The Aspergillus fumigatus transcriptional activator CpcA contributes significantly to the virulence of this fungal pathogen

Molecular Microbiology

Volumn 52, Issue 3, 2004, Pages 785-799

  Krappmann, Sven ^a   Bignell, Elaine M ^b   Reichard, Utz ^a   Rogers, Tom ^b   Haynes, Ken ^b   Braus, Gerhard H ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; FUNGAL PROTEIN; PROTEIN CPCA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPERGILLUS FUMIGATUS; CONTROLLED STUDY; ENZYME ACTIVITY; FUNGAL GENE; FUNGAL STRAIN; FUNGAL VIRULENCE; GENE DELETION; GENE LOCUS; GENE SEQUENCE; GENETIC CODE; GENETIC CONSERVATION; IN VIVO STUDY; LUNG ASPERGILLOSIS; MALE; MOLECULAR CLONING; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REPORTER GENE; SACCHAROMYCES CEREVISIAE; STATISTICAL SIGNIFICANCE; SURVIVAL; TRANSCRIPTION INITIATION; UPREGULATION; WILD TYPE;

AMINO ACID SEQUENCE; ANIMALS; ASPERGILLUS FUMIGATUS; BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; HUMANS; MALE; MICE; MOLECULAR SEQUENCE DATA; OPEN READING FRAMES; SEQUENCE ALIGNMENT; SURVIVAL RATE; TRANSCRIPTION FACTORS;

ANIMALIA; ASPERGILLUS; ASPERGILLUS FUMIGATUS; MAMMALIA; MURINAE; SACCHAROMYCES; SACCHAROMYCES CEREVISIAE;

EID: 2442506787     PISSN: 0950382X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1365-2958.2004.04015.x     Document Type: Article

References (74)

1. Albrecht, G., Mösch, H.U., Hoffmann, B., Reusser, U., and Braus, G.H. (1998) Monitoring the Gcn4 protein-mediated response in the yeast Saccharomyces cerevisiae. J Biol Chem 273: 12696-12702.
2. Aufauvre-Brown, A., Brown, J.S., and Holden, D.W. (1998) Comparison of virulence between clinical and environmental isolates of Aspergillus fumigatus. Eur J Clin Microbiol Infect Dis 17: 778-780.
3. Bernard, M., and Latge, J.P. (2001) Aspergillus fumigatus cell wall: composition and biosynthesis. Med Mycol 39 (Suppl. 1): 9-17.
4. Bode, R., Schussler, K., Schmidt, H., Hammer, T., and Birnbaum, D. (1990) Occurrence of the general control of amino acid biosynthesis in yeasts. J Basic Microbiol 30: 31-35.
5. Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.
6. Brakhage, A.A., Langfelder, K., Wanner, G., Schmidt, A., and Jahn, B. (1999) Pigment biosynthesis and virulence. Contrib Microbiol 2: 205-215.
7. Brown, T., and Mackey, K. (1997) Analysis of RNA by Northern and slot blot hybridization. In Current Protocols in Molecular Biology. Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., et al. (eds). New York, NY: John Wiley & Sons, pp. 4.9.1-4.9.16.
8. Brown, J.S., Aufauvre-Brown, A., and Holden, D.W. (1998) Insertional mutagenesis of Aspergillus fumigatus. Mol Gen Genet 259: 327-335.
9. Brown, J.S., Aufauvre-Brown, A., Brown, J., Jennings, J.M., Arst, H., Jr, and Holden, D.W. (2000) Signature-tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity. Mol Microbiol 36: 1371-1380.
10. Carsiotis, M., and Jones, R.F. (1974) Cross-pathway regulation: tryptophan-mediated control of histidine and arginine biosynthetic enzymes in Neurospora crassa. J Bacteriol 119: 889-892.
11. Carsiotis, M., Jones, R.F., and Wesseling, A.C. (1974) Cross-pathway regulation: histidine-mediated control of histidine, tryptophan, and arginine biosynthetic enzymes in Neurospora crassa. J Bacteriol 119: 893-898.
12. Chaveroche, M.K., Ghigo, J.M., and d'Enfert, C. (2000) A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. Nucleic Acids Res 28: E97.
13. Chiang, S.L., and Mekalanos, J.J. (1998) Use of signature-tagged transposon mutagenesis to identify Vibrio cholerae genes critical for colonization. Mol Microbiol 27: 797-805.
14. Dasbach, E.J., Davies, G.M., and Teutsch, S.M. (2000) Burden of aspergillosis-related hospitalizations in the United States. Clin Infect Dis 31: 1524-1528.
15. Denning, D.W., Anderson, M.J., Turner, G., Latge, J.P., and Bennett, J.W. (2002) Sequencing the Aspergillus fumigatus genome. Lancet Infect Dis 2: 251-253.
16. Dower, W.J., Miller, J.F., and Ragsdale, C.W. (1988) High efficiency transformation of E. coli by high voltage electroporation. Nucleic Acids Res 16: 6127-6145.
17. Elble, R. (1992) A simple and efficient procedure for transformation of yeasts. Biotechniques 13: 18-20.
18. d'Enfert, C., Diaquin, M., Delit, A., Wuscher, N., Debeaupuis, J.P., Huerre, M., and Latge, J.P. (1996) Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus. Infect Immun 64: 4401-4405.
19. Feinberg, A.P., and Vogelstein, B. (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132: 6-13.
20. Gaba, A., Wang, Z., Krishnamoorthy, T., Hinnebusch, A.G., and Sachs, M.S. (2001) Physical evidence for distinct mechanisms of translational control by upstream open reading frames. EMBO J 20: 6453-6463.
21. Hanahan, D., Jessee, J., and Bloom, F.R. (1991) Plasmid transformation of Escherichia coli and other bacteria. Methods Enzymol 204: 63-113.
22. Hensel, M., Arst, H.N., Jr, Aufauvre-Brown, A., and Holden, D.W. (1998) The role of the Aspergillus fumigatus areA gene in invasive pulmonary aspergillosis. Mol Gen Genet 258: 553-557.
23. Hinnebusch, A.G. (1985) A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol 5: 2349-2360.
24. Hinnebusch, A.G. (1986) The general control of amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. CRC Crit Rev Biochem 21: 277-317.
25. Hinnebusch, A.G., and Natarajan, K. (2002) Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress. Eukaryot Cell 1: 22-32.
26. Hoffmann, B., Wanke, C., Lapaglia, S.K., and Braus, G.H. (2000) c-Jun and RACK1 homologues regulate a control point for sexual development in Aspergillus nidulans. Mol Microbiol 37: 28-41.
27. Hoffmann, B., Valerius, O., Andermann, M., and Braus, G.H. (2001) Transcriptional autoregulation and inhibition of mRNA translation of amino acid regulator gene cpcA of filamentous fungus Aspergillus nidulans. Mol Biol Cell 12: 2846-2857.
28. Jahn, B., Koch, A., Schmidt, A., Wanner, G., Gehringer, H., Bhakdi, S., and Brakhage, A.A. (1997) Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect Immun 65: 5110-5117.
29. Jahn, B., Boukhallouk, F., Lotz, J., Langfelder, K., Wanner, G., and Brakhage, A.A. (2000) Interaction of human phagocytes with pigmentless Aspergillus conidia. Infect Immun 68: 3736-3739.
30. Käfer, E. (1977) Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations. Adv Genet 19: 33-131.
31. Kolar, M., Punt, P.J., van den Hondel, C.A., and Schwab, H. (1988) Transformation of Penicillium chrysogenum using dominant selection markers and expression of an Escherichia coli lacZ fusion gene. Gene 62: 127-134.
32. Kontoyiannis, D.P., and Bodey, G.P. (2002) Invasive aspergillosis in 2002: an update. Eur J Clin Microbiol Infect Dis 21: 161-172.
33. Krappmann, S., Helmstaedt, K., Gerstberger, T., Eckert, S., Hoffmann, B., Hoppert, M., et al. (1999) The aroC gene of Aspergillus nidulans codes for a monofunctional, allosterically regulated chorlsmate mutase. J Biol Chem 274: 22275-22282.
34. Krappmann, S., Lipscomb, W.N., and Braus, G.H. (2000) Coevolution of transcriptional and allosteric regulation at the chorismate metabolic branch point of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 97: 13585-13590.
35. Langfelder, K., Jahn, B., Gehringer, H., Schmidt, A., Wanner, G., and Brakhage, A.A. (1998) Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence. Med Microbiol Immunol (Berlin) 187: 79-89.
36. Latge, J.P. (2001) The pathobiology of Aspergillus fumigatus. Trends Microbiol 9: 382-389.
37. Latge, J.P., and Calderone, R. (2002) Host-microbe interactions: fungi. Invasive human fungal opportunistic infections. Curr Opin Microbiol 5: 355-358.
38. Lin, S.J., Schranz, J., and Teutsch, S.M. (2001) Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 32: 358-366.
39. Liu, H., Krizek, J., and Bretscher, A. (1992) Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics 132: 665-673.
40. Monod, M., Paris, S., Sarfati, J., Jaton-Ogay, K., Ave, P., and Latge, J.P. (1993) Virulence of alkaline protease-deficient mutants of Aspergillus fumigatus. FEMS Microbiol Lett 106: 39-46.
41. Monod, M., Jaton-Ogay, K., and Reichard, U. (1999) Aspergillus fumigatus-secreted proteases as antigenic molecules and virulence factors. Contrib Microbiol 2: 182-192.
42. Mueller, P.P., and Hinnebusch, A.G. (1986) Multiple upstream AUG codons mediate translational control of GCN4. Cell 45: 201-207.
43. Muyrers, J.P., Zhang, Y., and Stewart, A.F. (2001) Techniques: recombinogenic engineering - new options for cloning and manipulating DNA. Trends Biochem Sci 26: 325-331.
44. Natarajan, K., Meyer, M.R., Jackson, B.M., Slade, D., Roberts, C., Hinnebusch, A.G., and Marton, M.J. (2001) Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. Mol Cell Biol 21: 4347-4368.
45. Oliphant, A.R., Brandl, C.J., and Struhl, K. (1989) Defining the sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: analysis of yeast GCN4 protein. Mol Cell Biol 9: 2944-2949.
46. Oren, I., and Goldstein, N. (2002) Invasive pulmonary aspergillosis. Curr Opin Pulmon Med 8: 195-200.
47. Paluh, J.L., Orbach, M.J., Legerton, T.L., and Yanofsky, C. (1988) The cross-pathway control gene of Neurospora crassa, cpc-1, encodes a protein similar to GCN4 of yeast and the DNA-binding domain of the oncogene v-jun-encoded protein. Proc Natl Acad Sci USA 85: 3728-3732.
48. Panepinto, J.C., Oliver, B.G., Fortwendel, J.R., Smith, D.L., Askew, D.S., and Rhodes, J.C. (2003) Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein RhbA reduces virulence in a model of Invasive pulmonary aspergillosis. Infect Immun 71: 2819-2826.
49. Punt, P.J., and van den Hondel, C.A. (1992) Transformation of filamentous fungi based on hygromycin B and phleomycin resistance markers. Methods Enzymol 216: 447-457.
50. Purnell, D.M. (1973) The effects of specific auxotrophic mutations on the virulence of Aspergillus nidulans for mice. Mycopathol Mycol Appl 50: 195-203.
51. Rees, J.R., Pinner, R.W., Hajjeh, R.A., Brandt, M.E., and Reingold, A.L. (1998) The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-93: results of population-based laboratory active surveillance. Clin Infect Dis 27: 1138-1147.
52. Reichard, U., Buttner, S., Eiffert, H., Staib, F., and Rüchel, R. (1990) Purification and characterisation of an extracellular serine proteinase from Aspergillus fumigatus and its detection in tissue. J Med Microbiol 33: 243-251.
53. Reichard, U., Monod, M., Odds, P., and Rüchel, R. (1997) Virulence of an aspergillopepsin-deficient mutant of Aspergillus fumigatus and evidence for another aspartic proteinase linked to the fungal cell wall. J Med Vet Mycol 35: 189-196.
54. Reichard, U., Cole, G.T., Rüchel, R., and Monod, M. (2000) Molecular cloning and targeted deletion of PEP2 which encodes a novel aspartic proteinase from Aspergillus fumigatus. Int J Med Microbiol 290: 85-96.
55. Saiki, R.K., Bugawan, T.L., Horn, G.T., Mullis, K.B., and Erlich, H.A. (1986) Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature 324: 163-166.
56. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
57. Samson, R.A. (1999) The genus Aspergillus with special regard to the Aspergillus fumigatus group. Contrib Microbiol 2: 5-20.
58. Sandhu, D.K., Sandhu, R.S., Khan, Z.U., and Damodaran, V.N. (1976) Conditional virulence of a p-aminobenzoic acid-requiring mutant of Aspergillus fumigatus. Infect Immun 13: 527-532.
59. Schmidheini, T., Sperisen, P., Paravicini, G., Hutter, R., and Braus, G. (1989) A single point mutation results in a constitutively activated and feedback-resistant chorismate mutase of Saccharomyces cerevisiae. J Bacteriol 171: 1245-1253.
60. Schmidheini, T., Mosch, H.U., Graf, R., and Braus, G.H. (1990) A GCN4 protein recognition element is not sufficient for GCN4-dependent regulation of transcription in the ARO7 promoter of Saccharomyces cerevisiae. Mol Gen Genet 224: 57-64.
61. Sikorski, R.S., and Hieter, P. (1989) A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122: 19-27.
62. Smith, J.M., Tang, C.M., Van Noorden, S., and Holden, D.W. (1994) Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis. Infect Immun 62: 5247-5254.
63. Southern, E.M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503-517.
64. Struhl, K., Brandl, C.J., Chen, W., Harbury, P.A., Hope, I.A., and Mahadevan, S. (1988) Transcriptional activation by yeast GCN4, a functional homolog to the jun oncoprotein. Cold Spring Harb Symp Quant Biol 53: 701-709.
65. Tang, C.M., Cohen, J., Krausz, T., Van Noorden, S., and Holden, D.W. (1993) The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis. Infect Immun 61: 1650-1656.
66. Tavernarakis, N., and Thireos, G. (1995) Transcriptional interference caused by GCN4 overexpression reveals multiple interactions mediating transcriptional activation. Mol Gen Genet 247: 571-578.
67. Tian, G., Lim, D., Oppenheim, J.D., and Maas, W.K. (1994) Explanation for different types of regulation of arginine biosynthesis in Escherichia coli B and Escherichia coli K12 caused by a difference between their arginine repressors. J Mol Biol 235: 221-230.
68. Tripathi, G., Wiltshire, C., Macaskill, S., Tournu, H., Budge, S., and Brown, A.J. (2002) Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans. EMBO J 21: 5448-5456.
69. Tsai, H.F., Chang, Y.C., Washburn, R.G., Wheeler, M.H., and Kwon-Chung, K.J. (1998) The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence. J Bacteriol 180: 3031-3038.
70. Tsai, H.F., Wheeler, M.H., Chang, Y.C., and Kwon-Chung, K.J. (1999) A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus. J Bacteriol 181: 6469-6477.
71. Wanke, C., Eckert, S., Albrecht, G., van Hartingsveldt, W., Punt, P.J., van den Hondel, C.A., and Braus, G.H. (1997) The Aspergillus niger GCN4 homologue, cpcA, is transcriptionally regulated and encodes an unusual leucine zipper. Mol Microbiol 23: 23-33.
72. Wek, S.A., Zhu, S., and Wek, R.C. (1995) The histidyl-tRNA synthetase-related sequence in the elF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids. Mol Cell Biol 15: 4497-4506.
73. Woodcock, D.M., Crowther, P.J., Doherty, J., Jefferson, S., DeCruz, E., Noyer-Weidner, M., et al. (1989) Quantitative evaluation of Escherichia coli host strains for tolerance to cytosine methylation in plasmid and phage recombinants. Nucleic Acids Res 17: 3469-3478.
74. Zhang, P., McGrath, B.C., Reinert, J., Olsen, D.S., Lei, L., Gill, S., et al. (2002) The GCN2 elF2alpha kinase is required for adaptation to amino acid deprivation in mice. Mol Cell Biol 22: 6681-6688.