossRef]
    [Google Scholar]
  23. Lee, K. L., Buckley, H. R. & Campbell, C. C. ( 1975; ). An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans. Sabouraudia 13, 148-153.[CrossRef]
    [Google Scholar]
  24. Liu, H., Köhler, J. & Fink, G. R. ( 1994; ). Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266, 1723-1725.[CrossRef]
    [Google Scholar]
  25. Liu, X. F., Elashvili, I., Gralla, E. B., Valentine, J. S., Lapinskas, P. & Culotta, V. C. ( 1992; ). Yeast lacking superoxide dismutase. Isolation of genetic suppressors. J Biol Chem 267, 18298-18302.
    [Google Scholar]
  26. Lo, H. J., Köhler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A. & Fink, G. R. ( 1997; ). Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939-949.[CrossRef]
    [Google Scholar]
  27. Manchenko, G. P. (1994). Superoxide dismutase. In Handbook of Detection of Enzymes on Electrophoretic Gels, p. 98. Boca Raton, FL: CRC.
  28. Okado-Matsumoto, A. & Fridovich, I. ( 2001; ). Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem 276, 38388-38393.[CrossRef]
    [Google Scholar]
  29. Rhie, G.-e., Hwang, C.-S., Brady, M. J. & 7 other authors ( 1999; ). Manganese-containing superoxide dismutase and its gene from Candida albicans. Biochim Biophys Acta 1426, 409–419.[CrossRef]
    [Google Scholar]
  30. Rocha, C. R., Schroppel, K., Harcus, D., Marcil, A., Dignard, D., Taylor, B. N., Thomas, D. Y., Whiteway, M. & Leberer, E. ( 2001; ). Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol Biol Cell 12, 3631-3643.[CrossRef]
    [Google Scholar]
  31. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  32. Vázquez-Torres, A. & Balish, E. ( 1997; ). Macrophages in resistance to candidiasis. Microbiol Mol Biol Rev 61, 170-192.
    [Google Scholar]
  33. Wagner, D. K., Collins-Lech, C. & Sohnle, P. G. ( 1986; ). Inhibition of neutrophil killing of Candida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines. Infect Immun 51, 731-735.
    [Google Scholar]
  34. Wilks, K. E., Dunn, K. L. R., Farrant, J. L., Reddin, K. M., Gorringe, A. R., Langford, P. R. & Kroll, J. S. ( 1998; ). Periplasmic superoxide dismutase in meningococcal pathogenicity. Infect Immun 66, 213-217.
    [Google Scholar]
  35. Wysong, D. R., Christin, L., Sugar, A. M., Robbins, P. W. & Diamond, R. D. ( 1998; ). Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect Immun 66, 1953-1961.
    [Google Scholar]
  36. Youn, H.-D., Kim, E.-J., Roe, J.-H., Hah, Y. C. & Kang, S.-O. ( 1996a; ). A novel nickel-containing superoxide dismutase from Streptomyces spp. Biochem J 318, 889-896.
    [Google Scholar]
  37. Youn, H.-D., Youn, H., Lee, J.-W., Yim, Y.-I., Lee, J.-K., Hah, Y. C. & Kang, S.-O. ( 1996b; ). Unique isozymes of superoxide dismutase in Streptomyces griseus. Arch Biochem Biophys 334, 341-348.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-148-11-3705
Loading
/content/journal/micro/10.1099/00221287-148-11-3705
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