Chapter 16 : : Survival and Death under Stress

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This chapter summarizes some of the remarkable attributes of the fungus that are important for survival in the environment and highlights their potential for overlapping functions in the host. As a thermotolerant fungus, is well-equipped for growth on diverse substrates throughout the compost cycle, including the thermophilic phase. In , two of the signaling pathways that are involved in nitrogen and carbon sensing are the Rheb/TOR and protein kinase A (PKA) pathways. The ability of to thrive on decaying plant and animal debris requires an enzymatic machinery that can efficiently degrade this material into component molecules. This must be accomplished in the presence of numerous other microorganisms that are also competing for access to the same substrates, making nutrient limitation an important stress encountered by in nature. Transcription factors such as Skn7 and AfYap1 are downstream effectors of oxidative stress response pathways, resulting in the enhanced expression of antioxidant defenses. Programmed cell death (PCD) is a mechanism of cell removal that eliminates excess or damaged cells and is a universally conserved stress response among metazoans. Organisms with increasing complexity have multiple caspase members, two of which have been identified in the genome, and . These metacaspases are required for the externalization of phosphatidylserine that occurs during stationary phase stress in , suggesting that this well-known marker of apoptotic death is metacaspase dependent in .

Citation: Askew D, Rhodes J. 2009. : Survival and Death under Stress, p 201-213. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch16

Key Concept Ranking

Programmed Cell Death
Reactive Oxygen Species
Aspergillus fumigatus
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Figure 1.

The PCD machinery in . In higher eukaryotes, two types of PCD have been described: type I (caspase dependent) and type II (autophagy dependent). Current evidence suggests that the metacaspases have a prosurvival function that is active under conditions of ER stress. Autophagy also provides a survival advantage when is under stress, allowing for conidiophore development when external nitrogen sources are limiting, as well as providing a mechanism to fuel the foraging of hyphae into unexplored substrate. Each of these functions is likely to play an important role in the survival of the fungus in the competitive environment of compost. However, it remains to be determined whether these functions also have death-promoting activities under certain other conditions.

Citation: Askew D, Rhodes J. 2009. : Survival and Death under Stress, p 201-213. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch16
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1. Adams, T. H.,, J. K. Wieser, and, J.-H. Yu. 1998. Asexual sporulation in Aspergillus nidulans. Microbiol. Mol. Biol. Rev. 62:3554.
2. Araujo, R., and, A. G. Rodrigues. 2004. Variability of germinative potential among pathogenic species of Aspergillus. J. Clin. Microbiol. 42:43354337.
3. Aravind, L.,, V. M. Dixit, and, E. V. Koonin. 2001. Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291:12791279.
4. Arsham, A. M., and, T. P. Neufeld. 2006. Thinking globally and acting locally with TOR. Curr. Opin. Cell Biol. 18:589589.
5. Aspuria, P.-J., and, F. Tamanoi. 2004. The Rheb family of GTP-binding proteins. Cell. Signal. 16:11051105.
6. Beffa, T.,, F. Staib,, J. Lott Fischer,, P. F. Lyon,, P. Gumowski,, O. E. Marfenina,, S. Dunoyer-Geindre,, F. Georgen,, R. Roch-Susuki,, L. Gallaz, and, J. P. Latgé. 1998. Mycological control and surveillance of biological waste and compost. Med. Mycol. 36 (Suppl. 1):137145.
7. Bencina, M.,, H. Panneman,, G. Ruijter,, M. Legisa, and, J. Visser. 1997. Characterization and overexpression of the Aspergillus niger gene encoding the cAMP-dependent protein kinase catalytic subunit. Microbiology 143:12111211.
8. Besteiro, S.,, R. A. Williams,, L. S. Morrison,, G. H. Coombs, and, J. C. Mottram. 2006. Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major. J. Biol. Chem. 281:1138411384.
9. Bettiga, M.,, L. Calzari,, I. Orlandi,, L. Alberghina, and, M. Vai. 2004. Involvement of the yeast metacaspase Yca1 in ubp 10Δ-programmed cell death. FEMS Yeast Res. 5:141141.
10. Bhabhra, R., and, D. S. Askew. 2005. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med. Mycol. 43 (Suppl. 1):S87S93.
11. Bhabhra, R.,, M. D. Miley,, E. Mylonakis,, D. Boettner,, J. Fortwendel,, J. C. Panepinto,, M. Postow,, J. C. Rhodes, and, D. S. Askew. 2004. Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect. Immun. 72:47314731.
12. Bhabhra, R.,, D. Richie,, H. Kim,, W. Nierman,, J. Fortwendel,, J. Aris,, J. Rhodes, and, D. Askew. 2008. Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus. Eukaryot. Cell 7:575575.
13. Brakhage, A. A., and, B. Liebmann. 2005. Aspergillus fumigatus conidial pigment and cAMP signal transduction: significance for virulence. Med. Mycol. 43 (Suppl. 1):7582.
14. Brown, J. S.,, A. Aufauvre-Brown,, J. Brown,, J. M. Jennings,, H. Arst, Jr., and, D. W. Holden. 2000. Signature-tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity. Mol. Microbiol. 36:13711380.
15. Bursch, W. 2001. The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ. 8:569581.
16. Casadevall, A., and, L. Pirofski. 2007. Accidental virulence, cryptic pathogenesis, Martians, lost hosts, and the pathogenicity of environmental microbes. Eukaryot. Cell 6:21692174.
17. Chang, Y. C.,, H. F. Tsai,, M. Karos, and, K. J. Kwon-Chung. 2004. THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet. Biol. 41:888896.
18. Chauhan, N.,, J.-P. Latgé, and, R. Calderone. 2006. Signalling and ox-idant adaptation in Candida albicans and Aspergillus fumigatus. Nat. Rev. Microbiol. 4:435444.
19. Cheng, J.,, T. S. Park,, L. C. Chio,, A. S. Fischl, and, X. S. Ye. 2003. Induction of apoptosis by sphingoid long-chain bases in Aspergillus nidulans. Mol. Cell. Biol. 23:163177.
20. Colledge, M., and, J. D. Scott. 1999. AKAPs: from structure to function. Trends Cell. Biol. 9:216221.
21. de Bertoldi, M.,, G. Vallini, and, A. Pera. 1983. The biology of composting: a review. Waste Manage. Res. 1:157176.
22. Dementhon, K.,, M. Paoletti,, B. Pinan-Lucarre,, N. Loubradou-Bourges,, M. Sabourin,, S. J. Saupe, and, C. Clave. 2003. Rapamycin mimics the incompatibility reaction in the fungus Podospora anser-ina. Eukaryot. Cell 2:238246.
23. Dementhon, K.,, S. J. Saupe, and, C. Clave. 2004. Characterization of IDI-4, a bZIP transcription factor inducing autophagy and cell death in the fungus Podospora anserina. Mol. Microbiol. 53:16251640.
24. D’Enfert, C.,, M. Diaquin,, A. Delit,, N. Wuscher,, J. P. Debeaupuis,, M. Huerre, and, J. P. Latgé. 1996. Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus. Infect. Immun. 64:44014405.
25. D’Souza, C.,, J. Alspaugh,, C. Yue,, T. Harashima,, G. Cox,, J. Perfect, and, J. Heitman. 2001. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol. 21:31793191.
26. Ehrenshaft, M.,, A. E. Jenns,, K. R. Chung, and, M. E. Daub. 1998. SOR1, a gene required for photosensitizer and singlet oxygen resistance in Cercospora fungi, is highly conserved in divergent organisms. Mol. Cell 1:603609.
27. Elmore, S. 2007. Apoptosis: a review of programmed cell death. Tox-icol. Pathol. 35:495516.
28. Epstein, E. 1997. The Science of Composting. Technomic Publishing, Lancaster, PA.
29. Ernst, J. F., and, S. K.-H. Prill. 2001. O-glycosylation. Med. Mycol. 39 (Suppl. 1):6774.
30. Fabrizio, P.,, L. Battistella,, R. Vardavas,, C. Gattazzo,, L. L. Liou,, A. Diaspro,, J. W. Dossen,, E. B. Gralla, and, V. D. Longo. 2004. Superoxide is a mediator of an altruistic aging program in Saccharo-myces cerevisiae. J. Cell Biol. 166:10551067.
31. Fahrenkrog, B.,, U. Sauder, and, U. Aebi. 2004. The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis. J. Cell Sci. 117:115126.
32. Fedorova, N. D.,, J. H. Badger,, G. D. Robson,, J. R. Wortman, and, W. C. Nierman. 2005. Comparative analysis of programmed cell death pathways in filamentous fungi. BMC Genomics 6:177.
33. Fernandez-Luna, J. L. 2007. Apoptosis regulators as targets for cancer therapy. Clin. Transl. Oncol. 9:555562.
34. Fitzgibbon, G. J.,, I. Y. Morozov,, M. G. Jones, and, M. X. Caddick. 2005. Genetic analysis of the TOR pathway in Aspergillus nidulans. Eukaryot. Cell 4:15951598.
35. Flower, T. R.,, L. S. Chesnokova,, C. A. Froelich,, C. Dixon, and, S. N. Witt. 2005. Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson’s disease. J. Mol. Biol. 351:10811100.
36. Frohlich, K. U.,, H. Fussi, and, C. Ruckenstuhl. 2007. Yeast apoptosis: from genes to pathways. Semin. Cancer Biol. 17:112121.
37. Fulda, S. 2007. Inhibitor of apoptosis proteins as targets for anticancer therapy. Expert Rev. Anticancer Ther. 7:12551264.
38. Galluzzi, L.,, M. C. Maiuri,, I. Vitale,, H. Zischka,, M. Castedo,, L. Zitvogel, and, G. Kroemer. 2007. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 14:12371243.
39. Garrido, C., and, G. Kroemer. 2004. Life’s smile, death’s grin: vital functions of apoptosis-executing proteins. Curr. Opin. Cell Biol. 16:639646.
40. Glass, N. L., and, K. Dementhon. 2006. Non-self recognition and programmed cell death in filamentous fungi. Curr. Opin. Microbiol. 9:553558.
41. Gophna, U., and, E. Z. Ron. 2003. Virulence and the heat shock response. Int. J. Med. Microbiol. 292:453461.
42. Gradisnik-Grapulin, M., and M. Legisa. 1997. A spontaneous change in the cAMP level in Aspergillus niger is influenced by the sucrose concentration and light. Appl. Environ. Microbiol. 63:28442849.
43. Greenbaum, D.,, C. Colangelo,, K. Williams, and, M. Gerstein. 2003. Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol. 4:117.
44. Griffioen, G., and, J. M. Thevelein. 2002. Molecular mechanisms controlling the localisation of protein kinase A. Curr. Genet. 41:199207.
45. Gygi, S. P.,, Y. Rochon,, B. R. Franza, and, R. Aebersold. 1999. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19:17201730.
46. Hamilton, A. J.,, M. D. Holdom, and, L. Jeavons. 1996. Expression of the Cu, Zn superoxide dismutase of Aspergillus fumigatus as determined by immunochemistry and immunoelectron microscopy. FEMS Immunol. Med. Microbiol. 14:95102.
47. Hauptmann, P.,, C. Riel,, L. A. Kunz-Schughart,, K. U. Frohlich,, F. Madeo, and, L. Lehle. 2006. Defects in N-glycosylation induce apoptosis in yeast. Mol. Microbiol. 59:765778.
48. Hensel, M.,, H. N. Arst, Jr.,, A. Aufauvre-Brown, and, D. W. Holden. 1998. The role of the Aspergillus fumigatus areA gene in invasive pulmonary aspergillosis. Mol. Gen. Genet. 258:553557.
49. Herker, E.,, H. Jungwirth,, K. A. Lehmann,, C. Maldener,, K. U. Froh-lich,, S. Wissing,, S. Buttner,, M. Fehr,, S. Sigrist, and, F. Madeo. 2004. Chronological aging leads to apoptosis in yeast. J. Cell Biol. 164:501507.
50. Hissen, A. H.,, A. N. Wan,, M. L. Warwas,, L. J. Pinto, and, M. M. Moore. 2005. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect. Immun. 73:54935503.
51. Hoffmann, B.,, O. Valerius,, M. Andermann, and, G. H. Braus. 2001. Transcriptional autoregulation and inhibition of mRNA translation of amino acid regulator gene cpcA of filamentous fungus Aspergillus nidulans. Mol. Biol. Cell 12:28462857.
52. Ibrahim-Granet, O.,, M. Dubourdeau,, J. P. Latgé,, P. Ave,, M. Huerre,, A. A. Brakhage, and, M. Brock. 2008. Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis. Cell. Microbiol. 10:134148.
53. Jacobson, E. S. 2000. Pathogenic roles for fungal melanins. Clin. Microbiol. Rev. 13:708717.
54. Jahn, B.,, K. Langfelder,, U. Schneider,, C. Schindel, and, A. A. Brak-hage. 2002. PKSP-dependent reduction of phagolysosomal fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell. Microbiol. 4:793803.
55. Jana, S., and, J. Paliwal. 2007. Apoptosis: potential therapeutic targets for new drug discovery. Curr. Med. Chem. 14:23692379.
56. Khan, M. A.,, P. B. Chock, and, E. R. Stadtman. 2005. Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 102:1732617331.
57. Klionsky, D. J. 2007. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol. 8:931937.
58. Konkel, M. E., and, K. Tilly. 2000. Temperature-regulated expression of bacterial virulence genes. Microbes Infect. 2:157166.
59. Krappmann, S.,, E. M. Bignell,, U. Reichard,, T. Rogers,, K. Haynes, and, G. H. Braus. 2004. The Aspergillus fumigatus transcriptional activator CpcA contributes significantly to the virulence of this fungal pathogen. Mol. Microbiol. 52:785799.
60. Lamarre, C.,, O. Ibrahim-Granet,, C. Du,, R. Calderone, and, J.-P. Latgé. 2007. Characterization of the SKN7 ortholog of Aspergillus fumigatus. Fungal Genet. Biol. 44:682690.
61. Latgé, J.-P. 1999. Aspergillus fumigatus and aspergillosis. Clin. Micro-biol. Rev. 12:310350.
62. Leiter, E.,, H. Szappanos,, C. Oberparleiter,, L. Kaiserer,, L. Csernoch,, T. Pusztahelyi,, T. Emri,, I. Pocsi,, W. Salvenmoser, and, F. Marx. 2005. Antifungal protein PAF severely affects the integrity of the plasma membrane of Aspergillus nidulans and induces an apoptosis-like phenotype. Antimicrob. Agents Chemother. 49:24452453.
63. Lessing, F.,, O. Kniemeyer,, I. Wozniok,, J. Loeffler,, O. Kurzai,, A. Haertl, and, A. A. Brakhage. 2007. The Aspergillus fumigatus tran-scriptional 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 6:22902302.
64. Liebmann, B.,, S. Gattung,, B. Jahn, and, A. A. Brakhage. 2003. cAMP signaling in Aspergillus fumigatus is involved in the regulation of the virulence gene pksP and in defense against macrophage killing by macrophages. Mol. Genet. Genom. 269:420435.
65. Liebmann, B.,, T. W. Mühleisen,, M. Muller,, M. Hecht,, G. Weidner,, A. Braun,, M. Brock, and, A. A. Brakhage. 2004a. Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose model mouse infection model of invasive aspergillosis. Arch. Microbiol. 181:378383.
66. Liebmann, B.,, M. Muller,, A. Braun, and, A. A. Brakhage. 2004b. The cyclic AMP-dependent protein kinase A network regulates development and virulence in Aspergillus fumigatus. Infect. Immun. 72:51935203.
67. Liu, X.-H.,, J.-P. Lu,, L. Zhang,, B. Dong,, H. Min, and, F.-C. Lin. 2007. Involvement of a Magnaporthe grisea serine/threonine kinase gene, MgATG1, in appressorium turgor and pathogenesis. Eukaryot. Cell 6:9971005.
68. Mach, K. E.,, K. A. Furge, and, C. F. Albright. 2000. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics 155:611622.
69. Machida, M.,, K. Asai,, M. Sano,, T. Tanaka,, T. Kumagai,, G. Terai,, K. Kusumoto,, T. Arima,, O. Akita,, Y. Kashiwagi,, K. Abe,, K. Gomi,, H. Horiuchi,, K. Kitamoto,, T. Kobayashi,, M. Takeuchi,, D. W. Denning,, J. E. Galagan,, W. C. Nierman,, J. Yu,, D. B. Archer,, J. W. Bennett,, D. Bhatnagar,, T. E. Cleveland,, N. D. Fedorova,, O. Gotoh,, H. Horikawa,, A. Hosoyama,, M. Ichinomiya,, R. Igarashi,, K. Iwash-ita,, P. R. Juvvadi,, M. Kato,, Y. Kato,, T. Kin,, A. Kokubun,, H. Maeda,, N. Maeyama,, J. Maruyama,, H. Nagasaki,, T. Nakajima,, K. Oda,, K. Okada,, I. Paulsen,, K. Sakamoto,, T. Sawano,, M. Taka-hashi,, K. Takase,, Y. Terabayashi,, J. R. Wortman,, O. Yamada,, Y. Yamagata,, H. Anazawa,, Y. Hata,, Y. Koide,, T. Komori,, Y. Koy-ama,, T. Minetoki,, S. Suharnan,, A. Tanaka,, K. Isono,, S. Kuhara,, N. Ogasawara, and, H. Kikuchi. 2005. Genome sequencing and analysis of Aspergillus oryzae. Nature 438:11571161.
70. Madeo, F.,, E. Herker,, C. Maldener,, S. Wissing,, S. Lachelt,, M. Herlan,, M. Fehr,, K. Lauber,, S. J. Sigrist,, S. Wesselborg, and, K. U. Frohlich. 2002. A caspase-related protease regulates apoptosis in yeast. Mol. Cell 9:911911.
71. Maerker, C,, M. Rohde,, A. A. Brakhage, and, M. Brock. 2005. Meth-ylcitrate synthase from Aspergillus fumigatus. Propionyl-CoA affects polyketide synthesis, growth and morphology of conidia. FEBS J. 272:36153615.
72. Maeta, K.,, S. Izawa, and, Y. Inoue. 2005. Methylglyoxal, a metabolite derived from glycolysis, functions as a signal initiator of the high osmolarity glycerol-mitogen-activated protein kinase cascade and calcineurin/Crz1-mediated pathway in Saccharomyces cerevisiae. J. Biol. Chem. 280:253253.
73. Maiuri,, M. C,, E. Zalckvar,, A. Kimchi, and, G. Kroemer. 2007. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8:741741.
74. Martin, D., and, M. N. Hall. 2005. The expanding TOR signaling network. Curr. Opin. Cell Biol. 17:158158.
75. Mazzoni, C,, E. Herker,, V. Palermo,, H. Jungwirth,, T. Eisenberg,, F. Madeo, and, C. Falcone. 2005. Yeast caspase 1 links messenger RNA stability to apoptosis in yeast. EMBO Rep. 6:10761076.
76. Meijer, H. A., and, A. A. Thomas. 2002. Control of eukaryotic protein synthesis by upstream open reading frames in the 5′-untranslated region of an mRNA. Biochem. J. 367:11.
77. Meijer, W. H.,, I. J. van der Klei,, M. Veenhuis, and, J. A. Kiel. 2007. ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy 3:106106.
78. Mignone, F.,, C. Gissi,, S. Liuni, and, G. Pesole. 2002. Untranslated regions of mRNAs. Genome Biol. 3: reviews0004.0001-0004.0010.
79. Mizushima, N. 2007. Autophagy: process and function. Genes Dev. 21:28612861.
80. Moreno, M. A.,, O. Ibrahim-Granet,, R. Vicentefranqueira,, J. Amich,, P. Ave,, F. Leal,, J. P. Latgé, and, J. A. Calera. 2007. The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. Mol. Microbiol. 64:11821182.
81. Mousavi, S. A., and, G. D. Robson. 2003. Entry into the stationary phase is associated with a rapid loss of viability and an apoptotic-like phenotype in the opportunistic pathogen Aspergillus fumigatus. Fungal Genet. Biol. 39:221221.
82. Mousavi, S. A., and, G. D. Robson. 2004. Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype. Microbiology 150:19371937.
83. Moy, T. I.,, D. Boettner,, J. C. Rhodes,, P. A. Silver, and, D. S. Askew. 2002. Identification of a role for Saccharomyces cerevisiae Cgr1p in pre-rRNA processing and 60S ribosome subunit synthesis. Microbiology 148:10811081.
84. Moye-Rowley, W. S. 2003. Regulation of the transcriptional response to oxidative stress in fungi: similarities and differences. Eukaryot. Cell 2:381381.
85. Ng, T. T.,, G. D. Robson, and, D. W. Denning. 1994. Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 140:24752475.
86. Ni, W.,, S. Rierson,, J. Seo, and, J. Yu. 2005. The pkaB gene encoding the secondary protein kinase A catalytic subunit has a synthetic lethal interaction with pkaA and plays overlapping and opposite roles in Aspergillus nidulans. Eukaryot. Cell 4:14651465.
87. Nierman, W. C,, A. Pain,, M. J. Anderson,, J. R. Wortman,, H. S. Kim,, J. Arroyo,, M. Berriman,, K. Abe,, D. B. Archer,, C. Bermejo,, J. Bennett,, P. Bowyer,, D. Chen,, M. Collins,, R. Coulsen,, R. Davies,, P. S. Dyer,, M. Farman,, N. Fedorova,, T. V. Feldblyum,, R. Fischer,, N. Fosker,, A. Fraser,, J. L. Garcia,, M. J. Garcia,, A. Goble,, G. H. Goldman,, K. Gomi,, S. Griffith-Jones,, R. Gwilliam,, B. Haas,, H. Haas,, D. Harris,, H. Horiuchi,, J. Huang,, S. Humphray,, J. Jimenez,, N. Keller,, H. Khouri,, K. Kitamoto,, T. Kobayashi,, S. Konzack,, R. Kulkarni,, T. Kumagai,, A. Lafon,, J. P. Latgé,, W. Li,, A. Lord,, C. Lu,, W. H. Majoros,, G. S. May,, B. L. Miller,, Y. Mohamoud,, M. Molina,, M. Monod,, I. Mouyna,, S. Mulligan,, L. Murphy,, S. O’Neil,, I. Paulsen,, M. A. Penalva,, M. Pertea,, C. Price,, B. L. Pritchard,, M. A. Quail,, E. Rabbinowitsch,, N. Rawlins,, M. A. Rajandream,, U. Reichard,, H. Renauld,, G. D. Robson,, S. Rodriguez de Cordoba,, J. M. Rodriguez-Pena,, C. M. Ronning,, S. Rutter,, S. L. Salzberg,, M. Sanchez,, J. C. Sanchez-Ferrero,, D. Saunders,, K. Seeger,, R. Squares,, S. Squares,, M. Takeuchi,, F. Tekaia,, G. Turner,, C. R. Vazquez de Aldana,, J. Weidman,, O. White,, J. Woodward,, J. H. Yu,, C. Fraser,, J. E. Galagan,, K. Asai,, M. Machida,, N. Hall,, B. Barrell, and, D. W. Denning. 2005. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438:11511156.
88. Oliver, B. G.,, J. C. Panepinto,, D. S. Askew, and, J. C. Rhodes. 2002. cAMP alteration of growth rate of Aspergillus fumigatus and Aspergillus niger is carbon-source dependent. Microbiology 148:26272633.
89. Oliver, B. G.,, J. C. Panepinto,, J. R. Fortwendel,, D. L. Smith,, D. S. Askew, and, J. C. Rhodes. 2001. Cloning and expression of pkaC and pkaR, the genes encoding the cAMP-dependent protein kinase of Aspergillus fumigatus. Mycopathologia 154:8591.
90. Paisley, D.,, G. D. Robson, and, D. W. Denning. 2005. Correlation between in vitro growth rate and in vivo virulence in Aspergillus fumigatus. Med. Mycol. 43:397401.
91. Panepinto, J. C.,, B. G. Oliver,, T. W. Amlung,, D. S. Askew, and, J. C. Rhodes. 2002. Expression of the Aspergillus fumigatus rheb homo-logue, rhbA, is induced by nitrogen starvation. Fungal Genet. Biol. 36:207214.
92. Panepinto, J. C.,, B. G. Oliver,, J. R. Fortwendel,, D. L. H. Smith,, D. S. Askew, and, J. C. Rhodes. 2003. Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein RhbA reduces virulence in a model of invasive pulmonary aspergillosis. Infect. Immun. 71:28192826.
93. Paris, S.,, D. Wysong,, J.-P. Debeaupuis,, K. Shibuya,, B. Philippe,, R. D. Diamond, and, J.-P. Latgé. 2003. Catalases of Aspergillus fumigatus. Infect. Immun. 71:35513562.
94. Patel, P. H.,, N. Thapar,, L. Guo,, M. Martinez,, J. Maris,, C.-L. Gau,, J. A. Lengyei, and, F. Tamanoi. 2003. Drosophila Rheb GTPase is required for cell cycle progression and cell growth. J. Cell Sci. 116:36013610.
95. Paul, A.,, S. Hackbarth,, R. D. Vogt,, B. Roder,, B. K. Burnison, and, C. E. Steinberg. 2004. Photogeneration of singlet oxygen by humic substances: comparison of humic substances of aquatic and terrestrial origin. Photochem. Photobiol. Sci. 3:273280.
96. Pinan-Lucarre, B.,, M. Paoletti, and, C. Clave. 2007. Cell death by incompatibility in the fungus Podospora. Semin. Cancer Biol. 17:101111.
97. Pinan-Lucarre, B.,, M. Paoletti,, K. Dementhon,, B. Coulary-Salin, and, C. Clave. 2003. Autophagy is induced during cell death by incompatibility and is essential for differentiation in the filamentous fungus Podospora anserina. Mol. Microbiol. 47:321333.
98. Reiter, J.,, E. Herker,, F. Madeo, and, M. J. Schmitt. 2005. Viral killer toxins induce caspase-mediated apoptosis in yeast. J. Cell Biol. 168:353358.
99. Reuther, G. W., and, C. J. Der. 2000. The Ras branch of small GTPases: Ras family members don’t fall far from the tree. Curr. Opin. Cell Biol. 12:157165.
100. Rhodes, J. C.,, B. G. Oliver,, D. S. Askew, and, T. W. Amlung. 2001. Identification of genes of Aspergillus fumigatus up-regulated during growth on endothelial cells. Med. Mycol. 39:253260.
101. Richie, D., and, D. Askew. 2007. Autophagy: a role in metal ion ho-meostasis? Autophagy 4:115117.
102. Richie, D.,, K. Fuller,, J. Fortwendel,, M. Miley,, J. McCarthy,, M. Feld-messer,, J. Rhodes, and, D. Askew. 2007a. Unexpected link between metal ion deficiency and autophagy in Aspergillus fumigatus. Eukar-yot. Cell 6:24372447.
103. Richie, D.,, M. Miley,, R. Bhabhra,, G. Robson,, J. Rhodes, and, D. Askew. 2007b. The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under conditions of endoplasmic reticulum stress. Mol. Microbiol. 63:591604.
104. Robson, G. 1999. Hyphal cell biology, p. 164184. In R. Oliver and, M. Schweizer (ed.), Molecular Fungal Biology. Cambridge University Press, Oxford, United Kingdom.
105. Robson, G. D.,, J. Huang,, J. Wortman, and, D. B. Archer. 2005. A preliminary analysis of the process of protein secretion and the diversity of putative secreted hydrolases encoded in Aspergillus fumigatus: insights from the genome. Med. Mycol. 43 (Suppl. 1):S41S47.
106. Roze, L. V., and, J. E. Linz. 1998. Lovastatin triggers an apoptosis-like cell death process in the fungus Mucor racemosus. Fungal Genet. Biol. 25:119133.
107. Schmelzle, T., and, M. N. Hall. 2000. TOR, a central controller of cell growth. Cell 103:253262.
108. Schrettl, M.,, E. Bignell,, C. Kragl,, Y. Sabiha,, O. Loss,, M. Eisendle,, A. Wallner,, H. N. Arst, Jr.,, K. Haynes, and, H. Haas. 2007. Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog. 3:11951207.
109. Schwerk, C., and, K. Schulze-Osthoff. 2003. Non-apoptotic functions of caspases in cellular proliferation and differentiation. Biochem. Pharmacol. 66:14531458.
110. Searle, J., and, Y. Sanchez. 2004. Stopped for repairs: a new role for nutrient sensing pathways. Cell Cycle 3:865868.
111. Semighini, C. P.,, J. M. Hornby,, R. Dumitru,, K. W. Nickerson, and, S. D. Harris. 2006. Farnesol-induced apoptosis in Aspergillus ni-dulans reveals a possible mechanism for antagonistic interactions between fungi. Mol. Microbiol. 59:753764.
112. Silva, R. D.,, R. Sotoca,, B. Johansson,, P. Ludovico,, F. Sansonetty,, M. T. Silva,, J. M. Peinado, and, M. Corte-Real. 2005. Hyperosmotic stress induces metacaspase- and mitochondria-dependent apoptosis in Saccharomyces cerevisiae. Mol. Microbiol. 58:824834.
113. Tansey, M. R., and, T. D. Brock. 1972. The upper temperature limit for eukaryotic organisms. Proc. Natl. Acad. Sci. USA 69:24262428.
114. Tekaia, F., and, J. P. Latgé. 2005. Aspergillus fumigatus: saprophyte or pathogen? Curr. Opin. Microbiol. 8:385392.
115. Thevelein, J. M.,, L. Cauwenberg,, S. Colombo,, J. H. DeWinde,, M. Donation,, F. Dumortier,, L. Kraakman,, K. Lemaire,, P. Ma,, D. Nau-welaers,, F. Rolland,, A. Teunissen,, P. Van Dijck,, M. Versele,, S. Wera, and, J. Winderickx. 2000. Nutrient-induced signal transduc-tion through the protein kinase A pathway and its role in the control of metabolism, stress resistance, and growth in yeast. Enzyme Microb. Technol. 26:819825.
116. Thon, M.,, Q. Al-Abdallah,, P. Hortschansky, and, A. A. Brakhage. 2007. The thioredoxin system of the filamentous fungus Aspergillus nidulans: impact on development and oxidative stress response. J. Biol. Chem. 282:2725927269.
117. Trautmann, N. M.,, T. Richard, and, M. E. Krasny. 2003. Monitoring Compost pH. Cornell University Composting Resources, Ithaca, NY.
118. Urano, J.,, A. P. Tabancay,, W. Yang, and, F. Tamanoi. 2000. The Saccharomyces cerevisiae Rheb G-protein is involved in regulating canavanine resistance and arginine uptake. J. Biol. Chem. 275:1119811206.
119. Uren, A. G.,, K. O’Rourke,, L. A. Aravind,, M. T. Pisabarro,, S. Sesh-agiri,, E. V. Koonin, and, V. M. Dixit. 2000. Identification of para-caspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol. Cell 6:961967.
120. Uritani, M.,, H. Hidaka,, Y. Hotta,, M. Ueno,, T. Ushimaru, and, T. Toda. 2006. Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase. Genes Cells 11:13671379.
121. Vachova, L., and, Z. Palkova. 2005. Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia. J. Cell Biol. 169:711717.
122. Valiante, V.,, T. Heinekamp,, R. Jain,, A. Hard, and, A. A. Brakhage. 2008. The mitogen-activated protein kinase MpkA of Aspergillus fumigatus regulates cell wall signaling and oxidative stress response. Fungal Genet. Biol. 45:618618.
123. van den Brink, J. M.,, P. J. Punt,, R. F. van Gorcom, and, C. A. van den Hondel. 2000. Regulation of expression of the Aspergillus niger benzoate para-hydroxylase cytochrome P450 system. Mol. Gen. Genet. 263:601601.
124. Veneault-Fourrey, C,, M. Barooah,, M. Egan,, G. Wakley, and, N. J. Talbot. 2006. Autophagic fungal cell death is necessary for infection by the rice blast fungus. Science 312:580580.
125. Vilela, C,, B. Linz,, C. Rodrigues-Pousada, and, J. E. McCarthy. 1998. The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 26:11501150.
126. Vilela, C, and, J. E. McCarthy. 2003. Regulation of fungal gene expression via short open reading frames in the mRNA 5′ untranslated region. Mol. Microbiol. 49:859859.
127. Vinck, A.,, M. Terlou,, W. R. Pestman,, E. P. Martens,, A. F. Ram,, C. A. van den Hondel, and, H. A. Wosten. 2005. Hyphal differentiation in the exploring mycelium of Aspergillus niger. Mol. Microbiol. 58:693699.
128. Wadskog, I.,, C. Maldener,, A. Proksch,, F. Madeo, and, L. Adler. 2004. Yeast lacking the SRO7/SOP1-encoded tumor suppressor homo-logue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress. Mol. Biol. Cell 15:14361436.
129. Washburn, M. P.,, A. Roller,, G. Oshiro,, R. R. Ulaszek,, D. Plouffe,, C. Deciu,, E. Winzeler, and, J. R. Yates III. 2003. Protein pathway and complex clustering of correlated mRNA and protein expression analyses in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 100:31073107.
130. Weinberger, M.,, L. Ramachandran,, L. Feng,, K. Sharma,, X. Sun,, M. Marchetti,, J. A. Huberman, and, W. C. Burhans. 2005. Apoptosis in budding yeast caused by defects in initiation of DNA replication. J. Cell Sci. 118:35433553.
131. Weisman, R.,, I. Roitburg,, M. Schonbrun,, R. Harari, and, M. Kupiec. 2007. Opposite effects of Tor1 and Tor2 on nitrogen starvation responses in fission yeast. Genetics 175:11531162.
132. Wilson, W. A., and, P. J. Roach. 2002. Nutrient-regulated protein ki-nases in budding yeast. Cell 111:155158.
133. Wissing, S.,, P. Ludovico,, E. Herker,, S. Buttner,, S. M. Engelhardt,, T. Decker,, A. Link,, A. Proksch,, F. Rodrigues,, M. Corte-Real,, K. U. Frohlich,, J. Manns,, C. Cande,, S. J. Sigrist,, G. Kroemer, and, F. Madeo. 2004. An AIF orthologue regulates apoptosis in yeast. J. Cell Biol. 166:969974.
134. Wullschleger, S.,, R. Loewith, and, M. N. Hall. 2006. TOR signaling growth and metabolism. Cell 124:471484.
135. Wysocki, R., and, S. J. Kron. 2004. Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J. Cell Biol. 166:311316.
136. Xie, Z., and, D. J. Klionsky. 2007. Autophagosome formation: core machinery and adaptations. Nat. Cell Biol. 9:11021109.
137. Zeuner, A.,, A. Eramo,, C. Peschle, and, R. De Maria. 1999. Caspase activation without death. Cell Death Differ. 6:10751080.
138. Zhang, L.,, M. Wang,, R. Lui, and, R. Calderone. 2005. Expression of Aspergillus fumigatus virulence-related genes detected in vitro and in vivo with competitive RT-PCR. Mycopathologia 160:201206.
139. Zhao, W.,, J. Panepinto,, J. Fortwendel,, L. Fox,, B. Oliver,, D. Askew, and, J. Rhodes. 2006. Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence. Infect. Immun. 74:48654874.
140. Zhou, H.,, H. Hu,, L. Zhang,, R. Li,, H. Ouyang,, J. Ming, and, C. Jin. 2007. O-Mannosyltransferase 1 in Aspergillus fumigatus (AfPmt1p) is crucial for cell wall integrity and conidium morphology, especially at an elevated temperature. Eukaryot. Cell 6:22602268.

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