1887

Abstract

The vacuolar H-ATPase (V-ATPase) component Vma7p of the human-pathogenic yeast regulates hyphal growth induced by serum and Spider medium and is essential for virulence. In order to characterize the functions of the putative V-ATPase subunit Vma7p of , null mutants were generated. The resulting mutants showed reduced vacuole acidification, which correlated with defective growth at alkaline pH. In addition, defects in degradation of intravacuolar putative endosomal structures were observed. null mutants were sensitive towards the presence of metal ions. It is concluded that the sequestration of toxic ions in the vacuole via a H gradient generated by the V-ATPase is affected. The null mutant strains were avirulent in a mouse model of systemic candidiasis. In addition, null mutants and the null mutant strain of the Vma7p-interacting phosphatidylinositol 3-kinase Vps34p showed similar phenotypes. In summary, the V-ATPase subunit Vma7p is involved in vacuolar ion transport and this transport is required for hyphal growth and virulence of .

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2005-05-01
2024-03-28
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References

  1. Augsten M., Nguyen M., Eck R, Hübner C., Künkel W., Härtl A. 2002; Defective hyphal induction of a Candida albicans phosphatidylinositol 3-phosphate 5-kinase null mutant on solid media does not lead to decreased virulence. Infect Immun 70:4462–4470 [CrossRef]
    [Google Scholar]
  2. Bonangelino C. J., Chavez E. M., Bonifacino J. S. 2002; Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae. Mol Biol Cell 13:2486–2501 [CrossRef]
    [Google Scholar]
  3. Bruckmann A., Wetzker R., Eck R, Künkel W., Härtl A. 2000; A phosphatidylinositol 3-kinase of Candida albicans influences adhesion, filamentous growth and virulence. Microbiology 146:2755–2764
    [Google Scholar]
  4. Bruckmann A., Augsten K., Wetzker R., Eck R, Künkel W. 2001; The deletion of CaVPS34 in the human pathogenic yeast Candida albicans causes defects in vesicle-mediated protein sorting and nuclear segregation. Yeast 18:343–353 [CrossRef]
    [Google Scholar]
  5. Cheng S., Nguyen M. H., Zhang Z., Jia H., Handfield M., Clancy C. J. 2003; Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus. Infect Immun 71:6101–6103 [CrossRef]
    [Google Scholar]
  6. Cutler J. E. 1991; Putative virulence factors of Candida albicans. Annu Rev Microbiol 45:187–218 [CrossRef]
    [Google Scholar]
  7. Eck R., Bruckmann A., Wetzker R., Künkel W. 2000; A phosphatidylinositol 3-kinase of Candida albicans: molecular cloning and characterization. Yeast 16:933–944 [CrossRef]
    [Google Scholar]
  8. Eck R., Nguyen M., Zipfel P. F, Günther J., Künkel W. 2005; The phosphatidylinositol 3-kinase Vps34p of the human pathogenic yeast Candida albicans is a multifunctional protein that interacts with the putative vacuolar H+-ATPase subunit Vma7p. Int J Med Microbiol in press
    [Google Scholar]
  9. Ernst J. F. 2000; Transcription factors in Candida albicans – environmental control of morphogenesis. Microbiology 146:1763–1774
    [Google Scholar]
  10. Fonzi W. A., Irwin M. Y. 1993; Isogenic strain construction and gene mapping in Candida albicans . Genetics 134:717–728
    [Google Scholar]
  11. Forgac M. 2000; Structure, mechanism and regulation of the clathrin-coated vesicle and yeast vacuolar H+-ATPases. J Exp Biol 203:71–80
    [Google Scholar]
  12. Gola S., Martin R., Walther A., Dunkler A., Wendland J. 2003; New modules for PCR-based gene targeting in Candida albicans: rapid and efficient gene targeting using 100 bp of flanking homology region. Yeast 20:1339–1347 [CrossRef]
    [Google Scholar]
  13. Graham L. A., Hill K. J., Stevens T. H. 1994; VMA7 encodes a novel 14-kDa subunit of the Saccharomyces cerevisiae vacuolar H+-ATPase complex. J Biol Chem 269:25974–25977
    [Google Scholar]
  14. Graham L. A., Powell B., Stevens T. H. 2000; Composition and assembly of the yeast vacuolar H+-ATPase complex. J Exp Biol 203:61–70
    [Google Scholar]
  15. Katzmann D. J., Odorizzi G., Emr S. D. 2002; Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol 3:893–905 [CrossRef]
    [Google Scholar]
  16. Köhler J. R., Fink G. R. 1996; Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development. Proc Natl Acad Sci U S A 93:13223–13228 [CrossRef]
    [Google Scholar]
  17. Lay J., Henry L. K., Clifford J., Koltin Y., Bulawa C. E., Becker J. M. 1998; Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies. Infect Immun 66:5301–5306
    [Google Scholar]
  18. 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]
  19. MacDiarmid C. W., Milanick M. A., Eide D. J. 2002; Biochemical properties of vacuolar zinc transport systems of Saccharomyces cerevisiae. J Biol Chem 277:39187–39194 [CrossRef]
    [Google Scholar]
  20. Munn A. L., Riezman H. 1994; Endocytosis is required for the growth of vacuolar H+-ATPase-defective yeast: identification of six new END genes. J Cell Biol 127:373–386 [CrossRef]
    [Google Scholar]
  21. Negredo A., Monteoliva L., Gil C., Pla J., Nombela C. 1997; Cloning, analysis and one-step disruption of the ARG5,6 gene of Candida albicans. Microbiology 143:297–302 [CrossRef]
    [Google Scholar]
  22. Nelson H., Mandiyan S., Nelson N. 1994; The Saccharomyces cerevisiae VMA7 gene encodes a 14-kDa subunit of the vacuolar H+-ATPase catalytic sector. J Biol Chem 269:24150–24155
    [Google Scholar]
  23. Odds F. C. 1994; Pathogenesis of Candida infections. J Am Acad Dermatol 31:S2–S5 [CrossRef]
    [Google Scholar]
  24. Palmer G. E., Cashmore A., Sturtevant J. 2003; Candida albicans VPS11 is required for vacuole biogenesis and germ tube formation. Eukaryot Cell 2:411–421 [CrossRef]
    [Google Scholar]
  25. Perzov N., Nelson H., Nelson N. 2000; Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants. J Biol Chem 275:40088–40095 [CrossRef]
    [Google Scholar]
  26. Perzov N., Padler-Karavani V., Nelson H., Nelson N. 2002; Characterization of yeast V-ATPase mutants lacking Vph1p or Stv1p and the effect on endocytosis. J Exp Biol 205:1209–1219
    [Google Scholar]
  27. Peto R., Pike M. C., Armitage P. & 7 other authors; 1977; Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39 [CrossRef]
    [Google Scholar]
  28. Roberts C. J., Raymond C. K., Yamashiro C. T., Stevens T. H. 1991; Methods for studying the yeast vacuole. Methods Enzymol 194:644–661
    [Google Scholar]
  29. Sautin Y. Y., Lu M., Gaugler A., Zhang L., Gluck S. L. 2005; Phosphatidylinositol 3-kinase-mediated effects of glucose on vacuolar H+-ATPase assembly, translocation, and acidification of intracellular compartments in renal epithelial cells. Mol Cell Biol 25:575–589 [CrossRef]
    [Google Scholar]
  30. Sonneborn A., Gerads M., Kurpanek K., Sanglard D., Ernst J. F, Bockmühl D. P. 2000; Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol 35:386–396 [CrossRef]
    [Google Scholar]
  31. Stevens T. H., Forgac M. 1997; Structure, function and regulation of the vacuolar (H+)-ATPase. Annu Rev Cell Dev Biol 13:779–808 [CrossRef]
    [Google Scholar]
  32. Teter S. A., Klionsky D. J. 2000; Transport of proteins to the yeast vacuole: autophagy, cytoplasm-to-vacuole targeting, and role of the vacuole in degradation. Semin Cell Dev Biol 11:173–179 [CrossRef]
    [Google Scholar]
  33. Theiss S., Kretschmar M., Nichterlein T., Hof H., Agabian N., Hacker J., Kohler G. A. 2002; Functional analysis of a vacuolar ABC transporter in wild-type Candida albicans reveals its involvement in virulence. Mol Microbiol 43:571–584 [CrossRef]
    [Google Scholar]
  34. Tomashek J. J., Sonnenburg J. L., Artimovich J. M., Klionsky D. J. 1996; Resolution of subunit interactions and cytoplasmic subcomplexes of the yeast vacuolar proton-translocating ATPase. J Biol Chem 271:10397–10404 [CrossRef]
    [Google Scholar]
  35. Underwood E. J. 1977 Trace Elements in Human and Animal Nutrition London: Academic Press;
    [Google Scholar]
  36. Vida T. A., Emr S. D. 1995; A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. J Cell Biol 128:779–792 [CrossRef]
    [Google Scholar]
  37. Vida T. A., Huyer G., Emr S. D. 1993; Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment. J Cell Biol 121:1245–1256 [CrossRef]
    [Google Scholar]
  38. 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 [CrossRef]
    [Google Scholar]
  39. Wendland B., McCaffery J. M., Xiao Q., Emr S. D. 1996; A novel fluorescence-activated cell sorter-based screen for yeast endocytosis mutants identifies a yeast homologue of mammalian Eps15. J Cell Biol 135:1485–1500 [CrossRef]
    [Google Scholar]
  40. 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]
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