A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus

PLoS Pathogens

Volumn 5, Issue 1, 2009, Pages

  Richie, Daryl L ^a   Hartl, Lukas ^b   Aimanianda, Vishukumar ^b   Winters, Michael S ^a   Fuller, Kevin K ^a   Miley, Michael D ^a   White, Stephanie ^a   McCarthy, Jason W ^c   Latgé, Jean Paul ^b   Feldmesser, Marta ^c   Rhodes, Judith C ^a   Askew, David S ^a  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b INSTITUT PASTEUR   (France)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ANTIFUNGAL AGENT; CASPOFUNGIN; FLUCONAZOLE; ITRACONAZOLE; PROTEINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; CELL WALL; CELLULAR STRESS RESPONSE; CONTROLLED STUDY; ENDOPLASMIC RETICULUM STRESS; ENZYME RELEASE; FEMALE; FUNGAL GENE; FUNGAL VIRULENCE; FUNGUS GROWTH; GENE DELETION; HACA GENE; HEAT TOLERANCE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN FOLDING; UNFOLDED PROTEIN RESPONSE; ANIMAL; ENDOPLASMIC RETICULUM; HOMEOSTASIS; IMMUNOLOGY; MICROBIOLOGY; PATHOGENICITY; PHYSIOLOGY; VIRULENCE;

ASPERGILLUS FUMIGATUS; FUNGI;

ANIMALS; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; ENDOPLASMIC RETICULUM; HOMEOSTASIS; MICE; PROTEIN FOLDING; VIRULENCE;

EID: 59249085255     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1000258     Document Type: Article

References (86)

1. Maschmeyer G, Haas A, Cornely OA (2007) Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs 67: 1567-1601.
2. Morgan J, Wannemuehler KA, Marr KA, Hadley S, Kontoyiannis DP, et al. (2005) Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol 43 Suppl 1: S49-58.
3. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA (2007) Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 44: 531-540.
4. Filler SG, Sheppard DC (2006) Fungal invasion of normally non-phagocytic host cells. PLoS Pathog 2: e129. doi:10.1371/journal.ppat.0020129.
5. Tekaia F, Latge JP (2005) Aspergillus fumigatus: saprophyte or pathogen? Curr Opin Microbiol 8: 385-392.
6. Wilson LS, Reyes CM, Stolpman M, Speckman J, Allen K, et al. (2002) The direct cost and incidence of systemic fungal infections. Value Health 5: 26-34.
7. Lin SJ, Schranz J, Teutsch SM (2001) Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 32: 358-366.
8. Talbot GH, Bradley J, Edwards JE Jr, Gilbert D, Scheld M, et al. (2006) Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 42: 657-668.
9. Robson GD, Huang J, Wortman J, Archer DB (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: S41-47.
10. Gifford AH, Klippenstein JR, Moore MM (2002) Serum stimulates growth of and proteinase secretion by Aspergillus fumigatus. Infect Immun 70: 19-26.
11. Berka RM, Kodama KH, Rey MW, Wilson LJ, Ward M (1991) The development of Aspergillus niger var. awamori as a host for the expression and secretion of heterologous gene products. Biochem Soc Trans 19: 681-685.
12. Dunn-Coleman NS, Bloebaum P, Berka RM, Bodie E, Robinson N, et al. (1991) Commercial levels of chymosin production by Aspergillus. Biotechnology (N Y) 9: 976-981.
13. Nyyssonen E, Penttila M, Harkki A, Saloheimo A, Knowles JK, et al. (1993) Efficient production of antibody fragments by the filamentous fungus Trichoderma reesei. Biotechnology (N Y) 11: 591-595.
14. Romanos MA, Scorer CA, Clare JJ (1992) Foreign gene expression in yeast: a review. Yeast 8: 423-488.
15. Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73: 1019-1049.
16. Schubert U, Anton LC, Gibbs J, Norbury CC, Yewdell JW, et al. (2000) Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404: 770-774.
17. Romisch K (2004) A cure for traffic jams: small molecule chaperones in the endoplasmic reticulum. Traffic 5: 815-820.
18. Malhotra JD, Kaufman RJ (2007) The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 18: 716-731.
19. Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8: 519-529.
20. Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, et al. (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101: 249-258.
21. Sidrauski C, Walter P (1997) The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 90: 1031-1039.
22. Shamu CE, Walter P (1996) Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. Embo J 15: 3028-3039.
23. Lee KP, Dey M, Neculai D, Cao C, Dever TE, et al. (2008) Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell 132: 89-100.
24. Cox JS, Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87: 391-404.
25. Kimata Y, Ishiwata-Kimata Y, Yamada S, Kohno K (2006) Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins. Genes Cells 11: 59-69.
26. Back SH, Schroder M, Lee K, Zhang K, Kaufman RJ (2005) ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Methods 35: 395-416.
27. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, et al. (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415: 92-96.
28. Wimalasena TT, Enjalbert B, Guillemette T, Plumridge A, Budge S, et al. (2008) Impact of the unfolded protein response upon genome-wide expression patterns, and the role of Hac1 in the polarized growth, of Candida albicans. Fungal Genet Biol 45: 1235-1247.
29. Saloheimo M, Valkonen M, Penttila M (2003) Activation mechanisms of the HAC1-mediated unfolded protein response in filamentous fungi. Mol Microbiol 47: 1149-1161.
30. Mulder HJ, Saloheimo M, Penttila M, Madrid SM (2004) The transcription factor HACA mediates the unfolded protein response in Aspergillus niger, and upregulates its own transcription. Mol Genet Genomics 271: 130-140.
31. Mulder HJ, Nikolaev I, Madrid SM (2006) HACA, the transcriptional activator of the unfolded protein response (UPR) in Aspergillus niger, binds to partly palindromic UPR elements of the consensus sequence 5′-CAN(G/A)NTGT/ GCCT-3′. Fungal Genet Biol 43: 560-572.
32. Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9: 2277-2293.
33. Bhabhra R, Askew DS (2005) Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 43 Suppl 1: S87-93.
34. Chang HJ, Jesch SA, Gaspar ML, Henry SA (2004) Role of the unfolded protein response pathway in secretory stress and regulation of INO1 expression in Saccharomyces cerevisiae. Genetics 168: 1899-1913.
35. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, et al. (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11: 4241-4257.
36. Ram AF, Klis FM (2006) Identification of fungal cell wall mutants using susceptibility assays based on Calcofluor white and Congo red. Nat Protoc 1: 2253-2256.
37. Lepak A, Nett J, Lincoln L, Marchillo K, Andes D (2006) Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole. Antimicrob Agents Chemother 50: 1311-1319.
38. Liu TT, Lee RE, Barker KS, Wei L, Homayouni R, et al. (2005) Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Antimicrob Agents Chemother 49: 2226-2236.
39. Agarwal AK, Rogers PD, Baerson SR, Jacob MR, Barker KS, et al. (2003) Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae. J Biol Chem 278: 34998-35015.
40. Douglas CM (2006) Understanding the microbiology of the Aspergillus cell wall and the efficacy of caspofungin. Med Mycol 44 Suppl: 95-99.
41. Brewer JW, Hendershot LM (2005) Building an antibody factory: a job for the unfolded protein response. Nat Immunol 6: 23-29.
42. Chavira R Jr, Burnett TJ, Hageman JH (1984) Assaying proteinases with azocoll. Anal Biochem 136: 446-450.
43. Rementeria A, Lopez-Molina N, Ludwig A, Vivanco AB, Bikandi J, et al. (2005) Genes and molecules involved in Aspergillus fumigatus virulence. Rev Iberoam Micol 22: 1-23.
44. Spikes S, Xu R, Nguyen CK, Chamilos G, Kontoyiannis DP, et al. (2008) Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence. J Infect Dis 197: 479-486.
45. Sugui JA, Pardo J, Chang YC, Zarember KA, Nardone G, et al. (2007) Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone. Eukaryot Cell 6: 1562-1569.
46. Stephens-Romero SD, Mednick AJ, Feldmesser M (2005) The pathogenesis of fatal outcome in murine pulmonary aspergillosis depends on the neutrophil depletion strategy. Infect Immun 73: 114-125.
47. Matsumoto R, Akama K, Rakwal R, Iwahashi H (2005) The stress response against denatured proteins in the deletion of cytosolic chaperones SSA1/2 is different from heat-shock response in Saccharomyces cerevisiae. BMC Genomics 6: 141.
48. Kasuya T, Nakajima H, Kitamoto K (1999) Cloning and characterization of the bipA gene encoding ER chaperone BiP from Aspergillus oryzae. J Biosci Bioeng 88: 472-478.
49. Holtz WA, Turetzky JM, Jong YJ, O'Malley KL (2006) Oxidative stress-triggered unfolded protein response is upstream of intrinsic cell death evoked by parkinsonian mimetics. J Neurochem 99: 54-69.
50. Yan M, Shen J, Person MD, Kuang X, Lynn WS, et al. (2008) Endoplasmic reticulum stress and unfolded protein response in Atm-deficient thymocytes and thymic lymphoma cells are attributable to oxidative stress. Neoplasia 10: 160-167.
51. Feldman DE, Chauhan V, Koong AC (2005) The unfolded protein response: a novel component of the hypoxic stress response in tumors. Mol Cancer Res 3: 597-605.
52. Koumenis C, Wouters BG (2006) "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res 4: 423-436.
53. Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, et al. (2002) The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol 3: 411-421.
54. Gass JN, Gifford NM, Brewer JW (2002) Activation of an unfolded protein response during differentiation of antibody-secreting B cells. J Biol Chem 277: 49047-49054.
55. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, et al. (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7: 1165-1176.
56. Reimold AM, Etkin A, Clauss I, Perkins A, Friend DS, et al. (2000) An essential role in liver development for transcription factor XBP-1. Genes Dev 14: 152-157.
57. Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, et al. (2003) Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol 4: 321-329.
58. Schwienbacher M, Weig M, Thies S, Regula JT, Heesemann J, et al. (2005) Analysis of the major proteins secreted by the human opportunistic pathogen Aspergillus fumigatus under in vitro conditions. Med Mycol 43: 623-630.
59. Galagan JE, Calvo SE, Cuomo C, Ma LJ, Wortman JR, et al. (2005) Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438: 1105-1115.
60. Machida M, Asai K, Sano M, Tanaka T, Kumagai T, et al. (2005) Genome sequencing and analysis of Aspergillus oryzae. Nature 438: 1157-1161.
61. Durand H (1988) Classical and molecular genetics applied to Trichoderma reesei for selection of improved cellulolytic industrial strains. In: Aubert J-P, Beguin P, Millet P, eds. Biochemistry and genetics of cellulose degradation. London: Academic Press. pp 135-152.
62. Valkonen M, Ward M, Wang H, Penttila M, Saloheimo M (2003) Improvement of foreign-protein production in Aspergillus niger var. awamori by constitutive induction of the unfolded-protein response. Appl Environ Microbiol 69: 6979-6986.
63. Dave A, Jeenes DJ, Mackenzie DA, Archer DB (2006) HacA-independent induction of chaperone-encoding gene bipA in Aspergillus niger strains overproducing membrane proteins. Appl Environ Microbiol 72: 953-955.
64. Patil CK, Li H, Walter P (2004) Gcn4p and novel upstream activating sequences regulate targets of the unfolded protein response. PLoS Biol 2: e246. doi:10.1371/journal.pbio.0020246.
65. Pakula TM, Laxell M, Huuskonen A, Uusitalo J, Saloheimo M, et al. (2003) The effects of drugs inhibiting protein secretion in the filamentous fungus Trichoderma reesei. Evidence for down-regulation of genes that encode secreted proteins in the stressed cells. J Biol Chem 278: 45011-45020.
66. Al-Sheikh H, Watson AJ, Lacey GA, Punt PJ, MacKenzie DA, et al. (2004) Endoplasmic reticulum stress leads to the selective transcriptional downregulation of the glucoamylase gene in Aspergillus niger. Mol Microbiol 53: 1731-1742.
67. Fujioka T, Mizutani O, Furukawa K, Sato N, Yoshimi A, et al. (2007) MpkA-Dependent and -independent cell wall integrity signaling in Aspergillus nidulans. Eukaryot Cell 6: 1497-1510.
68. Schmalhorst PS, Krappmann S, Vervecken W, Rohde M, Muller M, et al. (2008) Contribution of Galactofuranose to the Virulence of the Opportunistic Pathogen Aspergillus fumigatus. Eukaryot Cell 7: 1268-1277.
69. Latge JP (2007) The cell wall: a carbohydrate armour for the fungal cell. Mol Microbiol 66: 279-290.
70. Beauvais A, Bruneau JM, Mol PC, Buitrago MJ, Legrand R, et al. (2001) Glucan synthase complex of Aspergillus fumigatus. J Bacteriol 183: 2273-2279.
71. Mellado E, Dubreucq G, Mol P, Sarfati J, Paris S, et al. (2003) Cell wall biogenesis in a double chitin synthase mutant (chsG-/chsE-) of Aspergillus fumigatus. Fungal Genet Biol 38: 98-109.
72. Pfaller MA, Messer SA, Hollis RJ, Jones RN (2002) Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob Agents Chemother 46: 1032-1037.
73. Singh J, Rimek D, Kappe R (2006) Intrinsic in vitro susceptibility of primary clinical isolates of Aspergillus fumigatus, Aspergillus terreus, Aspergillus nidulans, Candida albicans and Candida lusitaniae against amphotericin B. Mycoses 49: 96-103.
74. Araujo R, Pina-Vaz C, Rodrigues AG (2007) Susceptibility of environmental versus clinical strains of pathogenic Aspergillus. Int J Antimicrob Agents 29: 108-111.
75. Lass-Florl C, Griff K, Mayr A, Petzer A, Gastl G, et al. (2005) Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. Br J Haematol 131: 201-207.
76. Spanakis EK, Aperis G, Mylonakis E (2006) New agents for the treatment of fungal infections: clinical efficacy and gaps in coverage. Clin Infect Dis 43: 1060-1068.
77. Bruno VM, Kalachikov S, Subaran R, Nobile CJ, Kyratsous C, et al. (2006) Control of the C. albicans cell wall damage response by transcriptional regulator Cas5. PLoS Pathog 2: e21. doi:10.1371/journal.ppat.0020021.
78. Reinoso-Martin C, Schuller C, Schuetzer-Muehlbauer M, Kuchler K (2003) The yeast protein kinase C cell integrity pathway mediates tolerance to the antifungal drug caspofungin through activation of Slt2p mitogen-activated protein kinase signaling. Eukaryot Cell 2: 1200-1210.
79. Wimalasena TT, Enjalbert B, Guillemette T, Plumridge A, Budge S, et al. (2008) Impact of the unfolded protein response upon genome-wide expression patterns, and the role of Hac1 in the polarized growth, of Candida albicans. Fungal Genet Biol.
80. Ibrahim-Granet O, Dubourdeau M, Latge JP, Ave P, Huerre M, et al. (2008) Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis. Cell Microbiol 10: 134-148.
81. Souza W (2006) Secretory organelles of pathogenic protozoa. An Acad Bras Cienc 78: 271-291.
82. Armstrong PB (2006) Proteases and protease inhibitors: a balance of activities in host-pathogen interaction. Immunobiology 211: 263-281.
83. Cove DJ (1966) The induction and repression of nitrate reductase in the fungus Aspergillus nidulans. Biochim Biophys Acta 113: 51-56.
84. Catlett NL, Lee B-N, Yoder OC, Turgeon BG (2002) Split-marker recombination for efficient targeted deletion of fungal genes. Fungal Genet News 50: 9-11.
85. Bhabhra R, Miley MD, Mylonakis E, Boettner D, Fortwendel J, et al. (2004) Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect Immun 72: 4731-4740.
86. Fontaine T, Simenel C, Dubreucq G, Adam O, Delepierre M, et al. (2000) Molecular organization of the alkali-insoluble fraction of Aspergillus fumigatus cell wall. J Biol Chem 275: 27594-27607.