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

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Abstract

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.

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References

  • Arcus V (2002) OB-fold domains: a snapshot of the evolution of sequence, structure and function. Curr Opin Struct Biol 12:794–801

    Article  CAS  PubMed  Google Scholar 

  • Bartnicki-García S (2006) Chitosomes: past, present and future. FEMS Yeast Res 6:957–965

    Article  PubMed  CAS  Google Scholar 

  • Benitez T, Rincon AM, Limon MC, Codon AC (2004) Biocontrol mechanisms of Trichoderma strains. Int Microbiol 7:249–260

    CAS  PubMed  Google Scholar 

  • 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 44:621–631

    Article  CAS  PubMed  Google Scholar 

  • 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 73:4570–4574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 17:3990–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 34:3009–3021

    Article  CAS  PubMed  Google Scholar 

  • Cappelletty D, Eiselstein-McKitrick K (2007) The echinocandins. Pharmacotherapy 27:369–388

    Article  CAS  PubMed  Google Scholar 

  • 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 54:245–259

    Article  CAS  PubMed  Google Scholar 

  • Cohen E (2001) Chitin synthesis and inhibition: a revisit. Pest Manag Sci 57:946–950

    Article  CAS  PubMed  Google Scholar 

  • Cyert MS (2003) Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem Biophys Res Commun 311:1143–1150

    Article  CAS  PubMed  Google Scholar 

  • 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 58:305–319

    Article  CAS  PubMed  Google Scholar 

  • De Lucca AJ, Walsh TJ (1999) Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob Agents Chemother 43:1–11

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 6:3029–3039

    Article  CAS  PubMed  Google Scholar 

  • 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 165:1105–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutton JR, Johns S, Miller BL (1997) StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans. EMBO J 16:5710–5721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 48:4491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edwards SG (2004) Influence of agricultural practices on Fusarium infection of cereals and subsequent contamination of grain by trichothecene mycotoxins. Toxicol Lett 153:29–35

    Article  CAS  PubMed  Google Scholar 

  • 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 271:28825–28830

    Article  CAS  PubMed  Google Scholar 

  • 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 12:3947–3956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 40:176–185

    Article  CAS  PubMed  Google Scholar 

  • 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 4:1982–1989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Futerman AH, Hannun YA (2004) The complex life of simple sphingolipids. EMBO Rep 5:777–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 45:136–141

    Article  PubMed  CAS  Google Scholar 

  • 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 62:95–101

    Article  CAS  PubMed  Google Scholar 

  • 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 15:313–324

    Article  CAS  PubMed  Google Scholar 

  • 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 263:646–651

    Article  CAS  PubMed  Google Scholar 

  • Gupte M, Kulkarni P, Ganguli BN (2002) Antifungal antibiotics. Appl Microbiol Biotechnol 58:46–57

    Article  CAS  PubMed  Google Scholar 

  • 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 73:2128–2134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 4:225–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 20:240–249

    Article  PubMed  Google Scholar 

  • Jenssen H, Hamill P, Hancock RE (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 179:416–422

    Article  CAS  PubMed  Google Scholar 

  • Kaiserer L, Oberparleiter C, Weiler-Görz R, Burgstaller W, Leiter É, Marx F (2003) Characterization of the Penicillium chrysogenum antifungal protein PAF. Arch Microbiol 180:204–210

    Article  CAS  PubMed  Google Scholar 

  • 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 257:404–411

    Article  CAS  PubMed  Google Scholar 

  • 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 158:115–126

    Article  CAS  PubMed  Google Scholar 

  • 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 9:1355–1364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 7:847–857

    Article  CAS  PubMed  Google Scholar 

  • 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 324:273–281

    Article  CAS  PubMed  Google Scholar 

  • 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 23:677–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li DW, Yang CS (2004) Fungal contamination as a major contributor to sick building syndrome. Adv Appl Microbiol 55:31–112

    Article  CAS  PubMed  Google Scholar 

  • Li S, Du L, Yuen G, Harris SD (2006) Distinct ceramide synthases regulate polarized growth in the filamentous fungus Aspergillus nidulans. Mol Biol Cell 17:1218–1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 25:50–58

    Article  CAS  PubMed  Google Scholar 

  • 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 3:40–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 47:257–266

    Article  CAS  PubMed  Google Scholar 

  • 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 15:2227–2235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 1340:81–87

    Article  PubMed  Google Scholar 

  • 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 277:46179–46183

    Article  PubMed  CAS  Google Scholar 

  • Marx F (2004) Small, basic antifungal proteins secreted from filamentous ascomycetes: a comparative study regarding expression, structure, function and potential application. Appl Microbiol Biotechnol 65:133–142

    Article  CAS  PubMed  Google Scholar 

  • 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 167:167–171

    Article  CAS  PubMed  Google Scholar 

  • 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 156:35–46

    Article  CAS  PubMed  Google Scholar 

  • 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:https://doi.org/10.1007/s00018-007-7364-8

    Article  CAS  Google Scholar 

  • Masia Canuto M, Gutierrez Rodero F (2002) Antifungal drug resistance to azoles and polyenes. Lancet Infect Dis 2:550–563

    Article  PubMed  Google Scholar 

  • 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 20:667–679

    Article  CAS  PubMed  Google Scholar 

  • 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 38:98–109

    Article  CAS  PubMed  Google Scholar 

  • 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):367–371

    Article  CAS  Google Scholar 

  • Meyer V, Stahl U (2002) New insights in the regulation of the afp gene encoding the antifungal protein of Aspergillus giganteus. Curr Genet 42:36–42

    Article  CAS  PubMed  Google Scholar 

  • Meyer V, Stahl U (2003) The influence of co-cultivation on expression of the antifungal protein in Aspergillus giganteus. J Basic Microbiol 43:68–74

    Article  CAS  PubMed  Google Scholar 

  • Meyer V, Wedde M, Stahl U (2002) Transcriptional regulation of the antifungal protein in Aspergillus giganteus. Mol Genet Genomics 266:747–757

    Article  CAS  PubMed  Google Scholar 

  • 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 274:295–306

    Article  CAS  PubMed  Google Scholar 

  • 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 18:960–972

    Article  CAS  PubMed  Google Scholar 

  • 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 72:883–895

    Article  CAS  PubMed  Google Scholar 

  • Mouyna I, Henry C, Doering TL, Latge JP (2004) Gene silencing with RNA interference in the human pathogenic fungus Aspergillus fumigatus. FEMS Microbiol Lett 237:317–324

    CAS  PubMed  Google Scholar 

  • 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 148:4025–4033

    Article  CAS  PubMed  Google Scholar 

  • Murzin AG (1993) OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. EMBO J 12:861–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 193:31–38

    Article  CAS  PubMed  Google Scholar 

  • 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 47:3598–3601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 64:293–307

    Article  CAS  PubMed  Google Scholar 

  • 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 3:1412–1422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldach KH, Becker D, Lörz H (2001) Heterologous expression of genes mediating enhanced fungal resistance in transgenic wheat. Mol Plant Microbe Interact 14:832–838

    Article  CAS  PubMed  Google Scholar 

  • Oshima Y (1997) The phosphatase system in Saccharomyces cerevisiae. Genes Genet Syst 72:323–334

    Article  CAS  PubMed  Google Scholar 

  • 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 46:759–768

    Article  CAS  PubMed  Google Scholar 

  • 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 13:3917–3924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 6:1853–1864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roncero C (2002) The genetic complexity of chitin synthesis in fungi. Curr Genet 41:367–378

    Article  CAS  PubMed  Google Scholar 

  • Roncero C, Valdivieso MH, Ribas JC, Duran A (1988) Effect of calcofluor white on chitin synthases from Saccharomyces cerevisiae. J Bacteriol 170:1945–1949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruiz-Herrera J, Martinez-Espinoza AD (1999) Chitin biosynthesis and structural organization in vivo. Exs 87:39–53

    CAS  PubMed  Google Scholar 

  • 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 252:3338–3343

    Article  CAS  PubMed  Google Scholar 

  • 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):2–6

    Article  Google Scholar 

  • 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 43:203–213

    Article  CAS  Google Scholar 

  • Schmidt A (2002) Animal models of aspergillosis—also useful for vaccination strategies? Mycoses 45:38–40

    Article  CAS  PubMed  Google Scholar 

  • 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 46:1319–1333

    Article  CAS  PubMed  Google Scholar 

  • 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):1591–1596

    Article  CAS  PubMed  Google Scholar 

  • Sorger PK (1990) Yeast heat shock factor contains separable transient and sustained response transcriptional activators. Cell 62:793–805

    Article  CAS  PubMed  Google Scholar 

  • 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 5:1091–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 51:2979–2981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 5:418–430

    Article  CAS  PubMed  Google Scholar 

  • Straus DC, Cooley JD, Wong WC, Jumper CA (2003) Studies on the role of fungi in Sick Building Syndrome. Arch Environ Health 58:475–478

    Article  PubMed  Google Scholar 

  • 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 20:529–540

    Article  PubMed  Google Scholar 

  • 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 371:122–132

    Article  CAS  PubMed  Google Scholar 

  • 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 27:1717–1725

    Article  CAS  PubMed  Google Scholar 

  • 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 16:1961–1970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talbot NJ (2003) On the trail of a cereal killer: exploring the biology of Magnaporthe grisea. Annu Rev Microbiol 57:177–202

    Article  CAS  PubMed  Google Scholar 

  • Theis T, Stahl U (2004) Antifungal proteins: targets, mechanisms and prospective applications. Cell Mol Life Sci 61:437–455

    Article  CAS  PubMed  Google Scholar 

  • Theis T, Wedde M, Meyer V, Stahl U (2003) The antifungal protein from Aspergillus giganteus causes membrane permeabilization. Antimicrob Agents Chemother 47:588–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 156:47–56

    Article  CAS  PubMed  Google Scholar 

  • Thevissen K, Ferket KK, Francois IE, Cammue BP (2003) Interactions of antifungal plant defensins with fungal membrane components. Peptides 24:1705–1712

    Article  CAS  PubMed  Google Scholar 

  • 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 14:779–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 14:1327–1331

    Article  CAS  PubMed  Google Scholar 

  • 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 279:43614–43624

    Article  CAS  PubMed  Google Scholar 

  • Wagner C, Graninger W, Presterl E, Joukhadar C (2006) The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology 78:161–177

    Article  CAS  PubMed  Google Scholar 

  • 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 69:7517–7526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 18:225–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiederhold NP, Lewis JS 2nd (2007) The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother 8:1155–1166

    Article  CAS  PubMed  Google Scholar 

  • 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 18:3987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 25:519–523

    Article  CAS  PubMed  Google Scholar 

  • 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 17:6191–6201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 279:37693–37703

    Article  CAS  PubMed  Google Scholar 

  • Yoshida K, Ogawa N, Oshima Y (1989) Function of the PHO regulatory genes for repressible acid phosphatase synthesis in Saccharomyces cerevisiae. Mol Gen Genet 217:40–46

    Article  CAS  PubMed  Google Scholar 

  • 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 277:31079–31088

    Article  CAS  PubMed  Google Scholar 

  • 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 279:22030–22038

    Article  CAS  PubMed  Google Scholar 

  • 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 183:39–50

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

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.

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Correspondence to Vera Meyer.

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Meyer, V. A small protein that fights fungi: AFP as a new promising antifungal agent of biotechnological value. Appl Microbiol Biotechnol 78, 17–28 (2008). https://doi.org/10.1007/s00253-007-1291-3

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  • DOI: https://doi.org/10.1007/s00253-007-1291-3

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