1887

Abstract

Summary: , the most important human fungal pathogen, is a dimorphic fungus that can grow either as a yeast or as a hyphal form in response to medium conditions. A RAS-related C. albicans gene () was isolated as a suppressor of a bud-emergence mutation of the baker's yeast, . The deduced protein encoded by is 248 amino acids long and 56% identical to that encoded by the 5. cerevisiae RSRl (BUDI) gene. Disruption of CaRSRl in C. albicans indicated that CaRSRl is involved in both yeast and hypha development. In the yeast phase, CaRSRl is required for normal (polar) bud site selection and is involved in cell morphogenesis; in the yeast-mycelial transition it is involved in germ tube emergence; and in the development of the hyphae it is involved in cell elongation. The disruption of CaRSRl leads to reduced virulence in both heterozygote and homozygote disruptants in a dose-dependent manner. The reduced virulence can be attributed to the reduced germination and shorter hyphae resulting from the disruption of CaRSRl.

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1997-09-01
2024-03-28
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References

  1. Adams A. E. M., Johnson D. I., Longnecker R. M., Sloat B. F., Pringle J. R. 1990; CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae . J Cell Biol 111:131–142
    [Google Scholar]
  2. Alani E., Liang C., Kleckner N. 1987; A method for gene disruption that allows repeated use of URA3 selection in construction of multicopy disrupted yeast strains. Genetics 116:541–545
    [Google Scholar]
  3. Bender A. 1993; Genetic evidence for the roles of the bud-site-selection genes BUD5 and BUD2 in control of the Rsr1 (Bud1p) GTPase in yeast. Proc Natl Acad Sci USA 90:9926–9929
    [Google Scholar]
  4. Bender A., Pringle J. R. 1989; Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1 . Proc Natl Acad Sci USA 86:9976–9980
    [Google Scholar]
  5. Benton B. K., Tinkelberg A. H., Jean D., Plump S. D., Cross F. R. 1993; Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J 12:5267–5275
    [Google Scholar]
  6. Boeke J. D., Lacroute F., Fink G. R. 1984; A positive selection for mutants lacking orotidine-5ʹ-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet 197:345–346
    [Google Scholar]
  7. Bulawa C. E., Miller D. W., Henry L. K., Becker J. M. 1995; Reduced virulence of chitin-deficient mutants of Candida albicans . Proc Natl Acad Sci USA 92:10570–10574
    [Google Scholar]
  8. Burke J. R., Enghild J. J., Martin M. E., Jou Y.-S., Myers R. M., Roses A. D., Vance J. M., Strittmatter W. J. 1996; Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat Med 2:347–350
    [Google Scholar]
  9. Cannon R. C., Jenkinson H. F., Shepherd M. G. 1990; Cloning and expression of Candida albicans ADE2 and proteinase genes on a replicative plasmid in C. albicans and in Saccharomyces cerevisiae . Mol Gen Genet 235:453–457
    [Google Scholar]
  10. Chaffin W. L. 1984; Site selection for bud and germ tube emergence in Candida albicans . J Gen Microbiol 130:431–440
    [Google Scholar]
  11. Chang E. C., Barr M., Wang Y., Jung V., Xu H.-P., Wigler M. H. 1994; Cooperative interaction of S. pombe proteins required for mating and morphogenesis. Cell 79:131–141
    [Google Scholar]
  12. Chenevert J., Corrado K., Bender A., Pringle J., Herskowitz I. 1992; A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains. Nature 356:77–79
    [Google Scholar]
  13. Chenevert J., Valtz N., Herskowitz I. 1994; Identification of genes required for normal pheromone-induced cell polarization in Saccharomyces cerevisiae . Genetics 136:1287–1297
    [Google Scholar]
  14. Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. 1992; Multifunctional yeast high-copy-number shuttle vectors. Gene 110:119–122
    [Google Scholar]
  15. Coleman K. G., Steensma H. Y., Kaback D. B., Pringle J. R. 1986; Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation and characterization of the CDC24 gene and adjacent regions of the chromosome. Mol Cell Biol 6:4516–4525
    [Google Scholar]
  16. Courey A. J., Holtzman D. A., Jackson S. P., Tjian R. 1989; Synergistic activation by the glutamine rich domains of human transcription factor Sp1. Cell 59:827–836
    [Google Scholar]
  17. Cutler J. E. 1991; Putative virulence factors of Candida albicans . Annu Rev Microbiol 45:187–218
    [Google Scholar]
  18. Cvrcková A., De Virgilio C., Manser E., Pringle J. R., Nasmyth K. 1995; Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast. Genes Dev 9:1817–1830
    [Google Scholar]
  19. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12:387–395
    [Google Scholar]
  20. Fonzi W. A., Irwin M. W. 1993; Isogenic strain construction and gene mapping in Candida albicans . Genetics 134:717–728
    [Google Scholar]
  21. Fukui Y., Kozasa T., Kaziro Y., Takeda T., Yamamoto M. 1986; Role of a ras homolog in the life cycle of Schizosaccharomyces pombe . Cell 44:329–336
    [Google Scholar]
  22. Gillum A. M., Tsay E. Y. H., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5ʹ-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179–192
    [Google Scholar]
  23. Gimeno C. J., Ljungdhal P. O., Styles C. A., Fink G. R. 1992; Unipolar cell divisions in the yeast Saccharomyces cerevisiae lead to filamentous growth: regulation by starvation and RAS . Cell 68:1077–1090
    [Google Scholar]
  24. Guo Z., Sherman F. 1995; 3ʹ-End-forming signals of yeast mRNA. Mol Cell Biol 15:5983–5990
    [Google Scholar]
  25. Hartwell L. H., Mortimer R. K., Culotti J., Culotti M. 1973; Genetic control of the cell division cycle in yeast. V. Genetic analysis of cdc mutants. Genetics 74:267–286
    [Google Scholar]
  26. Herskowitz I., Park H.-O., Sanders S., Valtz N., Peter M. 1995; Programming of cell polarity in budding yeast by endogenous and exogenous signals. Cold Spring Harbor Symp Quant Biol 60:717–727
    [Google Scholar]
  27. Hoffman C. S., Winston F. 1987; A ten minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of E. coli . Gene 57:267–272
    [Google Scholar]
  28. Ito H., Fukuda Y., Murata K., Kimura A. 1983; Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153:163–168
    [Google Scholar]
  29. Johnson D. I., Pringle J. R. 1990; Molecular characterization of CDC42, a S. cerevisiae gene involved in the development of cell polarity. J Cell Biol 111:143–152
    [Google Scholar]
  30. Köhler J. R., Fink G. R. 1996; Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signalling components have defects in hyphal development. Proc Natl Acad Sci USA 93:13223–13228
    [Google Scholar]
  31. Kwon-Chung K. J., Bennett J. 1992 Medical Mycology pp. 816–817 Philadelphia, PA: Lea & Fabiger;
    [Google Scholar]
  32. Langford C. J., Klinz F. J., Donath C., Gallwitz D. 1984; Point mutations identify the conserved, intron contained TACTAAC as an essential splicing signal sequence in yeast. Cell 36:645–653
    [Google Scholar]
  33. Leberer E., Harcus D., Broadbent I. D., Clark K. L., Dignard D., Ziegelbauer K., Schmidt A., Gow N. A. R., Brown A. J. P., Thomas D. Y. 1996; Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans . Proc Natl Acad Sci USA 93:13217–13222
    [Google Scholar]
  34. 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
    [Google Scholar]
  35. Liu H., Köhler J., Fink G. R. 1994; Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266:1723–1726
    [Google Scholar]
  36. Lowy D. R., Willumsen B. M. 1993; Function and regulation of RAS. Annu Rev Biochem 62:851–891
    [Google Scholar]
  37. Maeda H., Ishida N. 1967; Specificity of binding hexo-pyranosyl polysaccharides with fluorescent brightener. J Biochem 62:276–278
    [Google Scholar]
  38. Marck C. 1988; DNA Strider: a ‘C’ program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers. Nucleic Acids Res 16:1829–1836
    [Google Scholar]
  39. Marcus S., Polverino A., Chang E., Robbins D., Cobb M. H., Wigler M. H. 1995; Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases, is a component of a Ras/Cdc42 signalling module in the fission yeast Schizosaccharomyces pombe . Proc Natl Acad Sci USA 92:6180–6184
    [Google Scholar]
  40. Matsui Y., Kikuchi A., Kawata M., Kondo J., Teranishi Y., Takai Y. 1990; Molecular cloning of smg p21B and identification of smg p21 purified from bovine brain and human platelets as smg 21B. Biochem Biophys Res Commun 166:1010–1016
    [Google Scholar]
  41. Michelitch M., Chant J. 1996; A mechanism of Bud1p GTPase action suggested by mutational analysis and immunolocalization. Curr Biol 6:446–454
    [Google Scholar]
  42. Mischke D. M., Chant J. 1995; The shape of things to come: morphogenesis in yeast and related patterns in other systems. Can J Bot 73 (Suppl. 1)234–242
    [Google Scholar]
  43. Morishita T., Mitsuzawa H., Nakafuku M., Nakamura S., Hattori S., Anraku Y. 1995; Requirement of Saccharomyces cerevisiae Ras for completion of mitosis. Science 270:1213–1215
    [Google Scholar]
  44. Ngsee J. K., Elferink L. A., Scheller R. H. 1991; A family of ras-like GTP-binding proteins expressed in electromotor neurons. J Biol Chem 266:2675–2680
    [Google Scholar]
  45. Odds F. C., Cockayne A., Hayward J., Abbot A. B. 1985; Effects of imidazole- and triazole-derivative antifungal compounds on the growth and morphological development of Candida albicans hyphae. J Gen Microbiol 131:2581–2589
    [Google Scholar]
  46. Ottilie S., Miller P. J., Johnson D. I., Creasy C. L., Sells M. A., Bagrodia. S., Forsburg S. L., Chernoff J. 1995; Fission yeast pak1 + encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating. EMBO J 14:5908–5919
    [Google Scholar]
  47. Roemer T., Vallier L. G., Snyder M. 1996; Selection of polarised growth sites in yeast. Trends Cell Biol 6:431–438
    [Google Scholar]
  48. Rosenbluh A., Mevarech M., Koltin Y., Gorman J. A. 1985; Isolation of genes from Candida albicans by complementation in Saccharomyces cerevisiae . Mol Gen Genet 200:500–502
    [Google Scholar]
  49. Ruggieri R., Bender A., Matsui Y., Powers S., Takai Y., Pringle J. R., Matsumoto K. 1992; RSR1, a ras-like gene homologous to Krev-1 (smg21A/rap1A): role in the development of cell polarity and interactions with the Ras pathway in Saccharomyces cerevisiae . Mol Cell Biol 12:758–766
    [Google Scholar]
  50. Russo P., Li W.-Z., Hampsey D. M., Zaret K. S., Sherman F. 1991; Distinct cis-acting signals enhance 3ʹ end point formation of CYC1 mRNA in the yeast Saccharomyces cerevisiae . EMBO J 10:563–571
    [Google Scholar]
  51. Russo P., Li W.-Z., Guo Z., Sherman F. 1993; Signals that produce 3ʹ termini in CYC1 mRNA of the yeast Saccharomyces cerevisiae . Mol Cell Biol 13:7836–7849
    [Google Scholar]
  52. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual 2nd edn Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  53. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
    [Google Scholar]
  54. Schafer W. R., Rine J. 1992; Protein prenylation genes, enzymes, targets and functions. Annu Rev Genet 30:209–237
    [Google Scholar]
  55. Sherman F. 1991; Getting started with yeast. Methods Enzymol 194:3–21
    [Google Scholar]
  56. Sloat B., Adams A., Pringle J. 1981; Roles of the CDC24 gene product in cellular morphogenesis during the S. cerevisiae cell cycle. J Cell Biol 89:395–405
    [Google Scholar]
  57. Smith H. A., Allaudeen H. S., Whitman M. H., Koltin Y., Gorman A. G. 1988; Isolation and characterization of a β-tubulin gene from Candida albicans. . Gene 63:53–63
    [Google Scholar]
  58. Staebell M., Soll D. R. 1985; Temporal and spatial differences in cell wall expansion during bud and mycelium formation in Candida albicans . J Gen Microbiol 131:1467–1480
    [Google Scholar]
  59. Sternberg N., Sauer B., Hoess R., Abremski K. 1986; Bacteriophage P1 cre gene and its regulatory region. Evidence for multiple promoters and for regulation by DNA methylation. J Mol Biol 187:197–212
    [Google Scholar]
  60. Stott K., Blackburn J. M., Butler P. J. G., Perutz M. 1995; Incorporation of glutamine repeats makes protein oligomerize: implications for neurodegenerative diseases. Proc Natl Acad Sci USA 92:6509–6513
    [Google Scholar]
  61. Valencia A., Chardin P., Wittinghofer A., Sander C. 1991; The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry 30:4637–4648
    [Google Scholar]
  62. Zheng Y., Cerione R., Bender A. 1994; Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3. J Biol Chem 269:2369–2372
    [Google Scholar]
  63. Zheng Y., Bender A., Cerione R. A. 1995; Interactions among proteins involved in bud-site selection and bud-site assembly in Saccharomyces cerevisiae . J Biol Chem 270:626–630
    [Google Scholar]
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