Applied Microbiology and Biotechnology

, Volume 78, Issue 1, pp 17–28 | Cite as

A small protein that fights fungi: AFP as a new promising antifungal agent of biotechnological value



As fungal infections are becoming more prevalent in the medical or agricultural fields, novel and more efficient antifungal agents are badly needed. Within the scope of developing new strategies for the management of fungal infections, antifungal compounds that target essential fungal cell wall components are highly preferable. Ideally, newly developed antimycotics should also combine major aspects such as sustainability, high efficacy, limited toxicity and low costs of production. A naturally derived molecule that possesses all the desired characteristics is the antifungal protein (AFP) secreted by the filamentous ascomycete Aspergillus giganteus. AFP is a small, basic and cysteine-rich peptide that exerts extremely potent antifungal activity against human- and plant-pathogenic fungi without affecting the viability of bacteria, yeast, plant and mammalian cells. This review summarises the current knowledge of the structure, mode of action and expression of AFP, and highlights similarities and differences concerning these issues between AFP and its related proteins from other Ascomycetes. Furthermore, the potential use of AFP in the combat against fungal contaminations and infections will be discussed.


Antifungal protein Aspergillus giganteus Pathogenic fungi Cell wall integrity Chitin biosynthesis Antifungal treatment 



The author would like to thank the Arbeitsgemeinschaft industrieller Forschungsvereinigungen “Otto von Guericke” for the financial support, and Silke Hagen and Anja Spielvogel for sharing unpublished data.


  1. Arcus V (2002) OB-fold domains: a snapshot of the evolution of sequence, structure and function. Curr Opin Struct Biol 12:794–801Google Scholar
  2. Bartnicki-García S (2006) Chitosomes: past, present and future. FEMS Yeast Res 6:957–965Google Scholar
  3. Benitez T, Rincon AM, Limon MC, Codon AC (2004) Biocontrol mechanisms of Trichoderma strains. Int Microbiol 7:249–260Google Scholar
  4. Borneman AR, Hynes MJ, Andrianopoulos A (2002) A basic helix–loop–helix protein with similarity to the fungal morphological regulators, Phd1p, Efg1p and StuA, controls conidiation but not dimorphic growth in Penicillium marneffei. Mol Microbiol 44:621–631Google Scholar
  5. Bracker CE, Ruiz-Herrera J, Bartnicki-García S (1976) Structure and transformation of chitin synthetase particles (chitosomes) during microfibril synthesis in vitro. Proc Natl Acad Sci U S A 73:4570–4574Google Scholar
  6. Bussink HJ, Osmani SA (1998) A cyclin-dependent kinase family member (PHOA) is required to link developmental fate to environmental conditions in Aspergillus nidulans. EMBO J 17:3990–4003Google Scholar
  7. Campos-Olivas R, Bruix M, Santoro J, Lacadena J, Martinez del Pozo A, Gavilanes JG, Rico M (1995) NMR solution structure of the antifungal protein from Aspergillus giganteus: evidence for cysteine pairing isomerism. Biochemistry 34:3009–3021Google Scholar
  8. Cappelletty D, Eiselstein-McKitrick K (2007) The echinocandins. Pharmacotherapy 27:369–388Google Scholar
  9. Coca M, Bortolotti C, Rufat M, Peñas G, Eritja R, Tharreau D, del Pozo AM, Messeguer J, San Segundo B (2004) Transgenic rice plants expressing the antifungal AFP protein from Aspergillus giganteus show enhanced resistance to the rice blast fungus Magnaporthe grisea. Plant Mol Biol 54:245–259Google Scholar
  10. Cohen E (2001) Chitin synthesis and inhibition: a revisit. Pest Manag Sci 57:946–950Google Scholar
  11. Cyert MS (2003) Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem Biophys Res Commun 311:1143–1150Google Scholar
  12. Damveld RA, Arentshorst M, Franken A, vanKuyk PA, Klis FM, van den Hondel CA, Ram AF (2005) The Aspergillus niger MADS-box transcription factor RlmA is required for cell wall reinforcement in response to cell wall stress. Mol Microbiol 58:305–319Google Scholar
  13. De Lucca AJ, Walsh TJ (1999) Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob Agents Chemother 43:1–11Google Scholar
  14. Delom F, Szponarski W, Sommerer N, Boyer JC, Bruneau JM, Rossignol M, Gibrat R (2006) The plasma membrane proteome of Saccharomyces cerevisiae and its response to the antifungal calcofluor. Proteomics 6:3029–3039Google Scholar
  15. Dou X, Wu D, An W, Davies J, Hashmi SB, Ukil L, Osmani SA (2003) The PHOA and PHOB cyclin-dependent kinases perform an essential function in Aspergillus nidulans. Genetics 165:1105–1115Google Scholar
  16. Dutton JR, Johns S, Miller BL (1997) StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans. EMBO J 16:5710–5721Google Scholar
  17. Edlind TD, Katiyar SK (2004) The echinocandin “target” identified by cross-linking is a homolog of Pil1 and Lsp1, sphingolipid-dependent regulators of cell wall integrity signaling. Antimicrob Agents Chemother 48:4491Google Scholar
  18. Edwards SG (2004) Influence of agricultural practices on Fusarium infection of cereals and subsequent contamination of grain by trichothecene mycotoxins. Toxicol Lett 153:29–35Google Scholar
  19. Espeso EA, Peñalva MA (1996) Three binding sites for the Aspergillus nidulans PacC zinc-finger transcription factor are necessary and sufficient for regulation by ambient pH of the isopenicillin N synthase gene promoter. J Biol Chem 271:28825–28830Google Scholar
  20. Espeso EA, Tilburn J, Arst HN Jr., Peñalva MA (1993) pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene. EMBO J 12:3947–3956Google Scholar
  21. Ferket KK, Levery SB, Park C, Cammue BP, Thevissen K (2003) Isolation and characterization of Neurospora crassa mutants resistant to antifungal plant defensins. Fungal Genet Biol 40:176–185Google Scholar
  22. Fortwendel JR, Zhao W, Bhabhra R, Park S, Perlin DS, Askew DS, Rhodes JC (2005) A fungus-specific Ras homolog contributes to the hyphal growth and virulence of Aspergillus fumigatus. Eukaryot Cell 4:1982–1989Google Scholar
  23. Futerman AH, Hannun YA (2004) The complex life of simple sphingolipids. EMBO Rep 5:777–782Google Scholar
  24. Galgóczy L, Papp T, Leiter É, Marx F, Pócsi I, Vágvölgyi C (2005) Sensitivity of different zygomycetes to the Penicillium chrysogenum antifungal protein (PAF). J Basic Microbiol 45:136–141Google Scholar
  25. Geisen R (2000) P. nalgiovense carries a gene which is homologous to the paf gene of P. chrysogenum which codes for an antifungal peptide. Int J Food Microbiol 62:95–101Google Scholar
  26. Girgi M, Breese WA, Lörz H, Oldach KH (2006) Rust and downy mildew resistance in pearl millet (Pennisetum glaucum) mediated by heterologous expression of the afp gene from Aspergillus giganteus. Transgenic Res 15:313–324Google Scholar
  27. Gun Lee D, Shin SY, Maeng CY, Jin ZZ, Kim KL, Hahm KS (1999) Isolation and characterization of a novel antifungal peptide from Aspergillus niger. Biochem Biophys Res Commun 263:646–651Google Scholar
  28. Gupte M, Kulkarni P, Ganguli BN (2002) Antifungal antibiotics. Appl Microbiol Biotechnol 58:46–57Google Scholar
  29. Hagen S, Marx F, Ram AF, Meyer V (2007) The antifungal protein AFP from Aspergillus giganteus inhibits chitin synthesis in sensitive fungi. Appl Environ Microbiol 73:2128–2134Google Scholar
  30. Harris SD, Read ND, Roberson RW, Shaw B, Seiler S, Plamann M, Momany M (2005) Polarisome meets Spitzenkörper: Microscopy, genetics, and genomics converge. Eukaryot Cell 4:225–229Google Scholar
  31. Hector RF (2005) An overview of antifungal drugs and their use for treatment of deep and superficial mycoses in animals. Clin Tech Small Anim Pract 20:240–249Google Scholar
  32. Jenssen H, Hamill P, Hancock RE (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511Google Scholar
  33. Juvvadi PR, Kuroki Y, Arioka M, Nakajima H, Kitamoto K (2003) Functional analysis of the calcineurin-encoding gene cnaA from Aspergillus oryzae: evidence for its putative role in stress adaptation. Arch Microbiol 179:416–422Google Scholar
  34. Kaiserer L, Oberparleiter C, Weiler-Görz R, Burgstaller W, Leiter É, Marx F (2003) Characterization of the Penicillium chrysogenum antifungal protein PAF. Arch Microbiol 180:204–210Google Scholar
  35. Kato M, Aoyama A, Naruse F, Tateyama Y, Hayashi K, Miyazaki M, Papagiannopoulos P, Davis MA, Hynes MJ, Kobayashi T, Tsukagoshi N (1998) The Aspergillus nidulans CCAAT-binding factor AnCP/AnCF is a heteromeric protein analogous to the HAP complex of Saccharomyces cerevisiae. Mol Gen Genet 257:404–411Google Scholar
  36. Kopecka M, Gabriel M (1992) The influence of Congo Red on the cell wall and (1–3)-β-d-glucan microfibril biogenesis in Saccharomyces cerevisiae. Arch Microbiol 158:115–126Google Scholar
  37. Kudla B, Caddick MX, Langdon T, Martinez-Rossi NM, Bennett CF, Sibley S, Davies RW, Arst HN Jr. (1990) The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J 9:1355–1364Google Scholar
  38. Kulmburg P, Mathieu M, Dowzer C, Kelly J, Felenbok B (1993) Specific binding sites in the alcR and alcA promoters of the ethanol regulon for the CREA repressor mediating carbon catabolite repression in Aspergillus nidulans. Mol Microbiol 7:847–857Google Scholar
  39. Lacadena J, Martínez del Pozo A, Gasset M, Patiño B, Campos-Olivas R, Vázquez C, Martínez-Ruiz A, Mancheño JM, Oñaderra M, Gavilanes JG (1995) Characterization of the antifungal protein secreted by the mould Aspergillus giganteus. Arch Biochem Biophys 324:273–281Google Scholar
  40. Lamb TM, Mitchell AP (2003) The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol Cell Biol 23:677–686Google Scholar
  41. Li DW, Yang CS (2004) Fungal contamination as a major contributor to sick building syndrome. Adv Appl Microbiol 55:31–112CrossRefGoogle Scholar
  42. Li S, Du L, Yuen G, Harris SD (2006) Distinct ceramide synthases regulate polarized growth in the filamentous fungus Aspergillus nidulans. Mol Biol Cell 17:1218–1227Google Scholar
  43. Liu RS, Huang H, Yang Q, Liu WY (2002) Purification of α-sarcin and an antifungal protein from mold (Aspergillus giganteus) by chitin affinity chromatography. Protein Expr Purif 25:50–58Google Scholar
  44. Liu H, Kauffman S, Becker JM, Szaniszlo PJ (2004) Wangiella (Exophiala) dermatitidis WdChs5p, a class V chitin synthase, is essential for sustained cell growth at temperature of infection. Eukaryot Cell 3:40–51Google Scholar
  45. Madrid MP, Di Pietro A, Roncero MI (2003) Class V chitin synthase determines pathogenesis in the vascular wilt fungus Fusarium oxysporum and mediates resistance to plant defence compounds. Mol Microbiol 47:257–266Google Scholar
  46. Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, Estruch F (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15:2227–2235Google Scholar
  47. Martínez-Ruiz A, Martínez del Pozo A, Lacadena J, Mancheño JM, Oñaderra M, Gavilanes JG (1997) Characterization of a natural larger form of the antifungal protein (AFP) from Aspergillus giganteus. Biochim Biophys Acta 1340:81–87Google Scholar
  48. Martínez Del Pozo A, Lacadena V, Mancheño JM, Olmo N, Oñaderra M, Gavilanes JG (2002) The antifungal protein AFP of Aspergillus giganteus is an oligonucleotide/oligosaccharide binding (OB) fold-containing protein that produces condensation of DNA. J Biol Chem 277:46179–46183Google Scholar
  49. Marx F (2004) Small, basic antifungal proteins secreted from filamentous ascomycetes: a comparative study regarding expression, structure, function and potential application. Appl Microbiol Biotechnol 65:133–142Google Scholar
  50. Marx F, Haas H, Reindl M, Stoffler G, Lottspeich F, Redl B (1995) Cloning, structural organization and regulation of expression of the Penicillium chrysogenum paf gene encoding an abundantly secreted protein with antifungal activity. Gene 167:167–171Google Scholar
  51. Marx F, Salvenmoser W, Kaiserer L, Graessle S, Weiler-Görz R, Zadra I, Oberparleiter C (2005) Proper folding of the antifungal protein PAF is required for optimal activity. Res Microbiol 156:35–46Google Scholar
  52. Marx F, Binder U, Leiter É, Pócsi I (2007) The Penicillium chrysogenum antifungal protein PAF, a promising tool for the development of new antifungal therapies and fungal cell biology studies. Cell Mol Life Sci, doi:10.1007/s00018-007-7364-8
  53. Masia Canuto M, Gutierrez Rodero F (2002) Antifungal drug resistance to azoles and polyenes. Lancet Infect Dis 2:550–563Google Scholar
  54. Mellado E, Aufauvre-Brown A, Gow NA, Holden DW (1996) The Aspergillus fumigatus chsC and chsG genes encode class III chitin synthases with different functions. Mol Microbiol 20:667–679Google Scholar
  55. Mellado E, Dubreucq G, Mol P, Sarfati J, Paris S, Diaquin M, Holden DW, Rodríiguez-Tudela JL, Latge JP (2003) Cell wall biogenesis in a double chitin synthase mutant (chsG–/chsE–) of Aspergillus fumigatus. Fungal Genet Biol 38:98–109Google Scholar
  56. Mellado E, Alcázar-Fuoli L, Garcia-Effron G, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodríguez-Tudela JL (2006) New resistance mechanisms to azole drugs in Aspergillus fumigatus and emergence of antifungal drugs-resistant A. fumigatus atypical strains. Med Mycol 44(Suppl):367–371Google Scholar
  57. Meyer V, Stahl U (2002) New insights in the regulation of the afp gene encoding the antifungal protein of Aspergillus giganteus. Curr Genet 42:36–42Google Scholar
  58. Meyer V, Stahl U (2003) The influence of co-cultivation on expression of the antifungal protein in Aspergillus giganteus. J Basic Microbiol 43:68–74Google Scholar
  59. Meyer V, Wedde M, Stahl U (2002) Transcriptional regulation of the antifungal protein in Aspergillus giganteus. Mol Genet Genomics 266:747–757Google Scholar
  60. Meyer V, Spielvogel A, Funk L, Tilburn J, Arst HN Jr., Stahl U (2005) Alkaline pH-induced up-regulation of the afp gene encoding the antifungal protein (AFP) of Aspergillus giganteus is not mediated by the transcription factor PacC: possible involvement of calcineurin. Mol Genet Genomics 274:295–306Google Scholar
  61. Moreno AB, Peñas G, Rufat M, Bravo JM, Estopa M, Messeguer J, San Segundo B (2005) Pathogen-induced production of the antifungal AFP protein from Aspergillus giganteus confers resistance to the blast fungus Magnaporthe grisea in transgenic rice. Mol Plant Microbe Interact 18:960–972Google Scholar
  62. Moreno AB, Martínez Del Pozo A, San Segundo B (2006) Biotechnologically relevant enzymes and proteins. Antifungal mechanism of the Aspergillus giganteus AFP against the rice blast fungus Magnaporthe grisea. Appl Microbiol Biotechnol 72:883–895Google Scholar
  63. Mouyna I, Henry C, Doering TL, Latge JP (2004) Gene silencing with RNA interference in the human pathogenic fungus Aspergillus fumigatus. FEMS Microbiol Lett 237:317–324Google Scholar
  64. Muller C, Hjort CM, Hansen K, Nielsen J (2002) Altering the expression of two chitin synthase genes differentially affects the growth and morphology of Aspergillus oryzae. Microbiology 148:4025–4033Google Scholar
  65. Murzin AG (1993) OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. EMBO J 12:861–867Google Scholar
  66. Nakaya K, Omata K, Okahashi I, Nakamura Y, Kolekenbrock H, Ulbrich N (1990) Amino acid sequence and disulfide bridges of an antifungal protein isolated from Aspergillus giganteus. Eur J Biochem 193:31–38Google Scholar
  67. Oberparleiter C, Kaiserer L, Haas H, Ladurner P, Andratsch M, Marx F (2003) Active internalization of the Penicillium chrysogenum antifungal protein PAF in sensitive Aspergilli. Antimicrob Agents Chemother 47:3598–3601Google Scholar
  68. Odenbach D, Breth B, Thines E, Weber RW, Anke H, Foster AJ (2007) The transcription factor Con7p is a central regulator of infection-related morphogenesis in the rice blast fungus Magnaporthe grisea. Mol Microbiol 64:293–307Google Scholar
  69. Ohara T, Tsuge T (2004) FoSTUA, encoding a basic helix–loop–helix protein, differentially regulates development of three kinds of asexual spores, macroconidia, microconidia, and chlamydospores, in the fungal plant pathogen Fusarium oxysporum. Eukaryot Cell 3:1412–1422Google Scholar
  70. Oldach KH, Becker D, Lörz H (2001) Heterologous expression of genes mediating enhanced fungal resistance in transgenic wheat. Mol Plant Microbe Interact 14:832–838Google Scholar
  71. Oshima Y (1997) The phosphatase system in Saccharomyces cerevisiae. Genes Genet Syst 72:323–334Google Scholar
  72. Park C, Bennion B, Francois IE, Ferket KK, Cammue BP, Thevissen K, Levery SB (2005) Neutral glycolipids of the filamentous fungus Neurospora crassa: altered expression in plant defensin-resistant mutants. J Lipid Res 46:759–768Google Scholar
  73. Rasmussen C, Garen C, Brining S, Kincaid RL, Means RL, Means AR (1994) The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans. EMBO J 13:3917–3924Google Scholar
  74. Riquelme M, Bartnicki-García S, González-Prieto JM, Sánchez-León E, Verdin-Ramos JA, Beltrán-Aguilar A, Freitag M (2007) Spitzenkörper localization and intracellular traffic of GFP-labeled CHS-3 and CHS-6 chitin synthases in living hyphae of Neurospora crassa. Eukaryot Cell 6:1853–1864Google Scholar
  75. Roncero C (2002) The genetic complexity of chitin synthesis in fungi. Curr Genet 41:367–378Google Scholar
  76. Roncero C, Valdivieso MH, Ribas JC, Duran A (1988) Effect of calcofluor white on chitin synthases from Saccharomyces cerevisiae. J Bacteriol 170:1945–1949Google Scholar
  77. Ruiz-Herrera J, Martinez-Espinoza AD (1999) Chitin biosynthesis and structural organization in vivo. Exs 87:39–53Google Scholar
  78. Ruiz-Herrera J, Lopez-Romero E, Bartnicki-García S (1977) Properties of chitin synthetase in isolated chitosomes from yeast cells of Mucor rouxii. J Biol Chem 252:3338–3343Google Scholar
  79. Sanz Alonso MA, Jarque Ramos I, Salavert Lleti M, Peman J (2006) Epidemiology of invasive fungal infections due to Aspergillus spp. and Zygomycetes. Clin Microbiol Infect 12(Suppl 7):2–6Google Scholar
  80. Sarfati J, Diaquin M, Debeaupuis JP, Schmidt A, Lecaque D, Beauvais A, Latge JP (2002) A new experimental murine aspergillosis model to identify strains of Aspergillus fumigatus with reduced virulence. Nippon Ishinkin Gakkai Zasshi 43:203–213Google Scholar
  81. Schmidt A (2002) Animal models of aspergillosis—also useful for vaccination strategies? Mycoses 45:38–40Google Scholar
  82. Serrano R, Ruiz A, Bernal D, Chambers JR, Ariño J (2002) The transcriptional response to alkaline pH in Saccharomyces cerevisiae: evidence for calcium-mediated signalling. Mol Microbiol 46:1319–1333Google Scholar
  83. Sietsma JH, Beth Din A, Ziv V, Sjollema KA, Yarden O (1996) The localization of chitin synthase in membranous vesicles (chitosomes) in Neurospora crassa. Microbiology 142(Pt 7):1591–1596Google Scholar
  84. Sorger PK (1990) Yeast heat shock factor contains separable transient and sustained response transcriptional activators. Cell 62:793–805Google Scholar
  85. Steinbach WJ, Cramer RA Jr., Perfect BZ, Asfaw YG, Sauer TC, Najvar LK, Kirkpatrick WR, Patterson TF, Benjamin DK Jr., Heitman J, Perfect JR (2006) Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot Cell 5:1091–1103Google Scholar
  86. Steinbach WJ, Cramer RA Jr., Perfect BZ, Henn C, Nielsen K, Heitman J, Perfect JR (2007a) Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus. Antimicrob Agents Chemother 51:2979–2981Google Scholar
  87. Steinbach WJ, Reedy JL, Cramer RA Jr., Perfect JR, Heitman J (2007b) Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Microbiol 5:418–430Google Scholar
  88. Straus DC, Cooley JD, Wong WC, Jumper CA (2003) Studies on the role of fungi in Sick Building Syndrome. Arch Environ Health 58:475–478Google Scholar
  89. Suárez T, Peñalva MA (1996) Characterization of a Penicillium chrysogenum gene encoding a PacC transcription factor and its binding sites in the divergent pcbAB–pcbC promoter of the penicillin biosynthetic cluster. Mol Microbiol 20:529–540Google Scholar
  90. Szappanos H, Szigeti GP, Pál B, Rusznák Z, Szűcs G, Rajnavölgyi E, Balla J, Balla G, Nagy E, Leiter É, Pócsi I, Marx F, Csernoch L (2005) The Penicillium chrysogenum-derived antifungal peptide shows no toxic effects on mammalian cells in the intended therapeutic concentration. Naunyn Schmiedebergs Arch Pharmacol 371:122–132Google Scholar
  91. Szappanos H, Szigeti GP, Pál B, Rusznák Z, Szűcs G, Rajnavölgyi E, Balla J, Balla G, Nagy E, Leiter É, Pócsi I, Hagen S, Meyer V, Csernoch L (2006) The antifungal protein AFP secreted by Aspergillus giganteus does not cause detrimental effects on certain mammalian cells. Peptides 27:1717–1725Google Scholar
  92. Takeshita N, Ohta A, Horiuchi H (2005) CsmA, a class V chitin synthase with a myosin motor-like domain, is localized through direct interaction with the actin cytoskeleton in Aspergillus nidulans. Mol Biol Cell 16:1961–1970Google Scholar
  93. Talbot NJ (2003) On the trail of a cereal killer: exploring the biology of Magnaporthe grisea. Annu Rev Microbiol 57:177–202Google Scholar
  94. Theis T, Stahl U (2004) Antifungal proteins: targets, mechanisms and prospective applications. Cell Mol Life Sci 61:437–455Google Scholar
  95. Theis T, Wedde M, Meyer V, Stahl U (2003) The antifungal protein from Aspergillus giganteus causes membrane permeabilization. Antimicrob Agents Chemother 47:588–593Google Scholar
  96. Theis T, Marx F, Salvenmoser W, Stahl U, Meyer V (2005) New insights into the target site and mode of action of the antifungal protein of Aspergillus giganteus. Res Microbiol 156:47–56Google Scholar
  97. Thevissen K, Ferket KK, Francois IE, Cammue BP (2003) Interactions of antifungal plant defensins with fungal membrane components. Peptides 24:1705–1712Google Scholar
  98. Tilburn J, Sarkar S, Widdick DA, Espeso EA, Orejas M, Mungroo J, Peñalva MA, Arst HN Jr. (1995) The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J 14:779–790Google Scholar
  99. Vila L, Lacadena V, Fontanet P, Martínez del Pozo A, San Segundo B (2001) A protein from the mold Aspergillus giganteus is a potent inhibitor of fungal plant pathogens. Mol Plant Microbe Interact 14:1327–1331Google Scholar
  100. Viladevall L, Serrano R, Ruiz A, Domenech G, Giraldo J, Barcelo A, Ariño J (2004) Characterization of the calcium-mediated response to alkaline stress in Saccharomyces cerevisiae. J Biol Chem 279:43614–43624Google Scholar
  101. Wagner C, Graninger W, Presterl E, Joukhadar C (2006) The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology 78:161–177Google Scholar
  102. Wang Z, Zheng L, Liu H, Wang Q, Hauser M, Kauffman S, Becker JM, Szaniszlo PJ (2001) WdChs2p, a class I chitin synthase, together with WdChs3p (class III) contributes to virulence in Wangiella (Exophiala) dermatitidis. Infect Immun 69:7517–7526Google Scholar
  103. Weber I, Assmann D, Thines E, Steinberg G (2006) Polar localizing class V myosin chitin synthases are essential during early plant infection in the plant pathogenic fungus Ustilago maydis. Plant Cell 18:225–242Google Scholar
  104. Wiederhold NP, Lewis JS 2nd (2007) The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother 8:1155–1166Google Scholar
  105. Wnendt S, Ulbrich N, Stahl U (1990) Cloning and nucleotide sequence of a cDNA encoding the antifungal-protein of Aspergillus giganteus and preliminary characterization of the native gene. Nucleic Acids Res 18:3987Google Scholar
  106. Wnendt S, Ulbrich N, Stahl U (1994) Molecular cloning, sequence analysis and expression of the gene encoding an antifungal-protein from Aspergillus giganteus. Curr Genet 25:519–523Google Scholar
  107. Wu J, Miller BL (1997) Aspergillus asexual reproduction and sexual reproduction are differentially affected by transcriptional and translational mechanisms regulating stunted gene expression. Mol Cell Biol 17:6191–6201Google Scholar
  108. Wu D, Dou X, Hashmi SB, Osmani SA (2004) The Pho80-like cyclin of Aspergillus nidulans regulates development independently of its role in phosphate acquisition. J Biol Chem 279:37693–37703Google Scholar
  109. Yoshida K, Ogawa N, Oshima Y (1989) Function of the PHO regulatory genes for repressible acid phosphatase synthesis in Saccharomyces cerevisiae. Mol Gen Genet 217:40–46Google Scholar
  110. Yoshimoto H, Saltsman K, Gasch AP, Li HX, Ogawa N, Botstein D, Brown PO, Cyert MS (2002) Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. J Biol Chem 277:31079–31088Google Scholar
  111. Zhang X, Lester RL, Dickson RC (2004) Pil1p and Lsp1p negatively regulate the 3-phosphoinositide-dependent protein kinase-like kinase Pkh1p and downstream signaling pathways Pkc1p and Ypk1p. J Biol Chem 279:22030–22038Google Scholar
  112. Zvyagilskaya R, Parchomenko O, Abramova N, Allard P, Panaretakis T, Pattison-Granberg J, Persson BL (2001) Proton- and sodium-coupled phosphate transport systems and energy status of Yarrowia lipolytica cells grown in acidic and alkaline conditions. J Membr Biol 183:39–50Google Scholar

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© Springer-Verlag 2007

Authors and Affiliations

  1. 1.TU Berlin, Institut für Biotechnologie, Fachgebiet Mikrobiologie und GenetikBerlinGermany

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