Try out PMC Labs and tell us what you think. Learn More.

Logo of jbacterLink to Publisher's site
J Bacteriol. 1996 Sep; 178(18): 5353–5360.
PMCID: PMC178351
PMID: 8808922

The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins.


A hyphally regulated gene (HYR1) from the dimorphic human pathogenic fungus Candida albicans was isolated and characterized. Northern (RNA) analyses showed that the HYR1 mRNA was induced specifically in response to hyphal development when morphogenesis was stimulated by serum addition and temperature elevation, increases in both culture pH and temperature, or N-acetylglucosamine addition. The HYR1 gene sequence revealed a 937-codon open reading frame capable of encoding a protein with an N-terminal signal sequence, a C-terminal glycosylphosphatidylinositol-anchoring domain, 17 potential N glycosylation sites, and a large domain rich in serine and threonine (51% of 230 residues). These features are observed in many yeast cell wall proteins, but no homologs are present in the databases. In addition, Hyr1p contained a second domain rich in glycine, serine, and asparagine (79% of 239 residues). The HYR1 locus in C. albicans CAI4 was disrupted by "Ura-blasting," but the resulting homozygous delta hyr1/delta hyr1 null mutant displayed no obvious morphological phenotype. The growth rates for yeast cells and hyphae and the kinetics of germ tube formation in the null mutant were unaffected. Aberrant expression of HYR1 in yeast cells, when an ADH1-HYR1 fusion was used, did not stimulate hyphal formation in C. albicans or pseudohyphal growth in Saccharomyces cerevisiae. HYR1 appears to encode a nonessential component of the hyphal cell wall.

Full Text

The Full Text of this article is available as a PDF (752K).

Selected References

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

  • Alani E, Cao L, Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. [PMC free article] [PubMed] [Google Scholar]
  • Barki M, Koltin Y, Yanko M, Tamarkin A, Rosenberg M. Isolation of a Candida albicans DNA sequence conferring adhesion and aggregation on Saccharomyces cerevisiae. J Bacteriol. 1993 Sep;175(17):5683–5689. [PMC free article] [PubMed] [Google Scholar]
  • Bertram G, Swoboda RK, Gooday GW, Gow NA, Brown AJ. Structure and regulation of the Candida albicans ADH1 gene encoding an immunogenic alcohol dehydrogenase. Yeast. 1996 Feb;12(2):115–127. [PubMed] [Google Scholar]
  • Birse CE, Irwin MY, Fonzi WA, Sypherd PS. Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infect Immun. 1993 Sep;61(9):3648–3655. [PMC free article] [PubMed] [Google Scholar]
  • Buffo J, Herman MA, Soll DR. A characterization of pH-regulated dimorphism in Candida albicans. Mycopathologia. 1984 Mar 15;85(1-2):21–30. [PubMed] [Google Scholar]
  • Calderone RA. Recognition between Candida albicans and host cells. Trends Microbiol. 1993 May;1(2):55–58. [PubMed] [Google Scholar]
  • Calderone RA, Braun PC. Adherence and receptor relationships of Candida albicans. Microbiol Rev. 1991 Mar;55(1):1–20. [PMC free article] [PubMed] [Google Scholar]
  • Casanova M, Lopez-Ribot JL, Martinez JP, Sentandreu R. Characterization of cell wall proteins from yeast and mycelial cells of Candida albicans by labelling with biotin: comparison with other techniques. Infect Immun. 1992 Nov;60(11):4898–4906. [PMC free article] [PubMed] [Google Scholar]
  • Chen-Wu JL, Zwicker J, Bowen AR, Robbins PW. Expression of chitin synthase genes during yeast and hyphal growth phases of Candida albicans. Mol Microbiol. 1992 Feb;6(4):497–502. [PubMed] [Google Scholar]
  • Clark KL, Feldmann PJ, Dignard D, Larocque R, Brown AJ, Lee MG, Thomas DY, Whiteway M. Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans. Mol Gen Genet. 1995 Dec 20;249(6):609–621. [PubMed] [Google Scholar]
  • Cutler JE. Putative virulence factors of Candida albicans. Annu Rev Microbiol. 1991;45:187–218. [PubMed] [Google Scholar]
  • Delbrück S, Ernst JF. Morphogenesis-independent regulation of actin transcript levels in the pathogenic yeast Candida albicans. Mol Microbiol. 1993 Nov;10(4):859–866. [PubMed] [Google Scholar]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed] [Google Scholar]
  • Elorza MV, Murgui A, Sentandreu R. Dimorphism in Candida albicans: contribution of mannoproteins to the architecture of yeast and mycelial cell walls. J Gen Microbiol. 1985 Sep;131(9):2209–2216. [PubMed] [Google Scholar]
  • Elorza MV, Marcilla A, Sentandreu R. Wall mannoproteins of the yeast and mycelial cells of Candida albicans: nature of the glycosidic bonds and polydispersity of their mannan moieties. J Gen Microbiol. 1988 Aug;134(8):2393–2403. [PubMed] [Google Scholar]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed] [Google Scholar]
  • Ferguson MA, Williams AF. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. [PubMed] [Google Scholar]
  • Finney R, Langtimm CJ, Soll DR. The programs of protein synthesis accompanying the establishment of alternative phenotypes in Candida albicans. Mycopathologia. 1985 Jul;91(1):3–15. [PubMed] [Google Scholar]
  • Fonzi WA, Irwin MY. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. [PMC free article] [PubMed] [Google Scholar]
  • Ghannoum MA, Spellberg B, Saporito-Irwin SM, Fonzi WA. Reduced virulence of Candida albicans PHR1 mutants. Infect Immun. 1995 Nov;63(11):4528–4530. [PMC free article] [PubMed] [Google Scholar]
  • Gimeno CJ, Ljungdahl PO, Styles CA, Fink GR. 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. [PubMed] [Google Scholar]
  • Gow NA, Robbins PW, Lester JW, Brown AJ, Fonzi WA, Chapman T, Kinsman OS. 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. [PMC free article] [PubMed] [Google Scholar]
  • Hoffman CS, Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. [PubMed] [Google Scholar]
  • Hoyer LL, Scherer S, Shatzman AR, Livi GP. Candida albicans ALS1: domains related to a Saccharomyces cerevisiae sexual agglutinin separated by a repeating motif. Mol Microbiol. 1995 Jan;15(1):39–54. [PubMed] [Google Scholar]
  • Hube B, Monod M, Schofield DA, Brown AJ, Gow NA. Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol. 1994 Oct;14(1):87–99. [PubMed] [Google Scholar]
  • 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. [PMC free article] [PubMed] [Google Scholar]
  • Kapteyn JC, Montijn RC, Dijkgraaf GJ, Klis FM. Identification of beta-1,6-glucosylated cell wall proteins in yeast and hyphal forms of Candida albicans. Eur J Cell Biol. 1994 Dec;65(2):402–407. [PubMed] [Google Scholar]
  • Klis FM. Review: cell wall assembly in yeast. Yeast. 1994 Jul;10(7):851–869. [PubMed] [Google Scholar]
  • Kurtz MB, Cortelyou MW, Kirsch DR. Integrative transformation of Candida albicans, using a cloned Candida ADE2 gene. Mol Cell Biol. 1986 Jan;6(1):142–149. [PMC free article] [PubMed] [Google Scholar]
  • Lee KL, Buckley HR, Campbell CC. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans. Sabouraudia. 1975 Jul;13(2):148–153. [PubMed] [Google Scholar]
  • Lillehaug JR, Kleppe K. Effect of salts and polyamines on T4 polynucleotide kinase. Biochemistry. 1975 Mar 25;14(6):1225–1229. [PubMed] [Google Scholar]
  • Lindquist S. Regulation of protein synthesis during heat shock. Nature. 1981 Sep 24;293(5830):311–314. [PubMed] [Google Scholar]
  • Lipke PN, Wojciechowicz D, Kurjan J. AG alpha 1 is the structural gene for the Saccharomyces cerevisiae alpha-agglutinin, a cell surface glycoprotein involved in cell-cell interactions during mating. Mol Cell Biol. 1989 Aug;9(8):3155–3165. [PMC free article] [PubMed] [Google Scholar]
  • Lopez-Ribot JL, Casanova M, Martinez JP, Sentandreu R. Characterization of cell wall proteins of yeast and hydrophobic mycelial cells of Candida albicans. Infect Immun. 1991 Jul;59(7):2324–2332. [PMC free article] [PubMed] [Google Scholar]
  • Martin MV, Craig GT, Lamb DJ. An investigation of the role of true hypha production in the pathogenesis of experimental oral candidosis. Sabouraudia. 1984;22(6):471–476. [PubMed] [Google Scholar]
  • Matthews RC. Pathogenicity determinants of Candida albicans: potential targets for immunotherapy? Microbiology. 1994 Jul;140(Pt 7):1505–1511. [PubMed] [Google Scholar]
  • Mattia E, Carruba G, Angiolella L, Cassone A. Induction of germ tube formation by N-acetyl-D-glucosamine in Candida albicans: uptake of inducer and germinative response. J Bacteriol. 1982 Nov;152(2):555–562. [PMC free article] [PubMed] [Google Scholar]
  • Moore PA, Sagliocco FA, Wood RM, Brown AJ. Yeast glycolytic mRNAs are differentially regulated. Mol Cell Biol. 1991 Oct;11(10):5330–5337. [PMC free article] [PubMed] [Google Scholar]
  • Nuoffer C, Jenö P, Conzelmann A, Riezman H. Determinants for glycophospholipid anchoring of the Saccharomyces cerevisiae GAS1 protein to the plasma membrane. Mol Cell Biol. 1991 Jan;11(1):27–37. [PMC free article] [PubMed] [Google Scholar]
  • Popolo L, Vai M, Gatti E, Porello S, Bonfante P, Balestrini R, Alberghina L. Physiological analysis of mutants indicates involvement of the Saccharomyces cerevisiae GPI-anchored protein gp115 in morphogenesis and cell separation. J Bacteriol. 1993 Apr;175(7):1879–1885. [PMC free article] [PubMed] [Google Scholar]
  • Roy A, Lu CF, Marykwas DL, Lipke PN, Kurjan J. The AGA1 product is involved in cell surface attachment of the Saccharomyces cerevisiae cell adhesion glycoprotein a-agglutinin. Mol Cell Biol. 1991 Aug;11(8):4196–4206. [PMC free article] [PubMed] [Google Scholar]
  • Ryley JF, Ryley NG. Candida albicans--do mycelia matter? J Med Vet Mycol. 1990;28(3):225–239. [PubMed] [Google Scholar]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed] [Google Scholar]
  • Santiago TC, Purvis IJ, Bettany AJ, Brown AJ. The relationship between mRNA stability and length in Saccharomyces cerevisiae. Nucleic Acids Res. 1986 Nov 11;14(21):8347–8360. [PMC free article] [PubMed] [Google Scholar]
  • Santos MA, Keith G, Tuite MF. Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon. EMBO J. 1993 Feb;12(2):607–616. [PMC free article] [PubMed] [Google Scholar]
  • Santos MA, Tuite MF. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res. 1995 May 11;23(9):1481–1486. [PMC free article] [PubMed] [Google Scholar]
  • Saporito-Irwin SM, Birse CE, Sypherd PS, Fonzi WA. PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. Mol Cell Biol. 1995 Feb;15(2):601–613. [PMC free article] [PubMed] [Google Scholar]
  • Scherer S, Magee PT. Genetics of Candida albicans. Microbiol Rev. 1990 Sep;54(3):226–241. [PMC free article] [PubMed] [Google Scholar]
  • Schreuder MP, Brekelmans S, van den Ende H, Klis FM. Targeting of a heterologous protein to the cell wall of Saccharomyces cerevisiae. Yeast. 1993 Apr;9(4):399–409. [PubMed] [Google Scholar]
  • Sherwood J, Gow NA, Gooday GW, Gregory DW, Marshall D. Contact sensing in Candida albicans: a possible aid to epithelial penetration. J Med Vet Mycol. 1992;30(6):461–469. [PubMed] [Google Scholar]
  • Smith DJ, Cooper M, DeTiani M, Losberger C, Payton MA. The Candida albicans PMM1 gene encoding phosphomannomutase complements a Saccharomyces cerevisiae sec 53-6 mutation. Curr Genet. 1992 Dec;22(6):501–503. [PubMed] [Google Scholar]
  • Smith RJ, Milewski S, Brown AJ, Gooday GW. Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6-phosphate amidotransferase of Candida albicans. J Bacteriol. 1996 Apr;178(8):2320–2327. [PMC free article] [PubMed] [Google Scholar]
  • Sobel JD, Muller G, Buckley HR. Critical role of germ tube formation in the pathogenesis of candidal vaginitis. Infect Immun. 1984 Jun;44(3):576–580. [PMC free article] [PubMed] [Google Scholar]
  • Soll DR. The regulation of cellular differentiation in the dimorphic yeast Candida albicans. Bioessays. 1986 Jul;5(1):5–11. [PubMed] [Google Scholar]
  • Srikantha T, Klapach A, Lorenz WW, Tsai LK, Laughlin LA, Gorman JA, Soll DR. The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent reporter for differential gene expression in Candida albicans. J Bacteriol. 1996 Jan;178(1):121–129. [PMC free article] [PubMed] [Google Scholar]
  • Staab JF, Ferrer CA, Sundstrom P. Developmental expression of a tandemly repeated, proline-and glutamine-rich amino acid motif on hyphal surfaces on Candida albicans. J Biol Chem. 1996 Mar 15;271(11):6298–6305. [PubMed] [Google Scholar]
  • Sundstrom PM, Tam MR, Nichols EJ, Kenny GE. Antigenic differences in the surface mannoproteins of Candida albicans as revealed by monoclonal antibodies. Infect Immun. 1988 Mar;56(3):601–606. [PMC free article] [PubMed] [Google Scholar]
  • Swoboda RK, Bertram G, Budge S, Gooday GW, Gow NA, Brown AJ. Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans. Infect Immun. 1995 Nov;63(11):4506–4514. [PMC free article] [PubMed] [Google Scholar]
  • Swoboda RK, Bertram G, Colthurst DR, Tuite MF, Gow NA, Gooday GW, Brown AJ. Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans. Microbiology. 1994 Oct;140(Pt 10):2611–2616. [PubMed] [Google Scholar]
  • Swoboda RK, Bertram G, Delbrück S, Ernst JF, Gow NA, Gooday GW, Brown AJ. Fluctuations in glycolytic mRNA levels during morphogenesis in Candida albicans reflect underlying changes in growth and are not a response to cellular dimorphism. Mol Microbiol. 1994 Aug;13(4):663–672. [PubMed] [Google Scholar]
  • Swoboda RK, Bertram G, Hollander H, Greenspan D, Greenspan JS, Gow NA, Gooday GW, Brown AJ. Glycolytic enzymes of Candida albicans are nonubiquitous immunogens during candidiasis. Infect Immun. 1993 Oct;61(10):4263–4271. [PMC free article] [PubMed] [Google Scholar]
  • Swoboda RK, Broadbent ID, Bertram G, Budge S, Gooday GW, Gow NA, Brown AJ. Structure and regulation of a Candida albicans RP10 gene which encodes an immunogenic protein homologous to Saccharomyces cerevisiae ribosomal protein 10. J Bacteriol. 1995 Mar;177(5):1239–1246. [PMC free article] [PubMed] [Google Scholar]
  • Teunissen AW, Holub E, van der Hucht J, van den Berg JA, Steensma HY. Sequence of the open reading frame of the FLO1 gene from Saccharomyces cerevisiae. Yeast. 1993 Apr;9(4):423–427. [PubMed] [Google Scholar]
  • Thomas BJ, Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. [PubMed] [Google Scholar]
  • Torosantucci A, Boccanera M, Casalinuovo I, Pellegrini G, Cassone A. Differences in the antigenic expression of immunomodulatory mannoprotein constituents on yeast and mycelial forms of Candida albicans. J Gen Microbiol. 1990 Jul;136(7):1421–1428. [PubMed] [Google Scholar]
  • Udenfriend S, Kodukula K. How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu Rev Biochem. 1995;64:563–591. [PubMed] [Google Scholar]
  • Vai M, Gatti E, Lacanà E, Popolo L, Alberghina L. Isolation and deduced amino acid sequence of the gene encoding gp115, a yeast glycophospholipid-anchored protein containing a serine-rich region. J Biol Chem. 1991 Jul 5;266(19):12242–12248. [PubMed] [Google Scholar]
  • Vai M, Popolo L, Grandori R, Lacanà E, Alberghina L. The cell cycle modulated glycoprotein GP115 is one of the major yeast proteins containing glycosylphosphatidylinositol. Biochim Biophys Acta. 1990 May 8;1038(3):277–285. [PubMed] [Google Scholar]
  • van der Vaart JM, Caro LH, Chapman JW, Klis FM, Verrips CT. Identification of three mannoproteins in the cell wall of Saccharomyces cerevisiae. J Bacteriol. 1995 Jun;177(11):3104–3110. [PMC free article] [PubMed] [Google Scholar]
  • White TC, Andrews LE, Maltby D, Agabian N. The "universal" leucine codon CTG in the secreted aspartyl proteinase 1 (SAP1) gene of Candida albicans encodes a serine in vivo. J Bacteriol. 1995 May;177(10):2953–2955. [PMC free article] [PubMed] [Google Scholar]
  • Wojciechowicz D, Lu CF, Kurjan J, Lipke PN. Cell surface anchorage and ligand-binding domains of the Saccharomyces cerevisiae cell adhesion protein alpha-agglutinin, a member of the immunoglobulin superfamily. Mol Cell Biol. 1993 Apr;13(4):2554–2563. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)