SreA-mediated iron regulation in Aspergillus fumigatus

Molecular Microbiology

Volumn 70, Issue 1, 2008, Pages 27-43

  Schrettl, Markus ^a   Kim, H Stanley ^b   Eisendle, Martin ^a   Kragl, Claudia ^a   Nierman, William C ^c,d   Heinekamp, Thorsten ^e   Werner, Ernst R ^a   Jacobsen, Ilse ^e   Illmer, Paul ^f   Yi, Hyojeong ^b   Brakhage, Axel A ^e   Haas, Hubertus ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b Korea University College of Medicine   (South Korea)

^c J CRAIG VENTER INSTITUTE   (United States)

^d GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND HEALTH SCIENCES   (United States)

^e FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^f UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; IRON; MENADIONE; PHLEOMYCIN; PROTEIN SREA; SIDEROPHORE; TRANSCRIPTION FACTOR GATA; UNCLASSIFIED DRUG;

ARTICLE; ASPERGILLUS FUMIGATUS; BACTERIAL INFECTION; BACTERIAL STRAIN; CONTROLLED STUDY; DNA MICROARRAY; GENE EXPRESSION; GENETIC COMPLEMENTATION; IRON DEPLETION; IRON METABOLISM; IRON TRANSPORT; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEFICIENCY; REGULON;

ASPERGILLUS FUMIGATUS; DNA, FUNGAL; FERRIC COMPOUNDS; FERRICHROME; FUNGAL PROTEINS; GATA TRANSCRIPTION FACTORS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, FUNGAL; GENES, FUNGAL; GENETIC COMPLEMENTATION TEST; HYDROXAMIC ACIDS; IRON; MOLECULAR SEQUENCE DATA; MUTATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OXIDATIVE STRESS; PROMOTER REGIONS (GENETICS); REGULON; REPRESSOR PROTEINS; RNA, FUNGAL; SIDEROPHORES; VIRULENCE;

ASPERGILLUS FUMIGATUS;

EID: 51649095152     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/j.1365-2958.2008.06376.x     Document Type: Article

References (80)

1. An, Z., Mei, B., Yuan, W.M. Leong, S.A. (1997) The distal GATA sequences of the sid1 promoter of Ustilago maydis mediate iron repression of siderophore production and interact directly with Urbs1, a GATA family transcription factor. EMBO J 16 : 1742 1750.
2. Andrade, A.C., Van Nistelrooy, J.G., Peery, R.B., Skatrud, P.L. De Waard, M.A. (2000) The role of ABC transporters from Aspergillus nidulans in protection against cytotoxic agents and in antibiotic production. Mol Gen Genet 263 : 966 977.
3. Bhabhra, R., Miley, M.D., Mylonakis, E., Boettner, D., Fortwendel, J., Panepinto, J.C., et al. (2004) Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect Immun 72 : 4731 4740.
4. Blaiseau, P.L., Lesuisse, E. Camadro, J.M. (2001) Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast. J Biol Chem 276 : 34221 34226.
5. Comporti, M. (1989) Three models of free radical-induced cell injury. Chem Biol Interact 72 : 1 56.
6. Eichhorn, H., Lessing, F., Winterberg, B., Schirawski, J., Kamper, J., Muller, P. Kahmann, R. (2006) A ferroxidation/permeation iron uptake system is required for virulence in Ustilago maydis. Plant Cell 18 : 3332 3345.
7. Eisendle, M., Oberegger, H., Zadra, I. Haas, H. (2003) The siderophore system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding 1-ornithine N 5-monooxygenase (sidA) and a non-ribosomal peptide synthetase (sidC). Mol Microbiol 49 : 359 375.
8. Eisendle, M., Schrettl, M., Kragl, C., Muller, D., Illmer, P. Haas, H. (2006) The intracellular siderophore ferricrocin is involved in iron storage, oxidative-stress resistance, germination, and sexual development in Aspergillus nidulans. Eukaryot Cell 5 : 1596 1603.
9. Emery, T. (1976) Fungal ornithine esterases: relationship to iron transport. Biochemistry 15 : 2723 2728.
10. Fluckinger, M., Haas, H., Merschak, P., Glasgow, B.J. Redl, B. (2004) Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob Agents Chemother 48 : 3367 3372.
11. Greenshields, D., Guosheng, L., Feng, J., Selvaraj, G. Wei, Y. (2007) The siderophore biosynthetic gene SID1, but not the ferroxidase gene FET3, is required for full Fusarium graminearum virulence. Mol Plant Path 8 : 411 421.
12. Haas, H. (2003) Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl Microbiol Biotechnol 62 : 316 330.
13. Haas, H., Angermayr, K. Stoffler, G. (1997) Molecular analysis of a Penicillium chrysogenum GATA factor encoding gene (sreP) exhibiting significant homology to the Ustilago maydis urbs1 gene. Gene 184 : 33 37.
14. Haas, H., Zadra, I., Stoffler, G. Angermayr, K. (1999) The Aspergillus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake. J Biol Chem 274 : 4613 4619.
15. Haas, H., Schoeser, M., Lesuisse, E., Ernst, J.F., Parson, W., et al. (2003) Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C. Biochem J 371 : 505 513.
16. Haber, F. Weiss, J. (1934) The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc Series A 147 : 332 333.
17. Hachem, R., Bahna, P., Hanna, H., Stephens, L.C. Raad, I. (2006) EDTA as an adjunct antifungal agent for invasive pulmonary aspergillosis in a rodent model. Antimicrob Agents Chemother 50 : 1823 1827.
18. Halliwell, B. Gutteridge, J.M. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219 : 1 14.
19. Harrison, K.A. Marzluf, G.A. (2002) Characterization of DNA binding and the cysteine rich region of SRE, a GATA factor in Neurospora crassa involved in siderophore synthesis. Biochemistry 41 : 15288 15295.
20. Heymann, P., Gerads, M., Schaller, M., Dromer, F., Winkelmann, G. Ernst, J.F. (2002) The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70 : 5246 5255.
21. Hissen, A.H., Wan, A.N., Warwas, M.L., Pinto, L.J. Moore, M.M. (2005) The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding 1-ornithine N5-oxygenase, is required for virulence. Infect Immun 73 : 5493 5503.
22. Hof, C., Eisfeld, K., Welzel, K., Antelo, L., Foster, A.J. Anke, H. (2007) Ferricrocin synthesis in Magnaporthae grisaea and its role in pathogenicity in rice. Mol Plant Pathol 8 : 163 172.
23. Hortschansky, P., Eisendle, M., Al-Abdallah, Q., Schmidt, A.D., Bergmann, S., Thon, M., et al. (2007) Interaction of HapX with the CCAAT-binding complex - a novel mechanism of gene regulation by iron. EMBO J 26 : 3157 3168.
24. Hu, C.J., Bai, C., Zheng, X.D., Wang, Y.M. Wang, Y. (2002) Characterization and functional analysis of the siderophore-Fe transporter CaArn1p in Candida albicans. J Biol Chem 277 : 30598 30605.
25. Jung, W.H., Sham, A., White, R. Kronstad, J.W. (2006) Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans. PLoS Biol 4 : e410.
26. Kontoyiannis, D.P., Chamilos, G., Lewis, R.E., Giralt, S., Cortes, J., Raad, I.I., et al. (2007) Increased bone marrow iron stores is an independent risk factor for invasive aspergillosis in patients with high-risk hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation. Cancer 110 : 1303 1306.
27. Kosman, D.J. (2003) Molecular mechanisms of iron uptake in fungi. Mol Microbiol 47 : 1185 1197.
28. Kragl, C., Schrettl, M., Abt, B., Sarg, B., Lindner, H.H. Haas, H. (2007) EstB-mediated hydrolysis of the siderophore triacetylfusarinine C optimizes iron uptake of Aspergillus fumigatus. Eukaryot Cell 6 : 1278 1285.
29. Kupfahl, C., Heinekamp, T., Geginat, G., Ruppert, T., Hartl, A., Hof, H. Brakhage, A.A. (2006) Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low-dose mouse infection model. Mol Microbiol 62 : 292 302.
30. Lacadena, J., Alvarez-Garcia, E., Carreras-Sangra, N., Herrero-Galan, E., Alegre-Cebollada, J., Garcia-Ortega, L., et al. (2007) Fungal ribotoxins: molecular dissection of a family of natural killers. FEMS Microbiol Rev 31 : 212 237.
31. Lan, C.Y., Rodarte, G., Murillo, L.A., Jones, T., Davis, R.W., Dungan, J., et al. (2004) Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol 53 : 1451 1469.
32. Latge, J.P. (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12 : 310 350.
33. Leong, S.A. Winkelmann, G. (1998) Molecular biology of iron transport in fungi. Met Ions Biol Syst 35 : 147 186.
34. Lessing, F., Kniemeyer, O., Wozniok, I., Loeffler, J., Kurzai, O., Haertl, A. Brakhage, A.A. (2007) The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot Cell 6 : 2290 2302.
35. Lesuisse, E., Blaiseau, P.L., Dancis, A. Camadro, J.M. (2001) Siderophore uptake and use by the yeast Saccharomyces cerevisiae. Microbiology 147 : 289 298.
36. Li, L., Chen, O.S., McVey Ward, D. Kaplan, J. (2001) CCC1 is a transporter that mediates vacuolar iron storage in yeast. J Biol Chem 276 : 29515 29519.
37. Lian, T., Simmer, M.I., D'Souza, C.A., Steen, B.R., Zuyderduyn, S.D., Jones, S.J., et al. (2005) Iron-regulated transcription and capsule formation in the fungal pathogen Cryptococcus neoformans. Mol Microbiol 55 : 1452 1472.
38. Liebmann, B., Muhleisen, T.W., Muller, M., Hecht, M., Weidner, G., Braun, A., et al. (2004) Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose mouse infection model of invasive aspergillosis. Arch Microbiol 181 : 378 383.
39. Lupas, A., Van Dyke, M. Stock, J. (1991) Predicting coiled coils from protein sequences. Science 252 : 1162 1164.
40. McDonnell, A.V., Jiang, T., Keating, A.E. Berger, B. (2006) Paircoil2: improved prediction of coiled coils from sequence. Bioinformatics 22 : 356 358.
41. Marr, K.A., Patterson, T. Denning, D. (2002) Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Am 16 : 875 894, vi.
42. Martins, L.J., Jensen, L.T., Simon, J.R., Keller, G.L., Winge, D.R. Simons, J.R. (1998) Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae. J Biol Chem 273 : 23716 23721.
43. Mercier, A., Watt, S., Bahler, J. Labbe, S. (2008) Key function for the CCAAT-binding factor Php4 to regulate gene expression in response to iron deficiency in fission yeast. Eukaryot Cell 7 : 493 508.
44. Nierman, W.C., Pain, A., Anderson, M.J., Wortman, J.R., Kim, H.S., Arroyo, J., et al. (2005) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438 : 1151 1156.
45. Oberegger, H., Schoeser, M., Zadra, I., Abt, B. Haas, H. (2001) SREA is involved in regulation of siderophore biosynthesis, utilization and uptake in Aspergillus nidulans. Mol Microbiol 41 : 1077 1089.
46. Oberegger, H., Zadra, I., Schoeser, M., Abt, B., Parson, W. Haas, H. (2002a) Identification of members of the Aspergillus nidulans SREA regulon: genes involved in siderophore biosynthesis and utilization. Biochem Soc Trans 30 : 781 783.
47. Oberegger, H., Schoeser, M., Zadra, I., Schrettl, M., Parson, W. Haas, H. (2002b) Regulation of freA, acoA, lysF, and cycA expression by iron availability in Aspergillus nidulans. Appl Environ Microbiol 68 : 5769 5772.
48. Oide, S., Moeder, W., Haas, H., Krasnoff, S., Gibson, D., Yoshioka, K. Turgeon, B.G. (2006) NPS6, encoding a non-ribosomal peptide synthetase involved in siderophore-mediated iron metabolism, is a conserved virulence determinant of plant pathogenic ascomycetes. Plant Cell 18 : 2836 2853.
49. Paris, S., Wysong, D., Debeaupuis, J.P., Shibuya, K., Philippe, B., Diamond, R.D. Latge, J.P. (2003) Catalases of Aspergillus fumigatus. Infect Immun 71 : 3551 3562.
50. Pelletier, B., Beaudoin, J., Mukai, Y. Labbe, S. (2002) Fep1, an iron sensor regulating iron transporter gene expression in Schizosaccharomyces pombe. J Biol Chem 277 : 22950 22958.
51. Pelletier, B., Beaudoin, J., Philpott, C.C. Labbe, S. (2003) Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system. Nucleic Acids Res 31 : 4332 4344.
52. Pelletier, B., Trott, A., Morano, K.A. Labbe, S. (2005) Functional characterization of the iron-regulatory transcription factor Fep1 from Schizosaccharomyces pombe. J Biol Chem 280 : 25146 25161.
53. Perrin, R.M., Fedorova, N.D., Bok, J.W., Cramer, R.A., Wortman, J.R., Kim, H.S., et al. (2007) Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLoS Pathog 3 : e50.
54. Philpott, C.C. (2006) Iron uptake in fungi: a system for every source. Biochim Biophys Acta 1763 : 636 645.
55. Plattner, H.J. Diekmann, H. (1994) Enzymology of siderophore biosynthesis in fungi. In Metal Ions in Fungi. Winkelmann, G. Winge, D.R. (eds). New York : New York Marcel Decker, pp. 99 117.
56. Pontecorvo, G., Roper, J.A., Hemmons, L.M., MacDonald, K.D. Bufton, A.W.J. (1953) The genetics of Aspergillus nidulans. Adv Genet 5 : 141 238.
57. Punt, P.J., Oliver, R.P., Dingemanse, M.A., Pouwels, P.H. van den Hondel, C.A. (1987) Transformation of Aspergillus based on the hygromycin B resistance marker from Escherichia coli. Gene 56 : 117 124.
58. Reiber, K., Reeves, E.P., Neville, C.M., Winkler, R., Gebhardt, P., Kavanagh, K. Doyle, S. (2005) The expression of selected non-ribosomal peptide synthetases in Aspergillus fumigatus is controlled by the availability of free iron. FEMS Microbiol Lett 248 : 83 91.
59. Reichard, U., Eiffert, H. Ruchel, R. (1994) Purification and characterization of an extracellular aspartic proteinase from Aspergillus fumigatus. J Med Vet Mycol 32 : 427 436.
60. Reichard, U., Monod, M. Ruchel, R. (1995) Molecular cloning and sequencing of the gene encoding an extracellular aspartic proteinase from Aspergillus fumigatus. FEMS Microbiol Lett 130 : 69 74.
61. Sambrook, J., Fritsch, E.F. Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. New York : Cold Spring Harbor Laboratory Press.
62. Sanz, L., Montero, M., Redondo, J., Llobell, A. Monte, E. (2005) Expression of an alpha-1,3-glucanase during mycoparasitic interaction of Trichoderma asperellum. FEBS J 272 : 493 499.
63. Schardl, C.L. (2006) A global view of metabolites. Chem Biol 13 : 5 6.
64. Schrettl, M., Bignell, E., Kragl, C., Joechl, C., Rogers, T., Arst, H.N., Jr, et al. (2004a) Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med 200 : 1213 1219.
65. Schrettl, M., Winkelmann, G. Haas, H. (2004b) Ferrichrome in Schizosaccharomyces pombe- an iron transport and iron storage compound. Biometals 17 : 647 654.
66. Schrettl, M., Bignell, E., Kragl, C., Sabiha, Y., Loss, O., Eisendle, M., et al. (2007) Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog 3 : 1195 1207.
67. Tilburn, J., Sarkar, S., Widdick, D.A., Espeso, E.A., Orejas, M., Mungroo, J., et al. (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.
68. Tobin, M.B., Peery, R.B. Skatrud, P.L. (1997) Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene 200 : 11 23.
69. Trainor, C.D., Omichinski, J.G., Vandergon, T.L., Gronenborn, A.M., Clore, G.M. Felsenfeld, G. (1996) A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction. Mol Cell Biol 16 : 2238 2247.
70. Voisard, C., Wang, J., McEvoy, J.L., Xu, P. Leong, S.A. (1993) urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Biol 13 : 7091 7100.
71. Weinberg, E.D. (1993) The development of awareness of iron-withholding defense. Perspect Biol Med 36 : 215 221.
72. Weinberg, E.D. (1999) The role of iron in protozoan and fungal infectious diseases. J Eukaryot Microbiol 46 : 231 238.
73. Weiss, G. (2002) Iron and immunity: a double-edged sword. Eur J Clin Invest 32 (Suppl. 1 70 78.
74. Winkelmann, G. (1993) Kinetics, energetics, and mechanisms of siderophore iron transport in fungi. In Iron Chelation in Plants and Soil Microorganisms. Barton, L.L. Hemming, B.C. (ed.). New York : New York Academic Press, pp. 219 239.
75. Winkelmann, G. (2001) Siderophore transport in fungi. In Microbial Trasnport Systems. Winkelmann, G. (ed.). Weinheim : Wiley-VCH, pp. 463 480.
76. Winkelmann, G. (2007) Ecology of siderophores with special reference to the fungi. Biometals 20 : 379 392.
77. Yamaguchi-Iwai, Y., Dancis, A. Klausner, R.D. (1995) AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. EMBO J 14 : 1231 1239.
78. Yuan, W.M., Gentil, G.D., Budde, A.D. Leong, S.A. (2001) Characterization of the Ustilago maydis sid2 gene, encoding a multidomain peptide synthetase in the ferrichrome biosynthetic gene cluster. J Bacteriol 183 : 4040 4051.
79. Zarember, K.A., Sugui, J.A., Chang, Y.C., Kwon-Chung, K.J. Gallin, J.I. (2007) Human polymorphonuclear leukocytes inhibit Aspergillus fumigatus conidial growth by lactoferrin-mediated iron depletion. J Immunol 178 : 6367 6373.
80. Zhou, L.W., Haas, H. Marzluf, G.A. (1998) Isolation and characterization of a new gene, sre, which encodes a GATA-type regulatory protein that controls iron transport in Neurospora crassa. Mol Gen Genet 259 : 532 540.