The fungal UPR: A regulatory hub for virulence traits in the mold pathogen Aspergillus fumigatus

Virulence

Volumn 5, Issue 2, 2014, Pages 334-340

  Krishnan, Karthik ^a   Askew, David S ^a  

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

Author keywords

Aspergillosis; Aspergillus fumigatus; ER stress; ERAD; Unfolded protein response; UPR; Virulence

Indexed keywords

ANTIFUNGAL AGENT; BASIC LEUCINE ZIPPER TRANSCRIPTION FACTOR; ERGOSTEROL; FUNGAL RNA;

ANTIFUNGAL ACTIVITY; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; CELL MEMBRANE; CELL WALL; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; FUNGAL GENE; FUNGAL VIRULENCE; HOMEOSTASIS; HUMAN; HYPOXIA; IRE1 GENE; NONHUMAN; REVIEW; SECRETION (PROCESS); TEMPERATURE ACCLIMATIZATION; UNFOLDED PROTEIN RESPONSE; YEAST;

ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; ER STRESS; ERAD; UNFOLDED PROTEIN RESPONSE; UPR; VIRULENCE;

ASPERGILLUS FUMIGATUS; HOST-PATHOGEN INTERACTIONS; HUMANS; STRESS, PHYSIOLOGICAL; UNFOLDED PROTEIN RESPONSE; VIRULENCE;

EID: 84897849324     PISSN: 21505594     EISSN: 21505608     Source Type: Journal    
DOI: 10.4161/viru.26571     Document Type: Review

References (60)

1. Segal BH. Aspergillosis. N Engl J Med 2009; 360:1870-84; PMID:19403905; http://dx.doi. org/10.1056/NEJMra0808853
2. Shoham S, Marr KA. Invasive fungal infections in solid organ transplant recipients. Future Microbiol 2012; 7:639-55; PMID:22568718; http://dx.doi. org/10.2217/fmb.12.28
3. Azie N, Neofytos D, Pfaller M, Meier-Kriesche HU, Quan SP, Horn D. The PATH (Prospective Antifungal Therapy) Alliance® registry and invasive fungal infections: update 2012. Diagn Microbiol Infect Dis 2012; 73:293-300; PMID:22789847; http://dx.doi. org/10.1016/j.diagmicrobio.2012.06.012
4. Hawksworth DL. Naming Aspergillus species: progress towards one name for each species. Med Mycol 2011; 49(Suppl 1):S70-6; PMID:20718610; http:// dx.doi.org/10.3109/13693786.2010.504753
5. Farnell E, Rousseau K, Thornton DJ, Bowyer P, Herrick SE. Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates. Fungal Biol 2012; 116:1003-12; PMID:22954343; http://dx.doi.org/10.1016/j. funbio.2012.07.004
6. Kim A, Nicolau DP, Kuti JL. Hospital costs and outcomes among intravenous antifungal therapies for patients with invasive aspergillosis in the United States. Mycoses 2011; 54:e301-12; PMID:20557463; http://dx.doi.org/10.1111/j.1439-0507.2010.01903.x
7. Wilson LS, Reyes CM, Stolpman M, Speckman J, Allen K, Beney J. The direct cost and incidence of systemic fungal infections. Value Health 2002; 5:26-34; PMID:11873380; http://dx.doi. org/10.1046/j.1524-4733.2002.51108.x
8. van der Linden JW, Camps SM, Kampinga GA, Arends JP, Debets-Ossenkopp YJ, Haas PJ, Rijnders BJ, Kuijper EJ, van Tiel FH, Varga J, et al. Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles. Clin Infect Dis 2013; 57:513-20; PMID:23667263; http:// dx.doi.org/10.1093/cid/cit320
9. Galagan JE, Calvo SE, Cuomo C, Ma LJ, Wortman JR, Batzoglou S, Lee SI, Baştürkmen M, Spevak CC, Clutterbuck J, et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 2005; 438:1105-15; PMID:16372000; http://dx.doi.org/10.1038/nature04341
10. Machida M, Asai K, Sano M, Tanaka T, Kumagai T, Terai G, Kusumoto K, Arima T, Akita O, Kashiwagi Y, et al. Genome sequencing and analysis of Aspergillus oryzae. Nature 2005; 438:1157-61; PMID:16372010; http://dx.doi.org/10.1038/nature04300
11. Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, et al. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 2005; 438:1151-6; PMID:16372009; http://dx.doi.org/10.1038/nature04332
12. Su X, Schmitz G, Zhang M, Mackie RI, Cann IK. Heterologous gene expression in filamentous fungi. Adv Appl Microbiol 2012; 81:1-61; PMID:22958526; http://dx.doi.org/10.1016/ B978-0-12-394382-8.00001-0
13. McDonagh A, Fedorova ND, Crabtree J, Yu Y, Kim S, Chen D, Loss O, Cairns T, Goldman G, Armstrong-James D, et al. Sub-telomere directed gene expression during initiation of invasive aspergillosis. PLoS Pathog 2008; 4:e1000154; PMID:18787699; http:// dx.doi.org/10.1371/journal.ppat.1000154
14. Markaryan A, Morozova I, Yu H, Kolattukudy PE. Purification and characterization of an elastinolytic metalloprotease from Aspergillus fumigatus and immunoelectron microscopic evidence of secretion of this enzyme by the fungus invading the murine lung. Infect Immun 1994; 62:2149-57; PMID:8188335
15. Moutaouakil M, Monod M, Prévost MC, Bouchara JP, Paris S, Latgé JP. Identification of the 33-kDa alkaline protease of Aspergillus fumigatus in vitro and in vivo. J Med Microbiol 1993; 39:393-9; PMID:8246256; http://dx.doi.org/10.1099/00222615-39-5-393
16. Reichard U, Büttner S, Eiffert H, Staib F, Rüchel R. Purification and characterisation of an extracellular serine proteinase from Aspergillus fumigatus and its detection in tissue. J Med Microbiol 1990; 33:243-51; PMID:2258912; http://dx.doi. org/10.1099/00222615-33-4-243
17. Ibrahim-Granet O, Dubourdeau M, Latgé JP, Ave P, Huerre M, Brakhage AA, Brock M. Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis. Cell Microbiol 2008; 10:134-48; PMID:17973657
18. Li X, Gao M, Han X, Tao S, Zheng D, Cheng Y, Yu R, Han G, Schmidt M, Han L. Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus. Infect Immun 2012; 80:429-40; PMID:22083709; http://dx.doi.org/10.1128/ IAI.05830-11
19. Hartmann T, Sasse C, Schedler A, Hasenberg M, Gunzer M, Krappmann S. Shaping the fungal adaptome--stress responses of Aspergillus fumigatus. Int J Med Microbiol 2011; 301:408-16; PMID:21565548; http://dx.doi.org/10.1016/j.ijmm.2011.04.008
20. Moore KA, Hollien J. The unfolded protein response in secretory cell function. Annu Rev Genet 2012; 46:165-83; PMID:22934644; http://dx.doi. org/10.1146/annurev-genet-110711-155644
21. Korennykh A, Walter P. Structural basis of the unfolded protein response. Annu Rev Cell Dev Biol 2012; 28:251-77; PMID:23057742; http://dx.doi. org/10.1146/annurev-cellbio-101011-155826
22. Kohno K. Stress-sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals. J Biochem 2010; 147:27-33; PMID:19942680; http://dx.doi.org/10.1093/jb/ mvp196
23. Brodsky JL. Cleaning up: ER-associated degradation to the rescue. Cell 2012; 151:1163-7; PMID:23217703; http://dx.doi.org/10.1016/j. cell.2012.11.012
24. Feng X, Krishnan K, Richie DL, Aimanianda V, Hartl L, Grahl N, Powers-Fletcher MV, Zhang M, Fuller KK, Nierman WC, et al. HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS Pathog 2011; 7:e1002330; PMID:22028661; http://dx.doi.org/10.1371/journal. ppat.1002330
25. Richie DL, Hartl L, Aimanianda V, Winters MS, Fuller KK, Miley MD, White S, McCarthy JW, Latgé JP, Feldmesser M, et al. A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS Pathog 2009; 5:e1000258; PMID:19132084; http://dx.doi. org/10.1371/journal.ppat.1000258
26. Rüegsegger U, Leber JH, Walter P. Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 2001; 107:103-14; PMID:11595189; http://dx.doi.org/10.1016/ S0092-8674(01)00505-0
27. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 2002; 415:92-6; PMID:11780124; http://dx.doi. org/10.1038/415092a
28. Wimalasena TT, Enjalbert B, Guillemette T, Plumridge A, Budge S, Yin Z, Brown AJ, Archer DB. 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 2008; 45:1235-47; PMID:18602013; http://dx.doi.org/10.1016/j.fgb.2008.06.001
29. Saloheimo M, Valkonen M, Penttilä M. Activation mechanisms of the HAC1-mediated unfolded protein response in filamentous fungi. Mol Microbiol 2003; 47:1149-61; PMID:12581366; http://dx.doi. org/10.1046/j.1365-2958.2003.03363.x
30. Mulder HJ, Saloheimo M, Penttilä M, Madrid SM. The transcription factor HACA mediates the unfolded protein response in Aspergillus niger, and upregulates its own transcription. Mol Genet Genomics 2004; 271:130-40; PMID:14730445; http://dx.doi. org/10.1007/s00438-003-0965-5
31. Yanagitani K, Imagawa Y, Iwawaki T, Hosoda A, Saito M, Kimata Y, Kohno K. Cotranslational targeting of XBP1 protein to the membrane promotes cytoplasmic splicing of its own mRNA. Mol Cell 2009; 34:191-200; PMID:19394296; http://dx.doi. org/10.1016/j.molcel.2009.02.033
32. Mulder HJ, Nikolaev I. HacA-dependent transcriptional switch releases hacA mRNA from a translational block upon endoplasmic reticulum stress. Eukaryot Cell 2009; 8:665-75; PMID:19181870; http://dx.doi.org/10.1128/EC.00131-08
33. Guillemette T, van Peij N, Goosen T, Lanthaler K, Robson GD, van den Hondel CA, Stam H, Archer DB. Genomic analysis of the secretion stress response in the enzyme-producing cell factory Aspergillus niger. BMC Genomics 2007; 8:158; PMID:17561995; http://dx.doi.org/10.1186/1471-2164-8-158
34. Mulder HJ, Nikolaev I, Madrid SM. 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 2006; 43:560-72; PMID:16709461; http://dx.doi. org/10.1016/j.fgb.2006.02.005
35. Jung KW, Kang HA, Bahn YS. Essential roles of the Kar2/BiP molecular chaperone downstream of the UPR pathway in Cryptococcus neoformans. PLoS One 2013; 8:e58956; PMID:23484059; http://dx.doi. org/10.1371/journal.pone.0058956
36. Cheon SA, Jung KW, Chen YL, Heitman J, Bahn YS, Kang HA. Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog 2011; 7:e1002177; PMID:21852949; http://dx.doi.org/10.1371/journal.ppat.1002177
37. Havel VE, Wool NK, Ayad D, Downey KM, Wilson CF, Larsen P, Djordjevic JT, Panepinto JC. Ccr4 promotes resolution of the endoplasmic reticulum stress response during host temperature adaptation in Cryptococcus neoformans. Eukaryot Cell 2011; 10:895-901; PMID:21602483; http://dx.doi. org/10.1128/EC.00006-11
38. Miyazaki T, Nakayama H, Nagayoshi Y, Kakeya H, Kohno S. Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata. PLoS Pathog 2013; 9:e1003160; PMID:23382685; http://dx.doi.org/10.1371/journal. ppat.1003160
39. Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, Walter P. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 2000; 101:249-58; PMID:10847680; http://dx.doi.org/10.1016/S0092-8674(00)80835-1
40. Shen X, Ellis RE, Sakaki K, Kaufman RJ. Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet 2005; 1:e37; PMID:16184190; http://dx.doi.org/10.1371/journal. pgen.0010037
41. Hollien J, Lin JH, Li H, Stevens N, Walter P, Weissman JS. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J Cell Biol 2009; 186:323-31; PMID:19651891; http://dx.doi. org/10.1083/jcb.200903014
42. Bhabhra R, Askew DS. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 2005; 43(Suppl 1):S87-93; PMID:16110798; http://dx.doi. org/10.1080/13693780400029486
43. Richie DL, Feng X, Krishnan K, Askew DS. Secretion stress and antifungal resistance: an Achilles' heel of Aspergillus fumigatus? Med Mycol 2011; 49(Suppl 1):S101-6; PMID:20608779; http://dx.doi.org/10.3 109/13693786.2010.497504
44. Tada R, Latgé JP, Aimanianda V. Undressing the fungal cell wall/cell membrane--the antifungal drug targets. Curr Pharm Des 2013; 19:3738-47; PMID:23278542; http://dx.doi. org/10.2174/1381612811319200012
45. Sturley SL. Conservation of eukaryotic sterol homeostasis: new insights from studies in budding yeast. Biochim Biophys Acta 2000; 1529:155-63; PMID:11111085; http://dx.doi.org/10.1016/ S1388-1981(00)00145-1
46. Weinberg ED. The role of iron in protozoan and fungal infectious diseases. J Eukaryot Microbiol 1999; 46:231-8; PMID:10377984; http://dx.doi. org/10.1111/j.1550-7408.1999.tb05119.x
47. Schrettl M, Haas H. Iron homeostasis--Achilles' heel of Aspergillus fumigatus? Curr Opin Microbiol 2011; 14:400-5; PMID:21724450; http://dx.doi. org/10.1016/j.mib.2011.06.002
48. Grahl N, Shepardson KM, Chung D, Cramer RA. Hypoxia and fungal pathogenesis: to air or not to air? Eukaryot Cell 2012; 11:560-70; PMID:22447924; http://dx.doi.org/10.1128/EC.00031-12
49. Willger SD, Puttikamonkul S, Kim KH, Burritt JB, Grahl N, Metzler LJ, Barbuch R, Bard M, Lawrence CB, Cramer RA Jr. A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathog 2008; 4:e1000200; PMID:18989462; http://dx.doi. org/10.1371/journal.ppat.1000200
50. Richie DL, Feng X, Hartl L, Aimanianda V, Krishnan K, Powers-Fletcher MV, Watson DS, Galande AK, White SM, Willett T, et al. The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR). Virulence 2011; 2:12-21; PMID:21217201; http://dx.doi. org/10.4161/viru.2.1.13345
51. Krishnan K, Feng X, Powers-Fletcher MV, Bick G, Richie DL, Woollett LA, Askew DS. Effects of a defective endoplasmic reticulum-associated degradation pathway on the stress response, virulence, and antifungal drug susceptibility of the mold pathogen Aspergillus fumigatus. Eukaryot Cell 2013; 12:512-9; PMID:23355008; http://dx.doi.org/10.1128/ EC.00319-12
52. Kraskiewicz H, FitzGerald U. InterfERing with endoplasmic reticulum stress. Trends Pharmacol Sci 2012; 33:53-63; PMID:22112465; http://dx.doi. org/10.1016/j.tips.2011.10.002
53. Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, Schürer SC, Oakes SA, Papa FR, Maly DJ. Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors. Nat Chem Biol 2012; 8:982-9; PMID:23086298; http://dx.doi. org/10.1038/nchembio.1094
54. Volkmann K, Lucas JL, Vuga D, Wang X, Brumm D, Stiles C, Kriebel D, Der-Sarkissian A, Krishnan K, Schweitzer C, et al. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J Biol Chem 2011; 286:12743-55; PMID:21303903; http://dx.doi.org/10.1074/jbc.M110.199737
55. Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, Solow-Cordero DE, Bouley DM, Offner F, Niwa M, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 2011; 117:1311-4; PMID:21081713; http://dx.doi. org/10.1182/blood-2010-08-303099
56. Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, Narita T, Masaki A, Ito A, Ding J, et al. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J 2012; 2:e79; PMID:22852048; http://dx.doi. org/10.1038/bcj.2012.26
57. Thibault G, Ismail N, Ng DT. The unfolded protein response supports cellular robustness as a broad-spectrum compensatory pathway. Proc Natl Acad Sci U S A 2011; 108:20597-602; PMID:22143797; http:// dx.doi.org/10.1073/pnas.1117184109
58. Iwawaki T, Akai R, Kohno K. IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level. PLoS One 2010; 5:e13052; PMID:20885949; http://dx.doi.org/10.1371/journal. pone.0013052
59. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci U S A 2009; 106:16657-62; PMID:19805353; http://dx.doi.org/10.1073/pnas.0903775106
60. Mimura N, Fulciniti M, Gorgun G, Tai YT, Cirstea D, Santo L, Hu Y, Fabre C, Minami J, Ohguchi H, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood 2012; 119:5772-81; PMID:22538852; http:// dx.doi.org/10.1182/blood-2011-07-366633