1887

Chapter 24 : Molecular Determinants of Virulence in

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Molecular Determinants of Virulence in , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap24-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap24-2.gif

Abstract:

The opportunistic pathogen is a ubiquitous fungus that can cause diseases that range in severity from mild allergic rhinitis to life-threatening invasive pulmonary and disseminated infection. The importance of biosyntheses of primary metabolites for the growth of the fungus in host tissue has been addressed by a number of investigators. For example, -aminobenzoic acid-requiring mutants are nonpathogenic in a murine infection model of invasive pulmonary aspergillosis. Mutants of that lack a functional copy of are hypersensitive to the amino acid analog 5-methyltryptophan, which induces a starvation response in the wild type. In two different murine models, the Δ mutants display decreased virulence as measured by cumulative mortality and competitive growth. The production of elastinolytic proteinases was correlated with virulence in environmental and clinical isolates; the production of these enzymes during infection was demonstrated by detecting antibody responses to the enzymes in patients. Toxins of two classes have been studied for their contribution to the virulence of . Using the model to assay virulence, four clinical strains of and one of were compared for production of gliotoxin, growth rate, elastase and catalase activities, and virulence.

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24

Key Concept Ranking

Murine Invasive Pulmonary Aspergillosis
0.4008251
0.4008251
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1.
Figure 1.

Schematic representation of fungal DHN-melanin biosynthesis pathways (adapted from references and ). Probable reaction types are indicated ([O], oxidation; [H], reduction; –HO, dehydration). Arrows with dashed lines indicate probable reactions. CoA, coenzyme A.

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Pentaketide-like melanin biosynthesis gene cluster of Adapted from reference .

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Model of cAMP signal transduction in . Question marks indicate unverified components and reactions. Dashed arrows mark unverified relationships. Proteins deduced from cloned genes are labeled with circles shaded in gray. It is expected that cross talk between the cAMP regulatory network and other regulatory networks exists. Some of these potential interactions, which were deduced from current data, are indicated by questions marks. Adapted form reference .

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555815776.ch24
1. Arruda, L. K.,, T. A. E. Platts-Mills,, J. W. Fox, and, M. D. Chapman. 1990. Aspergillus fumigatus allergen I, a major IgE-binding protein, is a member of the mitogillin family of cytotoxins. J. Exp. Med. 172:15291532.
2. Aufauvre-Brown, A.,, J. S. Brown, and, D. W. Holden. 1998. Comparison of virulence between clinical and environmental isolates of Aspergillus fumigatus. Eur. J. Clin. Microbiol. Infect. Dis. 17:778780.
3. Aufauvre-Brown, A.,, E. Mellado,, N. A. Gow, and, D. W. Holden. 1995. A multigene family related to chitin synthase genes in yeast in the opportunistic pathogen Aspergillus fumigatus. Mol. Gen. Genet. 246:353359.
4. Aufauvre-Brown, A.,, E. Mellado,, N. A. R. Gow, and, D. W. Holden. 1997. Aspergillus fumigatus chsE : a gene related to CHS3 of Saccharomyces cerevisiae and important for hyphal growth and conidiophore development but not pathogenicity. Fungal Genet. Biol. 21:141152.
5. Balloy, V.,, M. Huerre,, J.-P. Latgé, and, M. Chignard. 2005. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect. Immun. 73:494503.
6. 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. 72:47314740.
7. Boettner, D.,, N. Huebner,, J. C. Rhodes, and, D. S. Askew. 2001. Molecular cloning of Aspergillus fumigatus cgrA, the ortholog of a conserved fungal nucleolar protein. Med. Mycol. 39:517521.
8. Bok, J. W.,, S. A. Balajee,, K. A. Marr,, D. Andes,, K. F. Nielsen,, J. C. Frisvad, and, N. P. Keller. 2005. LaeA, a regulator of morphogenetic fungal virulence factors. Eukaryot. Cell 4:15741582.
9. Bok, J. W., and, N. P. Keller. 2004. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell 3:527535.
10. Bölker, M. 1998. Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis. Fungal Genet. Biol. 25:143156.
11. Brakhage, A. A., and, K. Langfelder. 2002. Menacing mold: the molecular biology of Aspergillus fumigatus. Annu. Rev Microbiol. 56:433455.
12. Brakhage, A. A.,, K. Langfelder,, G. Wanner,, A. Schmidt, and, B. Jahn. 1999. Pigment biosynthesis and virulence. Contrib. Microbiol. 2:205215.
13. Brakhage, A. A., and, B. Liebmann. 2005. Aspergillus fumigatus conidial pigment and cAMP signal transduction: significance for virulence. Med. Mycol. 43:575582.
14. Brown, J. S.,, A. Aufauvre-Brown,, J. Brown,, J. M. Jennings,, H. Arst, and, D. W. Holden. 2000. Signature-tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity. Mol. Microbiol. 36:13711380.
15. Butler, M. J., and, A. W. Day. 1998. Fungal melanins: a review. Can. J. Microbiol. 44:11151136.
16. Calera, J. A.,, S. Paris,, M. Monod,, A. J. Hamilton,, J.-P. Debeaupuis,, M. Diaquin,, R. Lopez-Medrano,, F. Leal, and, J.-P. Latgé. 1997. Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus. Infect. Immun. 65:47184724.
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. Chazalet, V.,, J.-P. Debeaupuis,, J. Sarfati,, J. Lortholary,, P. Ribaud,, P. Shah,, M. Cornet,, H. V. Thien,, E. Gluckman,, G. Brücker, and, J-P. Latgé. 1998. Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings. J. Clin. Microbiol. 36:14941500.
19. Clemons, K. V.,, T. K. Miller,, C. P. Selitrennikoff, and, D. A. Stevens. 2002. fos-1, a putative histidine kinase as a virulence factor for systemic aspergillosis. Med. Mycol. 40:259262.
20. d’Enfert, C.,, M. Diaquin,, A. Delit,, N. Wuscher,, J. Debeaupuis,, M. Huerre, and, J. Latgé. 1996. Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus. Infect. Immun. 64:44014405.
21. Denning, D. W.,, L. Hall,, M. Jackson, and, S. Hollis. 1995. Efficacy of D0870 compared with those of intraconazole and amphotericin B in two murine models of invasive aspergillosis. Antimicrob. Agents Chemother. 39:18091814.
22. Denning, D. W.,, P. N. Ward,, L. E. Fenelon, and, E. W. Benbow. 1992. Lack of vessel wall elastinolysis in human invasive pulmonary aspergillosis. Infect. Immun. 60:51535156.
23. Diamond, R. D., and, R. A. Clark. 1982. Damage of Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. Infect. Immun. 38:487495.
24. 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.
25. D’Souza, C. A., and, J. Heitman. 2001. Conserved cAMP signaling cascades regulate fungal development and virulence. FEMS Microbiol. Rev. 25:349364.
26. Dürrenberger, F.,, K. Wong, and, J. W. Kronstad. 1998. Identification of a cAMP-dependent protein kinase catalytic subunit required for virulence and morphogenesis in Ustilago maydis. Proc. Natl. Acad. Sci. USA 95:56845689.
27. Ellis, M. 1999. Therapy of Aspergillus fumigatus-related diseases, p. 105129. In A. A. Brakhage,, B. Jahn, and, A. Schmidt (ed.), Aspergillus fumigatus: Biology, Clinical Aspects and Molecular Approaches to Pathogenicity. Karger, Basel, Switzerland.
28. Fillinger, S.,, M.-K. Chaveroche,, K. Shimizu,, N. Keller, and, C. d’Enfert. 2002. cAMP and ras signalling independently control spore germination in the filamentous fungus Aspergillus nidulans. Mol. Microbiol. 44:10011016.
29. Fortwendel, J. R.,, W. Zhao,, R. Bhabra,, S. Parks,, D. S. Perlin,, D. S. Askew, and, J. C. Rhodes. 2005. A fungus-specific ras homolog contributes to the hyphal growth and virulence of Aspergillus fumigatus. Eukaryot. Cell 4:19821989.
30. Francis, P.,, J. W. Lee,, A. Hoffman,, J. Peter,, A. Francesconi,, J. Bacher,, J. Shelhamer,, P. A. Pizzo, and, T. J. Walsh. 1994. Efficacy of unilamellar liposomal amphotericin B in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: the potential role of bronchoalveolar D-mannitol and serum galactomannan as markers of infection. J. Infect. Dis. 169:356368.
31. Fujii, I.,, Y. Yasuoka,, H.-F. Tsai,, Y. C. Chang,, K. J. Kwon-Chung, and, Y. Ebizuka. 2004. Hydrolytic polyke-tide shortening by Ayg1p, a novel enzyme involved in fungal melanin biosynthesis. J. Biol. Chem. 279:4461344620.
32. Garrad, R. C., and, J. K. Bhattacharjee. 1992. Lysine biosynthesis in selected pathogenic fungi: characterization of lysine auxotrophs and the cloned LYS1 gene of Candida albicans. J. Bacteriol. 174:73797384.
33. Goodley, J. M.,, Y. M. Clayton, and, R. J. Hay. 1994. Environmental sampling for aspergilli during building construction on a hospital site. J. Hosp. Infect. 26:2735.
34. Haase, G., and, A. A. Brakhage. 2004. Melanized fungi infecting humans, p. 6788. In J. E. Domer and, G. S. Kobayashi (ed.), Human Fungal Pathogens, vol. XII. Springer-Verlag KG, Berlin, Germany.
35. Hamilton, A. J., and, B. L. Gomez. 2002. Melanins in fungal pathogens. J. Med. Microbiol. 51:189191.
36. 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.
37. Holdom, M. D.,, R. J. Hay, and, A. J. Hamilton. 1996. The Cu,Zn superoxide dismutases of Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus: purification and biochemical comparison with the Aspergillus fumigatus Cu,Zn superoxide dismutase. Infect. Immun. 64:33263332.
38. Holdom, M. D.,, B. Lechenne,, R. J. Hay,, A. J. Hamilton, and, M. Monod. 2000. Production and characterization of recombinant Aspergillus fumigatus Cu,Zn superoxide dismutase and its recognition by immune human sera. J. Clin. Microbiol. 38:558562.
39. Hospenthal, D. R.,, K. J. Kwon-Chung, and, J. E. Bennett. 1998. Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. Med. Mycol. 36:165168.
40. Ibrahim-Granet, O., and, C. D’Enfert. 1997. The Aspergillus fumigatus mepB gene encodes an 82 kDa intracellular metalloproteinase structurally related to mammalian thimet oligopeptidases. Microbiology 143:22472253.
41. Jacobson, E. S. 2000. Pathogenic roles for fungal melanins. Clin. Microbiol. Rev. 13:708717.
42. Jahn, B.,, F. Boukhallouk,, J. Lotz,, K. Langfelder,, G. Wanner, and, A. A. Brakhage. 2000. Interaction of human phagocytes with pigmentless Aspergillus conidia. Infect. Immun. 68:37363739.
43. Jahn, B.,, A. Koch,, A. Schmidt,, G. Wanner,, H. Gehringer,, S. Bhakdi, and, A. A. Brakhage. 1997. Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect. Immun. 65:51105117.
44. Jahn, B.,, K. Langfelder,, U. Schneider,, C. Schindel, and, A. A. Brakhage. 2002. PKSP-dependent reduction of phagolysosome fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell. Microbiol. 4:793803.
45. Jahn, B.,, A. Stueben, and, S. Bhakdi. 1996. Colorimetric susceptibility testing of Aspergillus fumigatus: comparison of menandione-augmented 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and alamar blue tests. J. Clin. Microbiol. 34:20392041.
46. Jaton-Ogay, K.,, S. Paris,, M. Huerre,, M. Quadroni,, R. Falchetto,, G. Togni,, J.-P. Latgé, and, M. Monod. 1994. Cloning and disruption of the gene encoding an extracellular metalloprotease of Aspergillus fumigatus. Mol. Microbiol. 14:917928.
47. Kolattukudy, P. E.,, J. D. Lee,, L. M. Rogers,, P. Zimmerman,, S. Ceselski,, B. Fox,, B. Stein, and, E. A. Copelan. 1993. Evidence for possible involvement of an elastinolytic serine protease in aspergillosis. Infect. Immun. 61:23572368.
48. Kothary, M. H.,, J. T. Chase, and, J. D. Macmillan. 1984. Correlation of elastase production by some strains of Aspergillus fumigatus with ability to cause pulmonary invasive aspergillosis in mice. Infect. Immun. 43:320325.
49. 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.
50. Kronstad, J.,, D. DeMaria,, D. Funnell,, R. D. Laidlaw,, N. Lee,, M. deSa, and, M. Ramesh. 1998. Signaling via cAMP in fungi: interconnections with mitogen-activated protein kinase pathways. Arch. Microbiol. 170:395404.
51. Lamy, B.,, M. Moutaouakil,, J.-P. Latgé, and, J. Davies. 1991. Secretion of a potential virulence factor, a fungal ribonucleotoxin, during human aspergillosis infections. Mol. Microbiol. 5:18111815.
52. Langfelder, K.,, B. Jahn,, H. Gehringer,, A. Schmidt,, G. Wanner, and, A. A. Brakhage. 1998. Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence. Med. Microbiol. Immunol. 187:7989.
53. Langfelder, K.,, B. Philippe,, B. Jahn,, J.-P. Latgé, and, A. A. Brakhage. 2001. Differential expression of the Aspergillus fumigatus pksP gene detected in vitro and in vivo with green fluorescent protein. Infect. Immun. 69:64116418.
54. Langfelder, K.,, M. Streibel,, B. Jahn,, G. Haase, and, A. A. Brakhage. 2003. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal. Genet. Biol. 38:143158.
55. Latgé, J.-P. 1999. Aspergillus fumigatus and aspergillosis. Clin. Microbiol. Rev. 12:310350.
56. Lee, J. D., and, P. E. Kolattukudy. 1995. Molecular cloning of the cDNA and gene for an elastinolytic aspartic proteinse from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung. Infect. Immun. 63:37963803.
57. Lengeler, K. B.,, R. C. Davidson,, C. D’Souza,, T. Harashima,, W.-C. Shen,, P. Wang,, X. Pan,, M. Waugh, and, J. Heitman. 2000. Signal transduction cascades regulating fungal development and virulence. Microbiol. Mol. Biol. Rev. 64:746785.
58. Levitz, S. M., and, R. D. Diamond. 1985. A rapid colori-metric assay of fungal viability with tetrazolium salt MTT. J. Infect. Dis. 152:938945.
59. Levitz, S. M., and, T. P. Farrell. 1990. Human neutrophil degranulation stimulated by Aspergillus fumigatus. J. Leukoc. Biol. 47:170175.
60. Lewis, R. E.,, N. P. Wiederhold,, J. Chi,, X. Y. Han,, K. V. Komanduri,, D. P. Kontoyiannis, and, R. A. Prince. 2005. Detection of gliotoxin in experimental and human aspergillosis. Infect. Immun. 73:635637.
61. 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. Genomics 269:420435.
62. Liebmann, B.,, T. W. Mühleisen,, M. Müller,, M. Hecht,, G. Weidner,, A. Braun,, M. Brock, and, A. A. Brakhage. 2004. 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.
63. Liebmann, B.,, M. Müller,, A. Braun, and, A. A. Brakhage. 2004. The cyclic AMP-dependent protein kinase A network regulates development and virulence in Aspergillus fumigatus. Infect. Immun. 72:51935203.
64. Manning, M.,, C. B. Snoddy, and, R. A. Fromtling. 1984. Comparative pathogenicity of auxotrophic mutants of Candida albicans. Can. J. Microbiol. 30:3135.
65. Markaryan, A.,, I. Morozova,, H. Yu, and, P. E. Kolattukudy. 1994. Purification and characterization of an elastinolytic metalloproteinse from Aspergillus fumigatus and immunoelectron microscopic evidence of secretion of this enzyme by the fungus invading the murine lung. Infect. Immun. 62:21492157.
66. Mehrad, B.,, R. M. Strieter,, T. A. Moore,, W. C. Tsai,, S. A. Lira, and, T. J. Standiford. 1999. CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis. J. Immunol. 163:60866094.
67. Mellado, E.,, A. Aufauvre-Brown,, N. A. Gow, and, D. W. Holden. 1996. The Aspergillus fumigatus chsC and chsG genes encode class III chitin synthases with different functions. Mol. Microbiol. 20:667679.
68. Mellado, E.,, G. Dubreucq,, P. Mol,, J. Sarfati,, S. Paris,, M. Diaquin,, D. W. Holden,, J. L. Rodriguez-Tudela, and, J. P. Latgé. 2003. Cell wall biogenesis in a double chitin synthase mutant (chsG /chsE) of Aspergillus fumigatus. Fungal Genet. Biol. 38:98109.
69. Mellado, E.,, C. A. Specht,, P. W. Robbins, and, D. W. Holden. 1996. Cloning and characterization of chsD, a chitin synthase-like gene of Aspergillus fumigatus. FEMS Microbiol. Lett. 143:6976.
70. Meshulam, T.,, S. M. Levitz,, L. Christin, and, R. D. Diamond. 1995. A simplified new assay for assessment of fungal cell damage with the tetrazolium dye, (2,3)-bis-(2-methoxy-4-nitro-5-sulphenyl)-(2H)-tetrazolium-5-carboxyanilide (XTT). J. Infect. Dis. 172:11531156.
71. Monod, M.,, K. Jaton-Ogay, and, U. Reichard. 1999. Aspergillus fumigatus-secreted proteases as antigenic factors and virulence factors., p. 182192. In A. A. Brakhage,, B. Jahn, and, A. Schmidt (ed.), Aspergillus fumigatus. Biology, Clinical Aspects and Molecular Approaches to Pathogenicity, vol. 2. Karger, Basel, Switzerland.
72. Monod, M.,, S. Paris,, J. Sarfati,, K. Jaton-Ogay,, P. Ave, and, J.-P. Latgé. 1993. Virulence of alkaline protease-deficient mutants of Aspergillus fumigatus. FEMS Microbiol. Lett. 106:3946.
73. Moser, M.,, G. Menz,, K. Blaser, and, R. Crameri. 1994. Recombinant expression and antigenic properties of a 32-kilodalton extracellular alkaline protease, representing a possible vilulence factor from Aspergillus fumigatus. Infect. Immun. 62:936942.
74. 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 ribo-some subunit synthesis. Microbiology 148:10811090.
75. Mullbacher, A., and, R. D. Eichner. 1984. Immuno-suppression in vitro by a metabolite of a human pathogenic fungus. Proc. Natl. Acad. Sci. USA 81:38353837.
76. Mullbacher, A.,, P. Waring, and, R. D. Eichner. 1985. Identification of an agent in culture of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro. J. Gen. Microbiol. 131:12511258.
77. Nierman, W. C.,, G. S. May,, H. S. Kim,, M. J. Anderson,, D. Chen, and, D. W. Henning. 2005. What the Aspergillus genomes have told us. Med. Mycol. 43:S3S5.
78. 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.
79. Panepinto, J. C.,, B. G. Oliver,, T. W. Amlung,, D. S. Askew, and, J. C. Rhodes. 2002. Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation. Fungal Genet. Biol. 36:207214.
80. 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.
81. Paris, S.,, M. Monod,, M. Diaquin,, B. Lamy,, L. K. Arruda,, P. J. Punt, and, J.-P. Latgé. 1993. A transformant of Aspergillus fumigatus deficient in the antigenic cytotoxin ASPF1. FEMS Microbiol. Lett. 111:3136.
82. 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.
83. 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.
84. Philippe, B.,, O. Ibrahim-Granet,, M. C. Prévost,, M. A. Gougerot-Pocodalo,, M. S. Perez,, A. VanderMeeren, and, J. P. Latgé. 2003. Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect. Immun. 71:30343042.
85. Reeves, E. P.,, C. G. M. Messina,, S. Doyle, and, K. Kavanagh. 2004. Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella. Mycopathologia 158:7379.
86. Reichard, U.,, S. Büttner,, H. Eiffert,, F. Staib, and, R. Rüchel. 1990. Purification and characterisation of an extracellular serine proteinase from Aspergillus fumigatus and its detection in tissue. J. Med. Microbiol. 33:243251.
87. Reichard, U.,, M. Monod,, F. Odds, and, R. Rüchel. 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. 35:189196.
88. Rhodes, J. C.,, R. B. Bode, and, C. M. McCuan-Kirsch. 1988. Elastase production in clinical isolates of Aspergillus. Diagn. Microbiol. Infect. Dis. 10:165170.
89. Richard, J. L., and, M. C. DeBey. 1995. Production of gliotoxin during the pathogenic state in turkey poults by Aspergillus fumigatus Fresenius. Mycopathologia 129:111115.
90. Roncero, C. 2002. The genetic complexity of chitin synthesis in fungi. Curr. Genet. 41:367378.
91. Rüchel, R., and, U. Reichard. 1999. Pathogenesis and clinical presentation of aspergillosis, p. 143. In A. A. Brakhage,, B. Jahn, and, A. Schmidt (ed.), Aspergillus fumigatus: Biology, Clinical Aspects and Molecular Approaches to Pathogenicity. Karger, Basel, Switzerland.
92. Sakemi, S.,, T. Inagaki, and, K. Kaneda. 2000. CJ-12,371 and CJ-12,372, two novel DNA gyrase inhibitors. Fermentation, isolation, structural elucidation and biological activities. J. Antibiot. 48:134142.
93. Sandhu, D. K.,, R. S. Sandhu,, Z. U. Khan, and, V. N. Damodaran. 1976. Conditional virulence of a p-aminobenzoic acid requiring mutant of Aspergillus fumigatus. Infect. Immun. 13:527532.
94. Sarfati, J.,, M. Diaquin,, J. P. Debeaupuis,, A. Schmidt,, D. Lecaque,, A. Beauvais, and, J. P. Latgé. 2002. A new experimental murine aspergillosis model to identify strains of Aspergillus fumigatus with reduced virulence. Jpn. J. Med. Mycol. 43:203213.
95. Schaffner, A.,, C. E. Davis,, T. Schaffner,, M. Markert,, H. Douglas, and, A. I. Braude. 1986. In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism. J. Clin. Investig. 78:511524.
96. Shankar, J.,, S. Nigam,, S. Saxena,, T. Madan, and, P. U. Sarma. 2004. Identification and assignment of function to the genes of Aspergillus fumigatus expressed at 37°C. J. Eukaryot. Microbiol. 51:428432.
97. Shepherd, M. G. 1985. Pathogenicity of morphological and auxotrophic mutants of Candida albicans in experimental infections. Infect. Immun. 50:541544.
98. Sheppard, D. C.,, G. Rieg,, L. Y. Chiang,, S. G. Filler,, J. E. Edwards, Jr., and, A. S. Ibrahim. 2004. Novel inhalational murine model of invasive pulmonary aspergillosis. Antimicrob. Agents Chemother. 48:19081911.
99. Shibuya, K.,, M. Takaoka,, K. Uchida,, M. Wakayama,, H. Yamaguchi,, K. Takahashi,, S. Paris,, J.-P. Latgé, and, S. Naoe. 1999. Histopathology of experimental invasive pulmonary aspergillosis in rats: pathological comparison of pulmonary lesions induced by specific virulent factor deficient mutants. Microb. Pathog. 27:123131.
100. Shimizu, K., and, N. P. Keller. 2001. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics 157:591600.
101. Smith, J. M.,, J. E. Davies, and, D. W. Holden. 1993. Construction and pathogenicity of Aspergillus fumigatus mutants that do not produce the ribotoxin restrictocin. Mol. Microbiol. 9:10711077.
102. Smith, J. M.,, C. M. Tang,, S. VanNoorden, and, D. W. Holden. 1994. Virulence of Aspergillus fumigatus double mutants lacking restrictocin and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis. Infect. Immun. 62:52475254.
103. Štaudohar, M.,, M. Benčina,, P. van deVondervoort,, H. Panneman,, M. Legiša,, J. Visser, and, G. Ruijter. 2002. Cyclic AMP-dependent protein kinase is involved in morphogenesis in Aspergillus niger. Microbiology 148:26352645.
104. Steinbach, W. J.,, J. D. K. Benjamin,, S. A. Trasi,, J. L. Miller,, W. A. Schell,, A. K. Zaas,, W. M. Foster, and, J. R. Perfect. 2004. Value of an inhalational model of invasive aspergillosis. Med. Mycol. 42:417425.
105. Stephens-Romero, S. D.,, A. J. Mednick, and, M. Feldmesser. 2005. The pathogenesis of fatal outcome in murine pulmonary aspergillosis depends on the neutrophil depletion strategy. Infect. Immun. 73:114125.
106. Takasuka, T.,, N. M. Sayers,, M. J. Anderson,, E. W. Benbow, and, D. W. Denning. 1999. Aspergillus fumigatus catalases: cloning of an Aspergillus nidulans homologue and evidence for at least three catalases. FEMS Immunol. Med. Microbiol. 23:125133.
107. Tang, C. M.,, J. Cohen,, T. Krausz,, S. VanNoorden, and, D. W. Holden. 1993. The alkaline protease of Aspergillus fumigatus is not a virulence factor in two murine models of invasive pulmonary aspergillosis. Infect. Immun. 61:16501656.
108. Tang, C. M.,, J. M. Smith,, J. H. N. Arst, and, D. W. Holden. 1994. Virulence studies of Aspergillus nidulans mutants requiring lysine or p-benzoic acid in invasive pulmonary aspergillosis. Infect. Immun. 62:52555260.
109. Tsai, H.-F.,, Y. C. Chang,, R. G. Washburn,, M. H. Wheeler, and, K. J. Kwon-Chung. 1998. The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence. J. Bacteriol. 180:30313038.
110. Tsai, H.-F.,, I. Fujii,, A. Watanabe,, M. H. Wheeler,, Y. C. Chang,, Y. Yasuoka,, Y. Ebizuka, and, K. J. Kwon-Chung. 2001. Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptake-tide precursor. J. Biol. Chem. 276:2929229298.
111. Tsai, H.-F.,, R. G. Washburn,, Y. C. Chang, and, K. J. Kwon-Chung. 1997. Aspergillus fumigatus arp1 modulates conidial pigment and complement deposition. Mol. Microbiol. 26:175183.
112. Tsai, H.-F.,, M. H. Wheeler,, Y. C. Chang, and, K. J. Kwon-Chung. 1999. A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus. J. Bacteriol. 181:64696477.
113. Weidner, G.,, C. d’Enfert,, A. Koch,, P. C. Mol, and, A. A. Brakhage. 1998. Development of a homologous transformation system for the human pathogenic fungus Aspergillus fumigatus based on the pyrG gene encoding orotidine 5’-monophosphate decarboxylase. Curr. Genet. 33:378385.
114. Weidner, G.,, B. Steffan, and, A. A. Brakhage. 1997. The Aspergillus nidulans lysF gene encodes homoaconitase, an enzyme involved in the fungus-specific lysine biosynthesis pathway. Mol. Gen. Genet. 255:237247.
115. Wheeler, M. H., and, A. A. Bell. 1988. Melanins and their importance in pathogenic fungi, p. 338387. In M. M. McGinnis (ed.), Current Topics in Medical Mycology, vol. 2. Springer-Verlag, Inc., New York, N.Y.
116. Xue, T.,, C. K. Nguyen,, A. Romans, and, G. S. May. 2004. A mitogen-activated protein kinase that senses nitrogen regulates conidial germination and growth in Aspergillus fumigatus. Eukaryot. Cell 3:557560.

Tables

Generic image for table
Table 1.

gene deletion or disruption mutants reported to show a decrease in virulence

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error