Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Dec;65(12):4909–4917. doi: 10.1128/iai.65.12.4909-4917.1997

A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans.

R Petter 1, Y C Chang 1, K J Kwon-Chung 1
PMCID: PMC175708  PMID: 9393775

Abstract

The SNF1 gene of Saccharomyces cerevisiae (ScSNF1) is essential for the derepression of catabolic repression. We report here the isolation and characterization of an SNF1 homolog from Candida albicans (CaSNF1) which is apparently essential for the viability of this organism. The putative amino acid sequence of CaSNF1 has 68% identity with that of ScSNF1 and can restore the S. cerevisiae snf1 delta mutant's ability to utilize sucrose. Disruption of one of the CaSNF1 alleles resulted in morphological changes and decreased growth rates but did not modify the carbon source utilization pattern. Repetitive unsuccessful attempts to generate a snf1/snf1 homozygote by disruption of the second allele, using various vectors and approaches, suggest the lethal nature of this mutation. Integration into the second allele was possible only when a full-length functional SNF1 sequence was reassembled, further supporting this hypothesis and indicating that the indispensability of Snf1p prevented the isolation of snf1/snf1 mutants. The mutant bearing two disrupted SNF1 alleles and the SNF1 functional sequence maintained its ability to utilize sucrose and produced stellate colonies with extensive hyphal growth on agar media. It was demonstrated that in a mouse model, the virulences of this mutant and the wild-type strain are similar, suggesting that hyphal growth in vitro is not an indicator for higher virulence.

Full Text

The Full Text of this article is available as a PDF (580.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguan K., Scott J., See C. G., Sarkar N. H. Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals. Gene. 1994 Nov 18;149(2):345–350. doi: 10.1016/0378-1119(94)90174-0. [DOI] [PubMed] [Google Scholar]
  2. Alderson A., Sabelli P. A., Dickinson J. R., Cole D., Richardson M., Kreis M., Shewry P. R., Halford N. G. Complementation of snf1, a mutation affecting global regulation of carbon metabolism in yeast, by a plant protein kinase cDNA. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8602–8605. doi: 10.1073/pnas.88.19.8602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carling D., Aguan K., Woods A., Verhoeven A. J., Beri R. K., Brennan C. H., Sidebottom C., Davison M. D., Scott J. Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. J Biol Chem. 1994 Apr 15;269(15):11442–11448. [PubMed] [Google Scholar]
  4. Celenza J. L., Carlson M. A yeast gene that is essential for release from glucose repression encodes a protein kinase. Science. 1986 Sep 12;233(4769):1175–1180. doi: 10.1126/science.3526554. [DOI] [PubMed] [Google Scholar]
  5. Celenza J. L., Carlson M. Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein. Mol Cell Biol. 1989 Nov;9(11):5034–5044. doi: 10.1128/mcb.9.11.5034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fonzi W. A., Irwin M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. doi: 10.1093/genetics/134.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fujimura H., Sakuma Y. Simplified isolation of chromosomal and plasmid DNA from yeasts. Biotechniques. 1993 Apr;14(4):538–540. [PubMed] [Google Scholar]
  8. Geber A., Williamson P. R., Rex J. H., Sweeney E. C., Bennett J. E. Cloning and characterization of a Candida albicans maltase gene involved in sucrose utilization. J Bacteriol. 1992 Nov;174(21):6992–6996. doi: 10.1128/jb.174.21.6992-6996.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gietz R. D., Schiestl R. H., Willems A. R., Woods R. A. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure. Yeast. 1995 Apr 15;11(4):355–360. doi: 10.1002/yea.320110408. [DOI] [PubMed] [Google Scholar]
  10. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992 Mar 20;68(6):1077–1090. doi: 10.1016/0092-8674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  11. Gow N. A. Growth and guidance of the fungal hypha. Microbiology. 1994 Dec;140(Pt 12):3193–3205. doi: 10.1099/13500872-140-12-3193. [DOI] [PubMed] [Google Scholar]
  12. Gow N. A., Robbins P. W., Lester J. W., Brown A. J., Fonzi W. A., Chapman T., Kinsman O. S. A hyphal-specific chitin synthase gene (CHS2) is not essential for growth, dimorphism, or virulence of Candida albicans. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6216–6220. doi: 10.1073/pnas.91.13.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Halford N. G., Man A. L., Barker J. H., Monger W., Shewry P. R., Smith A., Purcell P. C. Investigating the role of plant SNF1-related protein kinases. Biochem Soc Trans. 1994 Nov;22(4):953–957. doi: 10.1042/bst0220953. [DOI] [PubMed] [Google Scholar]
  14. Hannappel U., Vicente-Carbajosa J., Barker J. H., Shewry P. R., Halford N. G. Differential expression of two barley SNF1-related protein kinase genes. Plant Mol Biol. 1995 Mar;27(6):1235–1240. doi: 10.1007/BF00020898. [DOI] [PubMed] [Google Scholar]
  15. Hardie D. G., Carling D., Halford N. Roles of the Snf1/Rkin1/AMP-activated protein kinase family in the response to environmental and nutritional stress. Semin Cell Biol. 1994 Dec;5(6):409–416. doi: 10.1006/scel.1994.1048. [DOI] [PubMed] [Google Scholar]
  16. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kelly R., Kwon-Chung K. J. A zinc finger protein from Candida albicans is involved in sucrose utilization. J Bacteriol. 1992 Jan;174(1):222–232. doi: 10.1128/jb.174.1.222-232.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kwon-Chung K. J., Wickes B. L., Merz W. G. Association of electrophoretic karyotype of Candida stellatoidea with virulence for mice. Infect Immun. 1988 Jul;56(7):1814–1819. doi: 10.1128/iai.56.7.1814-1819.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laurent B. C., Treich I., Carlson M. Role of yeast SNF and SWI proteins in transcriptional activation. Cold Spring Harb Symp Quant Biol. 1993;58:257–263. doi: 10.1101/sqb.1993.058.01.030. [DOI] [PubMed] [Google Scholar]
  20. Lesage P., Yang X., Carlson M. Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster transcriptional activator: a new role for SNF1 in the glucose response. Mol Cell Biol. 1996 May;16(5):1921–1928. doi: 10.1128/mcb.16.5.1921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Merz W. G. Candida albicans strain delineation. Clin Microbiol Rev. 1990 Oct;3(4):321–334. doi: 10.1128/cmr.3.4.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Muranaka T., Banno H., Machida Y. Characterization of tobacco protein kinase NPK5, a homolog of Saccharomyces cerevisiae SNF1 that constitutively activates expression of the glucose-repressible SUC2 gene for a secreted invertase of S. cerevisiae. Mol Cell Biol. 1994 May;14(5):2958–2965. doi: 10.1128/mcb.14.5.2958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ng H. C., Singh M., Jeyaseelan K. Identification of two protein serine/threonine kinase genes and molecular cloning of a SNF1 type protein kinase gene from Toxoplasma gondii. Biochem Mol Biol Int. 1995 Jan;35(1):155–165. [PubMed] [Google Scholar]
  24. Petter R., Kwon-Chung K. J. Disruption of the SNF1 gene abolishes trehalose utilization in the pathogenic yeast Candida glabrata. Infect Immun. 1996 Dec;64(12):5269–5273. doi: 10.1128/iai.64.12.5269-5273.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5. [DOI] [PubMed] [Google Scholar]
  26. Rustchenko-Bulgac E. P., Sherman F., Hicks J. B. Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans. J Bacteriol. 1990 Mar;172(3):1276–1283. doi: 10.1128/jb.172.3.1276-1283.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saporito-Irwin S. M., Birse C. E., Sypherd P. S., Fonzi W. A. PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. Mol Cell Biol. 1995 Feb;15(2):601–613. doi: 10.1128/mcb.15.2.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shah H. C., Carlson G. P. Alteration by phenobarbital and 3-methyl-cholanthrene of functional and structural changes in rat liver due to carbon tetrachloride inhalation. J Pharmacol Exp Ther. 1975 Apr;193(1):281–292. [PubMed] [Google Scholar]
  29. Simon M., Binder M., Adam G., Hartig A., Ruis H. Control of peroxisome proliferation in Saccharomyces cerevisiae by ADR1, SNF1 (CAT1, CCR1) and SNF4 (CAT3). Yeast. 1992 Apr;8(4):303–309. doi: 10.1002/yea.320080407. [DOI] [PubMed] [Google Scholar]
  30. Slutsky B., Staebell M., Anderson J., Risen L., Pfaller M., Soll D. R. "White-opaque transition": a second high-frequency switching system in Candida albicans. J Bacteriol. 1987 Jan;169(1):189–197. doi: 10.1128/jb.169.1.189-197.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson-Jaeger S., François J., Gaughran J. P., Tatchell K. Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. Genetics. 1991 Nov;129(3):697–706. doi: 10.1093/genetics/129.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tu J., Carlson M. REG1 binds to protein phosphatase type 1 and regulates glucose repression in Saccharomyces cerevisiae. EMBO J. 1995 Dec 1;14(23):5939–5946. doi: 10.1002/j.1460-2075.1995.tb00282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tung K. S., Hopper A. K. The glucose repression and RAS-cAMP signal transduction pathways of Saccharomyces cerevisiae each affect RNA processing and the synthesis of a reporter protein. Mol Gen Genet. 1995 Apr 10;247(1):48–54. doi: 10.1007/BF00425820. [DOI] [PubMed] [Google Scholar]
  34. Varma A., Edman J. C., Kwon-Chung K. J. Molecular and genetic analysis of URA5 transformants of Cryptococcus neoformans. Infect Immun. 1992 Mar;60(3):1101–1108. doi: 10.1128/iai.60.3.1101-1108.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wickes B. L., Golin J. E., Kwon-Chung K. J. Chromosomal rearrangement in Candida stellatoidea results in a positive effect on phenotype. Infect Immun. 1991 May;59(5):1762–1771. doi: 10.1128/iai.59.5.1762-1771.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wickes B., Staudinger J., Magee B. B., Kwon-Chung K. J., Magee P. T., Scherer S. Physical and genetic mapping of Candida albicans: several genes previously assigned to chromosome 1 map to chromosome R, the rDNA-containing linkage group. Infect Immun. 1991 Jul;59(7):2480–2484. doi: 10.1128/iai.59.7.2480-2484.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yang X., Jiang R., Carlson M. A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex. EMBO J. 1994 Dec 15;13(24):5878–5886. doi: 10.1002/j.1460-2075.1994.tb06933.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES