Virulence Factors of Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells

1. Gomez MI, Prince A. Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Current opinion in pharmacology. 2007;7(3):244–51. 17418640

2. Soler N, Torres A, Ewig S, Gonzalez J, Celis R, El-Ebiary M, et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. American journal of respiratory and critical care medicine. 1998;157(5 Pt 1):1498–505. 9603129

3. Sethi S, Evans N, Grant BJ, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. The New England journal of medicine. 2002;347(7):465–71. 12181400

4. Rada B, Leto TL. Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections. Trends in microbiology. 2013;21(2):73–81. doi: 10.1016/j.tim.2012.10.004 23140890

5. Bleves S, Viarre V, Salacha R, Michel GP, Filloux A, Voulhoux R. Protein secretion systems in Pseudomonas aeruginosa: A wealth of pathogenic weapons. International journal of medical microbiology: IJMM. 2010;300(8):534–43. doi: 10.1016/j.ijmm.2010.08.005 20947426

6. Hunter RC, Klepac-Ceraj V, Lorenzi MM, Grotzinger H, Martin TR, Newman DK. Phenazine content in the cystic fibrosis respiratory tract negatively correlates with lung function and microbial complexity. American journal of respiratory cell and molecular biology. 2012;47(6):738–45. doi: 10.1165/rcmb.2012-0088OC 22865623

7. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR, D'Argenio DA, et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(22):8487–92. 16687478

8. Muller M. Premature cellular senescence induced by pyocyanin, a redox-active Pseudomonas aeruginosa toxin. Free radical biology & medicine. 2006;41(11):1670–7.

9. Wilson R, Pitt T, Taylor G, Watson D, MacDermot J, Sykes D, et al. Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. The Journal of clinical investigation. 1987;79(1):221–9. 3098783

10. Denning GM, Wollenweber LA, Railsback MA, Cox CD, Stoll LL, Britigan BE. Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infection and immunity. 1998;66(12):5777–84. 9826354

11. Denning GM, Railsback MA, Rasmussen GT, Cox CD, Britigan BE. Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells. The American journal of physiology. 1998;274(6 Pt 1):L893–900. 9609727

12. Britigan BE, Railsback MA, Cox CD. The Pseudomonas aeruginosa secretory product pyocyanin inactivates alpha1 protease inhibitor: implications for the pathogenesis of cystic fibrosis lung disease. Infection and immunity. 1999;67(3):1207–12. 10024562

13. Tamura Y, Suzuki S, Kijima M, Takahashi T, Nakamura M. Effect of proteolytic enzyme on experimental infection of mice with Pseudomonas aeruginosa. The Journal of veterinary medical science / the Japanese Society of Veterinary Science. 1992;54(3):597–9. 1643183

14. Bardoel BW, van der Ent S, Pel MJ, Tommassen J, Pieterse CM, van Kessel KP, et al. Pseudomonas evades immune recognition of flagellin in both mammals and plants. PLoS pathogens. 2011;7(8):e1002206. doi: 10.1371/journal.ppat.1002206 21901099

15. Parmely M, Gale A, Clabaugh M, Horvat R, Zhou WW. Proteolytic inactivation of cytokines by Pseudomonas aeruginosa. Infection and immunity. 1990;58(9):3009–14. 2117578

16. Hong YQ, Ghebrehiwet B. Effect of Pseudomonas aeruginosa elastase and alkaline protease on serum complement and isolated components C1q and C3. Clinical immunology and immunopathology. 1992;62(2):133–8. 1730152

17. Singh PK, Parsek MR, Greenberg EP, Welsh MJ. A component of innate immunity prevents bacterial biofilm development. Nature. 2002;417(6888):552–5. 12037568

18. O'May CY, Sanderson K, Roddam LF, Kirov SM, Reid DW. Iron-binding compounds impair Pseudomonas aeruginosa biofilm formation, especially under anaerobic conditions. Journal of medical microbiology. 2009;58(Pt 6):765–73. doi: 10.1099/jmm.0.004416-0 19429753

19. Vasil ML, Ochsner UA. The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Molecular microbiology. 1999;34(3):399–413. 10564483

20. Kim EJ, Wang W, Deckwer WD, Zeng AP. Expression of the quorum-sensing regulatory protein LasR is strongly affected by iron and oxygen concentrations in cultures of Pseudomonas aeruginosa irrespective of cell density. Microbiology (Reading, England). 2005;151(Pt 4):1127–38. 15817780

21. Marciniak SJ, Ron D. Endoplasmic reticulum stress signaling in disease. Physiological reviews. 2006;86(4):1133–49. 17015486

22. Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999;397(6716):271–4. 9930704

23. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Molecular cell. 2000;5(5):897–904. 10882126

24. Sood R, Porter AC, Ma K, Quilliam LA, Wek RC. Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress. The Biochemical journal. 2000;346 Pt 2:281–93. 10677345

25. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular cell. 2000;6(5):1099–108. 11106749

26. Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes & development. 2004;18(24):3066–77.

27. Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. The Journal of cell biology. 2001;153(5):1011–22. 11381086

28. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107(7):881–91. 11779464

29. Haze K, Yoshida H, Yanagi H, Yura T, Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Molecular biology of the cell. 1999;10(11):3787–99. 10564271

30. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, et al. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Molecular and cellular biology. 2000;20(18):6755–67. 10958673

31. Dalton LE, Healey E, Irving J, Marciniak SJ. Phosphoproteins in stress-induced disease. Progress in molecular biology and translational science. 2012;106:189–221. doi: 10.1016/B978-0-12-396456-4.00003-1 22340719

32. Clemens MJ, Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 1997;17(9):503–24.

33. Samuel CE, Kuhen KL, George CX, Ortega LG, Rende-Fournier R, Tanaka H. The PKR protein kinase--an interferon-inducible regulator of cell growth and differentiation. International journal of hematology. 1997;65(3):227–37. 9114594

34. Sood R, Porter AC, Olsen DA, Cavener DR, Wek RC. A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. Genetics. 2000;154(2):787–801. 10655230

35. Berlanga JJ, Santoyo J, De Haro C. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. European journal of biochemistry / FEBS. 1999;265(2):754–62. 10504407

36. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Molecular cell. 2003;11(3):619–33. 12667446

37. Roussel BD, Kruppa AJ, Miranda E, Crowther DC, Lomas DA, Marciniak SJ. Endoplasmic reticulum dysfunction in neurological disease. Lancet neurology. 2013;12(1):105–18. doi: 10.1016/S1474-4422(12)70238-7 23237905

38. Ribeiro CM, Paradiso AM, Schwab U, Perez-Vilar J, Jones L, O'Neal W, et al. Chronic airway infection/inflammation induces a Ca2+i-dependent hyperinflammatory response in human cystic fibrosis airway epithelia. The Journal of biological chemistry. 2005;280(18):17798–806. 15746099

39. Richardson CE, Kooistra T, Kim DH. An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature. 2010;463(7284):1092–5. doi: 10.1038/nature08762 20182512

40. Martinon F, Chen X, Lee AH, Glimcher LH. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nature immunology. 2010;11(5):411–8. doi: 10.1038/ni.1857 20351694

41. Clavarino G, Claudio N, Couderc T, Dalet A, Judith D, Camosseto V, et al. Induction of GADD34 is necessary for dsRNA-dependent interferon-beta production and participates in the control of Chikungunya virus infection. PLoS pathogens. 2012;8(5):e1002708. doi: 10.1371/journal.ppat.1002708 22615568

42. Clavarino G, Claudio N, Dalet A, Terawaki S, Couderc T, Chasson L, et al. Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(8):3006–11. doi: 10.1073/pnas.1104491109 22315398

43. Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nature cell biology. 2013;15(5):481–90. doi: 10.1038/ncb2738 23624402

44. Martino ME, Olsen JC, Fulcher NB, Wolfgang MC, O'Neal WK, Ribeiro CM. Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. The Journal of biological chemistry. 2009;284(22):14904–13. doi: 10.1074/jbc.M809180200 19321437

45. Blohmke CJ, Mayer ML, Tang AC, Hirschfeld AF, Fjell CD, Sze MA, et al. Atypical Activation of the Unfolded Protein Response in Cystic Fibrosis Airway Cells Contributes to p38 MAPK-Mediated Innate Immune Responses. Journal of immunology (Baltimore, Md: 1950). 2012;189(11):5467–75. doi: 10.4049/jimmunol.1103661 23105139

46. Liu J, Xu Y, Stoleru D, Salic A. Imaging protein synthesis in cells and tissues with an alkyne analog of puromycin. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(2):413–8. doi: 10.1073/pnas.1111561108 22160674

47. Halldorsson S, Gudjonsson T, Gottfredsson M, Singh PK, Gudmundsson GH, Baldursson O. Azithromycin maintains airway epithelial integrity during Pseudomonas aeruginosa infection. American journal of respiratory cell and molecular biology. 2010;42(1):62–8. doi: 10.1165/rcmb.2008-0357OC 19372247

48. Soong G, Parker D, Magargee M, Prince AS. The type III toxins of Pseudomonas aeruginosa disrupt epithelial barrier function. Journal of bacteriology. 2008;190(8):2814–21. doi: 10.1128/JB.01567-07 18165298

49. Vikstrom E, Tafazoli F, Magnusson KE. Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-l-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells. FEBS letters. 2006;580(30):6921–8. 17157842

50. van der Kleij D, van den Biggelaar AH, Kruize YC, Retra K, Fillie Y, Schmitz M, et al. Responses to Toll-like receptor ligands in children living in areas where schistosome infections are endemic. The Journal of infectious diseases. 2004;189(6):1044–51. 14999608

51. Wilson R, Sykes DA, Watson D, Rutman A, Taylor GW, Cole PJ. Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium. Infection and immunity. 1988;56(9):2515–7. 3137173

52. O'Malley YQ, Reszka KJ, Rasmussen GT, Abdalla MY, Denning GM, Britigan BE. The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells. American journal of physiology Lung cellular and molecular physiology. 2003;285(5):L1077–86. 12871859

53. Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxidants & redox signaling. 2007;9(12):2277–93.

54. Yates SP, Jorgensen R, Andersen GR, Merrill AR. Stealth and mimicry by deadly bacterial toxins. Trends in biochemical sciences. 2006;31(2):123–33. 16406634

55. Braun P, de Groot A, Bitter W, Tommassen J. Secretion of elastinolytic enzymes and their propeptides by Pseudomonas aeruginosa. Journal of bacteriology. 1998;180(13):3467–9. 9642203

56. Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(15):E869–78. doi: 10.1073/pnas.1115623109 22315414

57. Yang YL, Reis LF, Pavlovic J, Aguzzi A, Schafer R, Kumar A, et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. The EMBO journal. 1995;14(24):6095–106. 8557029

58. Han AP, Yu C, Lu L, Fujiwara Y, Browne C, Chin G, et al. Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. The EMBO journal. 2001;20(23):6909–18. 11726526

59. Chakrabarti S, Liehl P, Buchon N, Lemaitre B. Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut. Cell host & microbe. 2012;12(1):60–70.

60. Visca P, Imperi F, Lamont IL. Pyoverdine siderophores: from biogenesis to biosignificance. Trends in microbiology. 2007;15(1):22–30. 17118662

61. Novoa I, Zhang Y, Zeng H, Jungreis R, Harding HP, Ron D. Stress-induced gene expression requires programmed recovery from translational repression. The EMBO journal. 2003;22(5):1180–7. 12606582

62. Valentine CD, Anderson MO, Papa FR, Haggie PM. X-Box Binding Protein 1 (XBP1s) Is a Critical Determinant of Pseudomonas aeruginosa Homoserine Lactone-Mediated Apoptosis. PLoS pathogens. 2013;9(8):e1003576. doi: 10.1371/journal.ppat.1003576 23990788

63. Essar DW, Eberly L, Hadero A, Crawford IP. Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications. Journal of bacteriology. 1990;172(2):884–900. 2153661

64. Laarman AJ, Bardoel BW, Ruyken M, Fernie J, Milder FJ, van Strijp JA, et al. Pseudomonas aeruginosa alkaline protease blocks complement activation via the classical and lectin pathways. Journal of immunology (Baltimore, Md: 1950). 2012;188(1):386–93. doi: 10.4049/jimmunol.1102162 22131330

65. van Wetering S, van der Linden AC, van Sterkenburg MA, Rabe KF, Schalkwijk J, Hiemstra PS. Regulation of secretory leukocyte proteinase inhibitor (SLPI) production by human bronchial epithelial cells: increase of cell-associated SLPI by neutrophil elastase. Journal of investigative medicine: the official publication of the American Federation for Clinical Research. 2000;48(5):359–66. 10979241

66. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Molecular cell. 2001;7(6):1165–76. 11430820

67. Kumar A, Yang YL, Flati V, Der S, Kadereit S, Deb A, et al. Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB. The EMBO journal. 1997;16(2):406–16. 9029159

68. van Schadewijk A, van't Wout EF, Stolk J, Hiemstra PS. A quantitative method for detection of spliced X-box binding protein-1 (XBP1) mRNA as a measure of endoplasmic reticulum (ER) stress. Cell stress & chaperones. 2012;17(2):275–9.

69. Wegener J, Keese CR, Giaever I. Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces. Experimental cell research. 2000;259(1):158–66. 10942588

70. Haas D, Holloway BW. R factor variants with enhanced sex factor activity in Pseudomonas aeruginosa. Molecular & general genetics: MGG. 1976;144(3):243–51.

71. Scott DW, Mutamba S, Hopkins RG, Loo G. Increased GADD gene expression in human colon epithelial cells exposed to deoxycholate. Journal of cellular physiology. 2005;202(1):295–303. 15316935

72. Hirota M, Kitagaki M, Itagaki H, Aiba S. Quantitative measurement of spliced XBP1 mRNA as an indicator of endoplasmic reticulum stress. The Journal of toxicological sciences. 2006;31(2):149–56. 16772704

73. Fitch SR, Kimber GM, Wilson NK, Parker A, Mirshekar-Syahkal B, Gottgens B, et al. Signaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis. Cell stem cell. 2012;11(4):554–66. doi: 10.1016/j.stem.2012.07.002 23040481

74. Song B, Scheuner D, Ron D, Pennathur S, Kaufman RJ. Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. The Journal of clinical investigation. 2008;118(10):3378–89. doi: 10.1172/JCI34587 18776938

75. Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells. PloS one. 2008;3(2):e1648. doi: 10.1371/journal.pone.0001648 18286202