Hyphal Growth and Virulence in Candida albicans

  • Andrea Walther
  • Jürgen Wendland
Part of the The Mycota book series (MYCOTA, volume 6)

Fungi grow either as unicellular yeasts or form elongated tubes known as hyphae that, by branching, can form large mycelia. Yeast-like growth, as seen, e.g. in the unicellular brewer’s and baker’s yeast Saccharomyces cerevisiae, includes an active step of cell separation after mitosis. Such a cytokinesis requires a partial degradation of the cell wall and the chitin-rich septum at the mother daughter cell junction to allow separation of both cells. In contrast, hyphae consist of multiple concatenated cells which are compartmentalized by septation but which are not fragmented. Dimorphic fungi, such as the human pathogen Candida albicans can switch growth modes between yeast and hyphal stages. This versatility allows conquering different environmental or host niches and in C. albicans contributes to the successful colonization and infection of its host. The pathogenicity of C. albicans is brought about in concert with other virulence factors such as the production of secreted aspartic proteases and lipases or the phase-specific expression of genes, as well as the reduced ability of the host to fight off infections due to a compromised immune system. In this chapter we discuss differences on the molecular level between yeast and hyphal growth by comparison of C. albicans with S. cerevisiae. From there we review the signals that induce filamentation in C. albicans, the signal transduction cascades used to process these signals, and the output in terms of changes at the transcriptional level that induce phase-specific gene expression.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allen AM, King RD (1978) Occlusion, carbon dioxide, and fungal skin infections. Lancet 1:360–362PubMedCrossRefGoogle Scholar
  2. Almirante B, Rodriguez D, Park BJ, Cuenca-Estrella M, Planes AM, Almela M, Mensa J, Sanchez F, Ayats J, Gimenez M, Saballs P, Fridkin SK, Morgan J, Rodriguez-Tudela JL, Warnock DW, Pahissa A (2005) Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43:1829–1835PubMedCrossRefGoogle Scholar
  3. Amoroso G, Morell-Avrahov L, Muller D, Klug K, Sultemeyer D (2005) The gene NCE103 (YNL036w) from Saccharomyces cerevisiae encodes a functional carbonic anhydrase and its transcription is regulated by the concentration of inorganic carbon in the medium. Mol Microbiol 56:549–558PubMedCrossRefGoogle Scholar
  4. Avila-Aguero ML, Canas-Coto A, Ulloa-Gutierrez R, Caro MA, Alfaro B, Paris MM (2005) Risk factors for Candida infections in a neonatal intensive care unit in Costa Rica. Int J Infect Dis 9:90–95PubMedCrossRefGoogle Scholar
  5. Bahn YS, Mühlschlegel FA (2006) CO2 sensing in fungi and beyond. Curr Opin Microbiol 9:572–578PubMedCrossRefGoogle Scholar
  6. Bahn YS, Cox GM, Perfect JR, Heitman J (2005) Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr Biol 15:2013–2020PubMedCrossRefGoogle Scholar
  7. Bassilana M, Blyth J, Arkowitz RA (2003) Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans. Eukaryot Cell 2:9–18PubMedCrossRefGoogle Scholar
  8. Ben-Abraham R, Keller N, Teodorovitch N, Barzilai A, Harel R, Barzilay Z, Paret G (2004) Predictors of adverse outcome from candidal infection in a tertiary care hospital. J Infect 49:317–323PubMedCrossRefGoogle Scholar
  9. Blank ME, Ehmke H (2003) Aquaporin-1 and HCO3(-)-Cl- transporter-mediated transport of CO2 across the human erythrocyte membrane. J Physiol 550:419–429PubMedCrossRefGoogle Scholar
  10. Bockmühl DP, Krishnamurthy S, Gerads M, Sonneborn A, Ernst JF (2001) Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans. Mol Microbiol 42:1243–1257PubMedCrossRefGoogle Scholar
  11. Bose I, Reese AJ, Ory JJ, Janbon G, Doering TL (2003) A yeast under cover: the capsule of Cryptococcus neoformans. Eukaryot Cell 2:655–663PubMedCrossRefGoogle Scholar
  12. Brown AJ, Gow NA (1999) Regulatory networks controlling Candida albicans morphogenesis. Trends Microbiol 7:333–338PubMedCrossRefGoogle Scholar
  13. Calderone RA (2002) Candida and candidiasis. ASM Press, Washington, D.CGoogle Scholar
  14. Calderone RA, Fonzi WA (2001) Virulence factors of Candida albicans. Trends Microbiol 9:327–335PubMedCrossRefGoogle Scholar
  15. Cann MJ, Hammer A, Zhou J, Kanacher T (2003) A defined subset of adenylyl cyclases is regulated by bicarbonate ion. J Biol Chem 278:35033–35038PubMedCrossRefGoogle Scholar
  16. Cao F, Lane S, Raniga PP, Lu Y, Zhou Z, Ramon K, Chen J, Liu H (2006) The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell 17:295–307PubMedCrossRefGoogle Scholar
  17. Carbrey JM, Cormack BP, Agre P (2001) Aquaporin in Candida: characterization of a functional water channel protein. Yeast 18:1391–1396PubMedCrossRefGoogle Scholar
  18. Cassola A, Parrot M, Silberstein S, Magee BB, Passeron S, Giasson L, Cantore ML (2004) Candida albicans lacking the gene encoding the regulatory subunit of protein kinase A displays a defect in hyphal formation and an altered localization of the catalytic subunit. Eukaryot Cell 3:190–199PubMedCrossRefGoogle Scholar
  19. Chen J, Chen J, Lane S, Liu H (2002) A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol Microbiol 46:1335–1344PubMedCrossRefGoogle Scholar
  20. Chen Y, Cann MJ, Litvin TN, Iourgenko V, Sinclair ML, Levin LR, Buck J (2000) Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289:625–628PubMedCrossRefGoogle Scholar
  21. Csank C, Schroppel K, Leberer E, Harcus D, Mohamed O, Meloche S, Thomas DY, Whiteway M (1998) Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun 66:2713–2721PubMedGoogle Scholar
  22. Dai Z, Sirard JC, Mock M, Koehler TM (1995) The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence. Mol Microbiol 16:1171–1181PubMedCrossRefGoogle Scholar
  23. De Bernardis F, Mühlschlegel FA, Cassone A, Fonzi WA (1998) The pH of the host niche controls gene expression in and virulence of Candida albicans. Infect Immun 66:3317–3325PubMedGoogle Scholar
  24. Dekker T, Geier M, Carde RT (2005) Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours. J Exp Biol 208:2963–2972PubMedCrossRefGoogle Scholar
  25. Drysdale M, Bourgogne A, Koehler TM (2005) Transcriptional analysis of the Bacillus anthracis capsule regulators. J Bacteriol 187:5108–5114PubMedCrossRefGoogle Scholar
  26. Eckert SE, Sheth CC, Mühlschlegel (2007) Regulation of morphogenesis in Candida species. In: Hube B, d’Enfert C (eds) Candida: comparative and fungal genomics. Caister Academic Press, London, pp 263–293Google Scholar
  27. El Barkani A, Kurzai O, Fonzi WA, Ramon A, Porta A, Frosch M, Mühlschlegel FA (2000) Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans. Mol Cell Biol 20:4635–4647PubMedCrossRefGoogle Scholar
  28. Endeward V, Musa-Aziz R, Cooper GJ, Chen LM, Pelletier MF, Virkki LV, Supuran CT, King LS, Boron WF, Gros G (2006) Evidence that aquaporin 1 is a major pathway for CO2 transport across the human erythrocyte membrane. Faseb J 20:1974–1981PubMedCrossRefGoogle Scholar
  29. Fang HM, Wang Y (2006) RA domain-mediated interaction of Cyr1 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Mol Microbiol 61:484–496PubMedCrossRefGoogle Scholar
  30. Feng Q, Summers E, Guo B, Fink G (1999) Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol 181:6339–6346PubMedGoogle Scholar
  31. Fonzi WA (1999) PHR1 and PHR2 of Candida albicans encode putative glycosidases required for proper cross-linking of beta-1, 3- and beta-1, 6-glucans. J Bacteriol 181:7070–7079PubMedGoogle Scholar
  32. Frame GW, Strauss WG, Maibach HI (1972) Carbon dioxide emission of the human arm and hand. J Invest Dermatol 59:155–159PubMedCrossRefGoogle Scholar
  33. Fridkin SK, Kaufman D, Edwards JR, Shetty S, Horan T (2006) Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995–2004. Pediatrics 117:1680–1687PubMedCrossRefGoogle Scholar
  34. Guhad FA, Jensen HE, Aalbaek B, Csank C, Mohamed O, Harcus D, Thomas DY, Whiteway M, Hau J (1998) Mitogen-activated protein kinase-defective Candida albicans is avirulent in a novel model of localized murine candidiasis. FEMS Microbiol Lett 166:135–139PubMedCrossRefGoogle Scholar
  35. Guignot J, Mock M, Fouet A (1997) AtxA activates the transcription of genes harbored by both Bacillus anthracis virulence plasmids. FEMS Microbiol Lett 147:203–207PubMedCrossRefGoogle Scholar
  36. Hammer A, Hodgson DR, Cann MJ (2006) Regulation of prokaryotic adenylyl cyclases by CO2. Biochem J 396: 215–218PubMedCrossRefGoogle Scholar
  37. Hanoune J, Defer N (2001) Regulation and role of adenylyl cyclase isoforms. Annu Rev Pharmacol Toxicol 41:145–174PubMedCrossRefGoogle Scholar
  38. Hewett-Emmett D (2000) Evolution and distribution of the carbonic anhydrase gene families. In: Chegwidden WR, Carter ND, Edwards YH (eds) The carbonic anhydrases: new horizons. Birkhäuser, Basel, pp 29–76Google Scholar
  39. Jaiswal BS, Conti M (2003) Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa. Proc Natl Acad Sci USA 100:10676–10681PubMedCrossRefGoogle Scholar
  40. Javelle A, Morel M, Rodriguez-Pastrana BR, Botton B, Andre B, Marini AM, Brun A, Chalot M (2003) Molecular characterization, function and regulation of ammonium transporters (Amt) and ammonium-metabolizing enzymes (GS, NADP-GDH) in the ectomycorrhizal fungus Hebeloma cylindrosporum. Mol Microbiol 47:411–430PubMedCrossRefGoogle Scholar
  41. Kamenetsky M, Middelhaufe S, Bank EM, Levin LR, Buck J, Steegborn C (2006) Molecular details of cAMP generation in Mammalian cells: a tale of two systems. J Mol Biol 362:623–639PubMedCrossRefGoogle Scholar
  42. Kibbler CC, Seaton S, Barnes RA, Gransden WR, Holliman RE, Johnson EM, Perry JD, Sullivan DJ, Wilson JA (2003) Management and outcome of bloodstream infections due to Candida species in England and Wales. J Hosp Infect 54:18–24PubMedCrossRefGoogle Scholar
  43. Klengel T, Liang WJ, Chaloupka J, Ruoff C, Schroppel K, Naglik JR, Eckert SE, Mogensen EG, Haynes K, Tuite MF, Levin LR, Buck J, Mühlschlegel FA (2005) Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr Biol 15:2021–2026PubMedCrossRefGoogle Scholar
  44. Kohler JR, Fink GR (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 USA 93:13223–13228PubMedCrossRefGoogle Scholar
  45. Kustu S, Inwood W (2006) Biological gas channels for NH3 and CO2: evidence that Rh (Rhesus) proteins are CO2 channels. Transfus Clin Biol 13:103–110PubMedCrossRefGoogle Scholar
  46. Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schroppel K (2001) Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans. Mol Microbiol 42:673–687PubMedCrossRefGoogle Scholar
  47. Lengeler KB, Davidson RC, D’Souza C, Harashima T, Shen WC, Wang P, Pan X, Waugh M, Heitman J (2000) Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64:746–785PubMedCrossRefGoogle Scholar
  48. Lindskog S (1997) Structure and mechanism of carbonic anhydrase. Pharmacol Ther 74:1–20PubMedCrossRefGoogle Scholar
  49. Litvin TN, Kamenetsky M, Zarifyan A, Buck J, Levin LR (2003) Kinetic properties of “soluble” adenylyl cyclase. Synergism between calcium and bicarbonate. J Biol Chem 278:15922–15926PubMedCrossRefGoogle Scholar
  50. Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90:939–949PubMedCrossRefGoogle Scholar
  51. McIver KS, Heath AS, Scott JR (1995) Regulation of virulence by environmental signals in group A streptococci: influence of osmolarity, temperature, gas exchange, and iron limitation on emm transcription. Infect Immun 63:4540–4542PubMedGoogle Scholar
  52. MacPhail GL, Taylor GD, Buchanan-Chell M, Ross C, Wilson S, Kureishi A (2002) Epidemiology, treatment and outcome of candidemia: a five-year review at three Canadian hospitals. Mycoses 45:141–145PubMedCrossRefGoogle Scholar
  53. Magee BB, Legrand M, Alarco AM, Raymond M, Magee PT (2002) Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol Microbiol 46:1345–1351PubMedCrossRefGoogle Scholar
  54. Marini AM, Boeckstaens M, Andre B (2006) From yeast ammonium transporters to Rhesus proteins, isolation and functional characterization. Transfus Clin Biol 13:95–96PubMedCrossRefGoogle Scholar
  55. Martin D, Persat F, Piens MA, Picot S (2005) Candida species distribution in bloodstream cultures in Lyon, France, 1998–2001. Eur J Clin Microbiol Infect Dis 24:329–333PubMedCrossRefGoogle Scholar
  56. Mogensen EG, Janbon G, Chaloupka J, Steegborn C, Fu MS, Moyrand F, Klengel T, Pearson DS, Geeves MA, Buck J, Levin LR, Mühlschlegel FA (2006) Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1. Eukaryot Cell 5:103–111PubMedCrossRefGoogle Scholar
  57. Monge RA, Roman E, Nombela C, Pla J (2006) The MAP kinase signal transduction network in Candida albicans. Microbiology 152:905–912PubMedCrossRefGoogle Scholar
  58. Mühlschlegel FA, Fonzi WA (1997) PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression. Mol Cell Biol 17:5960–5967PubMedGoogle Scholar
  59. Okada N, Geist RT, Caparon MG (1993) Positive transcriptional control of mry regulates virulence in the group A streptococcus. Mol Microbiol 7:893–903PubMedCrossRefGoogle Scholar
  60. Odds FC (1988) Candida and Candidosis. Balliere Tindall, LondonGoogle Scholar
  61. Park H, Myers CL, Sheppard DC, Phan QT, Sanchez AA, Edwards JE Jr, Filler SG (2005) Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell Microbiol 7:499–510PubMedCrossRefGoogle Scholar
  62. Perfect JR, Casadevall A (2002) Cryptococcosis. Infect Dis Clin North Am 16:837–874, v–viPubMedCrossRefGoogle Scholar
  63. Phan QT, Belanger PH, Filler SG (2000) Role of hyphal formation in interactions of Candida albicans with endothelial cells. Infect Immun 68:3485–3490PubMedCrossRefGoogle Scholar
  64. Phillips AJ, Crowe JD, Ramsdale M (2006) Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans. Proc Natl Acad Sci USA 103:726–731PubMedCrossRefGoogle Scholar
  65. Rangel-Frausto MS, Wiblin T, Blumberg HM, Saiman L, Patterson J, Rinaldi M, Pfaller M, Edwards JE Jr, Jarvis W, Dawson J, Wenzel RP (1999) National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis 29:253–258PubMedCrossRefGoogle Scholar
  66. Richter SS, Galask RP, Messer SA, Hollis RJ, Diekema DJ, Pfaller MA (2005) Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol 43:2155–2162PubMedCrossRefGoogle Scholar
  67. Rocha CR, Schroppel K, Harcus D, Marcil A, Dignard D, Taylor BN, Thomas DY, 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 12:3631–3643PubMedGoogle Scholar
  68. Sanglard D, Odds FC (2002) Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2:73–85PubMedCrossRefGoogle Scholar
  69. Saporito-Irwin SM, Birse CE, Sypherd PS, Fonzi WA (1995) PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. Mol Cell Biol 15:601–613PubMedGoogle Scholar
  70. Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL (2003) Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell 2:1053–1060PubMedCrossRefGoogle Scholar
  71. Sheth CC, Johnson E, Baker ME, Haynes K, Mühlschlegel FA (2005) Phenotypic identification of Candida albicans by growth on chocolate agar. Med Mycol 43:735–738PubMedCrossRefGoogle Scholar
  72. Sheth CC, Mogensen EG, Fu MS, Blomfield IC, Muhlschlegel FA (2008) Candida albicans HSP12 is co-regulated by Physiological CO2 and pH. Fungal Genet Biol In Press Google Scholar
  73. Sims W (1986) Effect of carbon dioxide on the growth and form of Candida albicans. J Med Microbiol 22:203–208PubMedCrossRefGoogle Scholar
  74. Smith KS, Ferry JG (2000) Prokaryotic carbonic anhydrases. FEMS Microbiol Rev 24:335–366PubMedCrossRefGoogle Scholar
  75. Sonneborn A, Bockmühl DP, Gerads M, Kurpanek K, Sanglard D, Ernst, JF (2000) Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol 35:386–396PubMedCrossRefGoogle Scholar
  76. Soupene E, Inwood W, Kustu S (2004) Lack of the Rhesus protein Rh1 impairs growth of the green alga Chlamydomonas reinhardtii at high CO2. Proc Natl Acad Sci USA 101:7787–7792PubMedCrossRefGoogle Scholar
  77. Souto G, Giacometti R, Silberstein S, Giasson L, Cantore ML, Passeron S (2006) Expression of TPK1 and TPK2 genes encoding PKA catalytic subunits during growth and morphogenesis in Candida albicans. Yeast 23: 591–603PubMedCrossRefGoogle Scholar
  78. Steegborn C, Litvin TN, Levin LR, Buck J, Wu H (2005) Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment. Nat Struct Mol Biol 12:32–37PubMedCrossRefGoogle Scholar
  79. Stoldt VR, Sonneborn A, Leuker CE, Ernst JF (1997) Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. Embo J 16:1982–1991PubMedCrossRefGoogle Scholar
  80. Suh GS, Wong AM, Hergarden AC, Wang JW, Simon AF, Benzer S, Axel R, Anderson DJ (2004) A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila. Nature 431: 854–859PubMedCrossRefGoogle Scholar
  81. Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibbler CC, Faure O, Biraghi E, Canton E, Zimmermann K, Seaton S, Grillot R (2004) Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23:317–322PubMedCrossRefGoogle Scholar
  82. Tripp BC, Smith K, Ferry JG (2001) Carbonic anhydrase: new insights for an ancient enzyme. J Biol Chem 276:48615–48618PubMedCrossRefGoogle Scholar
  83. Tripp BC, Bell CB 3rd, Cruz F, Krebs C, Ferry JG (2004) A role for iron in an ancient carbonic anhydrase. J Biol Chem 279:6683–6687PubMedCrossRefGoogle Scholar
  84. Tyerman SD, Niemietz CM, Bramley H (2002) Plant aquaporins: multifunctional water and solute channels with expanding roles. Plant Cell Environ 25:173–194PubMedCrossRefGoogle Scholar
  85. Uchida I, Makino S, Sekizaki T, Terakado N (1997) Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis. Mol Microbiol 23:1229–1240PubMedCrossRefGoogle Scholar
  86. Uehlein N, Lovisolo C, Siefritz F, Kaldenhoff R (2003) The tobacco aquaporin NtAQP1 is a membrane CO2 pore with physiological functions. Nature 425:734–737PubMedCrossRefGoogle Scholar
  87. Ushinsky SC, Harcus D, Ash J, Dignard D, Marcil A, Morchhauser J, Thomas DY, Whiteway M, Leberer E (2002) CDC42 is required for polarized growth in human pathogen Candida albicans. Eukaryot Cell 1:95–104PubMedCrossRefGoogle Scholar
  88. Vandenberg AL, Ibrahim AS, Edwards JE Jr, Toenjes KA, Johnson DI (2004) Cdc42p GTPase regulates the budded-to-hyphal-form transition and expression of hypha-specific transcripts in Candida albicans. Eukaryot Cell 3:724–734PubMedCrossRefGoogle Scholar
  89. Wuttke MS, Buck J, Levin LR (2001) Bicarbonate-regulated soluble adenylyl cyclase. J Pancreas 2:154–158Google Scholar
  90. Zippin JH, Levin LR, Buck J (2001) CO(2)/HCO(3)(-)-responsive soluble adenylyl cyclase as a putative metabolic sensor. Trends Endocrinol Metab 12:366–370PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Andrea Walther
    • 1
  • Jürgen Wendland
    • 1
  1. 1.Yeast BiologyCarlsberg LaboratoryValby, CopenhagenDenmark

Personalised recommendations