Cystic fibrosis–adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses

Science Advances

Volumn 1, Issue 6, 2015, Pages

  LaFayette, Shantelle L ^a   Houle, Daniel ^b   Beaudoin, Trevor ^b   Wojewodka, Gabriella ^b   Radzioch, Danuta ^b   Hoffman, Lucas R ^c,d   Burns, Jane L ^d   Dandekar, Ajai A ^c   Smalley, Nicole E ^c   Chandler, Josephine R ^e   Zlosnik, James E ^f   Speert, David P ^f   Bernier, Joanie ^g   Matouk, Elias ^g   Brochiero, Emmanuelle ^h   Rousseau, Simon ^b   Nguyen, Dao ^a,b,g  

^a MCGILL UNIVERSITY   (Canada)

^b RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^c UNIVERSITY OF WASHINGTON   (United States)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF KANSAS   (United States)

^f UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^g MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^h CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIA; BIOLOGICAL ORGANS; PULMONARY DISEASES;

ADAPTIVE MUTATION; CHRONIC AIRWAY INFECTION; CHRONIC LUNG DISEASE; HYPERINFLAMMATORY RESPONSE; INFLAMMATORY RESPONSE; PRO-INFLAMMATORY CYTOKINES; PSEUDOMONAS AERUGINOSA; PULMONARY INFECTIONS;

PATHOLOGY;

EID: 84991740729     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.1500199     Document Type: Article

References (109)

1. R. L. Gibson, J. L. Burns, B. W. Ramsey, Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Resp. Crit. Care Med. 168, 918–951 (2003).
2. T. S. Cohen, A. Prince, Cystic fibrosis: A mucosal immunodeficiency syndrome. Nat. Med. 18, 509–519 (2012).
3. A. Folkesson, L. Jelsbak, L. Yang, H. K. Johansen, O. Ciofu, N. Høiby, S. Molin, Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: An evolutionary perspective. Nat. Rev. Microbiol. 10, 841–851 (2012).
4. R. L. Marvig, L. M. Sommer, S. Molin, H. K. Johansen, Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis. Nat. Genet. 47, 57–64 (2015).
5. L. Yang, L. Jelsbak, R. L. Marvig, S. Damkiær, C. T. Workman, M. H. Rau, S. K. Hansen, A. Folkesson, H. K. Johansen, O. Ciofu, N. Hoiiby, M. O. A. Sommer, S. Molin, Evolutionary dynamics of bacteria in a human host environment. Proc. Natl. Acad. Sci. U.S.A. 108, 7481–7486 (2011).
6. D. Nguyen, P. K. Singh, Evolving stealth: Genetic adaptation of Pseudomonas aeruginosa during cystic fibrosis infections. Proc. Natl. Acad. Sci. U.S.A. 103, 8305–8306 (2006).
7. A. Bragonzi, M. Paroni, A. Nonis, N. Cramer, S. Montanari, J. Rejman, C. Di Serio, G. Doring, B. Tummler, Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am. J. Resp. Crit. Care Med. 180, 138–145 (2009).
8. E. E. Smith, D. G. Buckley, Z. Wu, C. Saenphimmachak, L. R. Hoffman, D. A. D’Argenio, S. I. Miller, B. W. Ramsey, D. P. Speert, S. M. Moskowitz, J. L. Burns, R. Kaul, M. V. Olson, Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. U.S.A. 103, 8487–8492 (2006).
9. L. Yang, L. Jelsbak, S. Molin, Microbial ecology and adaptation in cystic fibrosis airways. Environ. Microbiol. 13, 1682–1689 (2011).
10. N. I. Lorè, C. Cigana, I. De Fino, C. Riva, M. Juhas, S. Schwager, L. Eberl, A. Bragonzi, Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts. PLOS One 7, e35648 (2012).
11. M. Schuster, D. J. Sexton, S. P. Diggle, E. P. Greenberg, Acyl-homoserine lactone quorum sensing: From evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).
12. M. Schuster, C. P. Lostroh, T. Ogi, E. P. Greenberg, Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: A transcriptome analysis. J. Bacteriol. 185, 2066–2079 (2003).
13. K. M. Sandoz, S. M. Mitzimberg, M. Schuster, Social cheating in Pseudomonas aeruginosa quorum sensing. Proc. Natl. Acad. Sci. U.S.A. 104, 15876–15881 (2007).
14. A. M. Luján, A. J. Moyano, I. Segura, C. E. Argaraña, A. M. Smania, Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain. Microbiology 153, 225–237 (2007).
15. S. K. Hansen, M. H. Rau, H. K. Johansen, O. Ciofu, L. Jelsbak, L. Yang, A. Folkesson, H. O. Jarmer, K. Aanaes, C. von Buchwald, N. Høiby, S. Molin, Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection. The ISME journal 6, 31–45 (2012).
16. T. Köhler, A. Buckling, C. v. Delden, Cooperation and virulence of clinical Pseudomonas aeruginosa populations. Proc. Natl. Acad. Sci. U.S.A. 106, 6339–6344 (2009).
17. L. R. Hoffman, H. D. Kulasekara, J. Emerson, L. S. Houston, J. L. Burns, B. W. Ramsey, S. I. Miller, Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J. Cyst. Fibros. 8, 66–70 (2009).
18. N. Jiricny, S. Molin, K. Foster, S. P. Diggle, P. D. Scanlan, M. Ghoul, H. K. Johansen, L. A. Santorelli, R. Popat, S. A. West, A. S. Griffin, Loss of social behaviours in populations of Pseudomonas aeruginosa infecting lungs of patients with cystic fibrosis. PLOS One 9, e83124 (2014).
19. E. Lelong, A. Marchetti, M. Simon, J. L. Burns, C. van Delden, T. K∂hler, P. Cosson, Evolution of Pseudomonas aeruginosa virulence in infected patients revealed in a Dictyostelium discoideum host model. Clin. Microbiol. Infect. 17, 1415–1420 (2011).
20. P. Lesprit, F. Faurisson, O. Join-Lambert, F. Roudot-Thoraval, M. Foglino, C. Vissuzaine, C. Carbon, Role of the quorum-sensing System in experimental pneumonia due to Pseudomonas aeruginosa in rats. Am. J. Resp. Crit. Care Med. 167, 1478–1482 (2003).
21. J. L. Burns, R. L. Gibson, S. McNamara, D. Yim, J. Emerson, M. Rosenfeld, P. Hiatt, K. McCoy, R. Castile, A. L. Smith, B. W. Ramsey, Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J. Infect. Dis. 183, 444–452 (2001).
22. P. K. Singh, A. L. Schaefer, M. R. Parsek, T. O. Moninger, M. J. Welsh, E. P. Greenberg, Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407, 762–764 (2000).
23. J. A. Bartlett, A. J. Fischer, P. B. McCray Jr., Innate immune functions of the airway epithelium. Contrib. Microbiol. 15, 147–163 (2008).
24. L. D. Martin, L. G. Rochelle, B. M. Fischer, T. M. Krunkosky, K. B. Adler, Airway epithelium as an effector of inflammation: Molecular regulation of secondary mediators. Eur. Respir. J. 10, 2139–2146 (1997).
25. A. M. Hajjar, H. Harowicz, H. D. Liggitt, P. J. Fink, C. B. Wilson, S. J. Skerrett, An essential role for non-bone marrow-derived cells in control of Pseudomonas aeruginosa pneumonia. Am. J. Respir. Cell Mol. Biol. 33, 470–475 (2005).
26. D. Parker, A. Prince, Innate immunity in the respiratory epithelium. Am. J. Respir. Cell Mol. Biol. 45, 189–201 (2011).
27. B. J. Staudinger, J. F. Muller, S. Halldorsson, B. Boles, A. Angermeyer, D. Nguyen, H. Rosen, O. Baldursson, M. Gottfreethsson, G. H. Guethmundsson, P. K. Singh, Conditions associated with the cystic fibrosis defect promote chronic Pseudomonas aeruginosa infection. Am. J. Resp. Crit. Care Med. 189, 812–824 (2014).
28. K. L. Palmer, L. M. Aye, M. Whiteley, Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J. Bacteriol. 189, 8079–8087 (2007).
29. E. DiMango, H. J. Zar, R. Bryan, A. Prince, Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J. Clin. Invest. 96, 2204–2210 (1995).
30. M. N. Becker, M. S. Sauer, M. S. Muhlebach, A. J. Hirsh, Q. Wu, M. W. Verghese, S. H. Randell, Cytokine secretion by cystic fibrosis airway epithelial cells. Am. J. Resp. Crit. Care Med. 169, 645–653 (2004).
31. E. Bruscia, F. Sangiuolo, P. Sinibaldi, K. K. Goncz, G. Novelli, D. C. Gruenert, Isolation of CF cell lines corrected at DF508-CFTR locus by SFHR-mediated targeting. Gene Ther. 9, 683–685 (2002).
32. C. Guilbault, P. Martin, D. Houle, M. L. Boghdady, M. C. Guiot, D. Marion, D. Radzioch, Cystic fibrosis lung disease following infection with Pseudomonas aeruginosa in Cftr knockout mice using novel non-invasive direct pulmonary infection technique. Lab. Anim. 39, 336–352 (2005).
33. N. Hoffmann, T. B. Rasmussen, P. ò. Jensen, C. Stub, M. Hentzer, S. r. Molin, O. Ciofu, M. Givskov, H. K. Johansen, N. Høiby, Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect. Immun. 73, 2504–2514 (2005).
34. S. Chugani, B. S. Kim, S. Phattarasukol, M. J. Brittnacher, S. H. Choi, C. S. Harwood, E. P. Greenberg, Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon. Proc. Natl. Acad. Sci. U.S.A. 109, E2823–E2831 (2012).
35. M. J. Preston, S. M. Fleiszig, T. S. Zaidi, J. B. Goldberg, V. D. Shortridge, M. L. Vasil, G. B. Pier, Rapid and sensitive method for evaluating Pseudomonas aeruginosa virulence factors during corneal infections in mice. Infect. Immun. 63, 3497–3501 (1995).
36. D. A. D’Argenio, M. Wu, L. R. Hoffman, H. D. Kulasekara, E. Deziel, E. E. Smith, H. Nguyen, R. K. Ernst, T. J. Larson Freeman, D. H. Spencer, M. Brittnacher, H. S. Hayden, S. Selgrade, M. Klausen, D. R. Goodlett, J. L. Burns, B. W. Ramsey, S. I. Miller, Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol. Microbiol. 64, 512–533 (2007).
37. N. Mayer-Hamblett, M. Rosenfeld, R. L. Gibson, B. W. Ramsey, H. D. Kulasekara, G. Z. Retsch-Bogart, W. Morgan, D. J. Wolter, C. E. Pope, L. S. Houston, B. R. Kulasekara, U. Khan, J. L. Burns, S. I. Miller, L. R. Hoffman, Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes. Am. J. Resp. Crit. Care Med. 190, 289–297 (2014).
38. P. Tingpej, L. Smith, B. Rose, H. Zhu, T. Conibear, K. A. Nassafi, J. Manos, M. Elkins, P. Bye, M. Willcox, S. Bell, C. Wainwright, C. Harbour, Phenotypic characterization of clonal and nonclonal Pseudomonas aeruginosa strains isolated from lungs of adults with cystic fibrosis. J. Clin. Microbiol. 45, 1697–1704 (2007).
39. K. J. Leavell, M. W. Peterson, T. J. Gross, Human neutrophil elastase abolishes interleukin-8 chemotactic activity. J. Leukoc. Biol. 61, 361–366 (1997).
40. U. Bank, B. Kupper, S. Ansorge, Inactivation of interleukin-6 by neutrophil proteases at sites of inflammation. Protective effects of soluble IL-6 receptor chains. Adv. Exp. Med. Biol. 477, 431–437 (2000).
41. S. D. Sagel, B. D. Wagner, M. M. Anthony, P. Emmett, E. T. Zemanick, Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am. J. Resp. Crit. Care Med. 186, 857–865 (2012).
42. L. M. Chubiz, M. C. Lee, N. F. Delaney, C. J. Marx, FREQ-Seq: A rapid, cost-effective, sequencing-based method to determine allele frequencies directly from mixed populations. PLOS One 7, e47959 (2012).
43. E. P. Reeves, D. A. Bergin, S. Fitzgerald, E. Hayes, J. Keenan, M. Henry, P. Meleady, I. Vega-Carrascal, M. A. Murray, T. B. Low, C. McCarthy, E. O’Brien, M. Clynes, C. Gunaratnam, N. G. McElvaney, A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis. J. Cyst. Fibros. 11, 100–107 (2012).
44. A. Augarten, G. Paret, I. Avneri, H. Akons, M. Aviram, L. Bentur, H. Blau, O. Efrati, A. Szeinberg, A. Barak, E. Kerem, J. Yahav, Systemic inflammatory mediators and cystic fibrosis genotype. Clin. Exp. Med. 4, 99–102 (2004).
45. A. R. Hauser, M. Jain, M. Bar-Meir, S. A. McColley, Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin. Microbiol. Rev. 24, 29–70 (2011).
46. M. Hogardt, C. Hoboth, S. Schmoldt, C. Henke, L. Bader, J. Heesemann, Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J. Infect. Dis. 195, 70–80 (2007).
47. O. Ciofu, L. F. Mandsberg, T. Bjarnsholt, T. Wassermann, N. Høiby, Genetic adaptation of Pseudomonas aeruginosa during chronic lung infection of patients with cystic fibrosis: Strong and weak mutators with heterogeneous genetic backgrounds emerge in mucA and/or lasR mutants. Microbiology 156, 1108–1119 (2010).
48. L. Yang, L. Jelsbak, R. L. Marvig, S. Damkiær, C. T. Workman, M. H. Rau, S. K. Hansen, A. Folkesson, H. K. Johansen, O. Ciofu, N. Høiby, M. O. Sommer, S. Molin, Evolutionary dynamics of bacteria in a human host environment. Proc. Natl. Acad. Sci. U.S.A. 108, 7481–7486 (2011).
49. S. Feliziani, R. L. Marvig, A. M. Lujan, A. J. Moyano, J. A. Di Rienzo, H. Krogh Johansen, S. Molin, A. M. Smania, Coexistence and within-host evolution of diversified lineages of hypermutable Pseudomonas aeruginosa in long-term cystic fibrosis infections. PLOS Genet. 10, e1004651 (2014).
50. D. Hartl, A. Gaggar, E. Bruscia, A. Hector, V. Marcos, A. Jung, C. Greene, G. McElvaney, M. Mall, G. Döring, Innate immunity in cystic fibrosis lung disease. J. Cyst. Fibros. 11, 363–382 (2012).
51. J. F. Chmiel, M. Berger, M. W. Konstan, The role of inflammation in the pathophysiology of CF lung disease. Clin. Rev. Allergy Immunol. 23, 5–27 (2002).
52. M. Rosenfeld, R. L. Gibson, S. McNamara, J. Emerson, J. L. Burns, R. Castile, P. Hiatt, K. McCoy, C. B. Wilson, A. Inglis, A. Smith, T. R. Martin, B. W. Ramsey, Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr. Pulmonol. 32, 356–366 (2001).
53. J. Lam, R. Chan, K. Lam, J. W. Costerton, Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect. Immun. 28, 546–556 (1980).
54. A. Holm, E. Vikström, Quorum sensing communication between bacteria and human cells: Signals, targets, and functions. Front. Plant Sci. 5, 309 (2014).
55. R. S. Smith, E. R. Fedyk, T. A. Springer, N. Mukaida, B. H. Iglewski, R. P. Phipps, IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kB and activator protein-2. J. Immunol. 167, 366–374 (2001).
56. E. Vikstrom, F. Tafazoli, K. E. Magnusson, Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-L-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells. FEBS Lett. 580, 6921–6928 (2006).
57. E. K. Shiner, D. Terentyev, A. Bryan, S. Sennoune, R. Martinez-Zaguilan, G. Li, S. Gyorke, S. C. Williams, K. P. Rumbaugh, Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell. Microbiol. 8, 1601–1610 (2006).
58. Y. Glucksam-Galnoy, R. Sananes, N. Silberstein, P. Krief, V. V. Kravchenko, M. M. Meijler, T. Zor, The bacterial quorum-sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages. J. Immunol. 191, 337–344 (2013).
59. M. L. Mayer, J. A. Sheridan, C. J. Blohmke, S. E. Turvey, R. E. Hancock, The Pseudomonas aeruginosa autoinducer 3O-C12 homoserine lactone provokes hyperinflammatory responses from cystic fibrosis airway epithelial cells. PLOS One 6, e16246 (2011).
60. A. O. Azghani, J. W. Baker, S. Shetty, E. J. Miller, G. J. Bhat, Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL-8 production by alveolar epithelial cells in culture. Inflamm. Res. 51, 506–510 (2002).
61. A. O. Azghani, K. Neal, S. Idell, R. Amaro, J. W. Baker, A. Omri, U. R. Pendurthi, Mechanism of fibroblast inflammatory responses to Pseudomonas aeruginosa elastase. Microbiology 160, 547–555 (2014).
62. D. G. Storey, E. E. Ujack, I. Mitchell, H. R. Rabin, Positive correlation of algD transcription to lasB and lasA transcription by populations of Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis. Infect. Immun. 65, 4061–4067 (1997).
63. D. G. Storey, E. E. Ujack, H. R. Rabin, Population transcript accumulation of Pseudomonas aeruginosa exotoxin A and elastase in sputa from patients with cystic fibrosis. Infect. Immun. 60, 4687–4694 (1992).
64. M. C. Jaffar-Bandjee, A. Lazdunski, M. Bally, J. Carrere, J. P. Chazalette, C. Galabert, Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa. J. Clin. Microbiol. 33, 924–929 (1995).
65. D. Coin, D. Louis, J. Bernillon, M. Guinand, J. Wallach, LasA, alkaline protease and elastase in clinical strains of Pseudomonas aeruginosa: Quantification by immunochemical methods. FEMS Immunol. Med. Microbiol. 18, 175–184 (1997).
66. J. A. Schaber, N. L. Carty, N. A. McDonald, E. D. Graham, R. Cheluvappa, J. A. Griswold, A. N. Hamood, Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa. J. Med. Microbiol. 53, 841–853 (2004).
67. O. R. Pavlovskis, B. Wretlind, Assessment of protease (elastase) as a Pseudomonas aeruginosa virulence factor in experimental mouse burn infection. Infect. Immun. 24, 181–187 (1979).
68. Y. Tamura, S. Suzuki, T. Sawada, Role of elastase as a virulence factor in experimental Pseudomonas aeruginosa infection in mice. Microb. Pathog. 12, 237–244 (1992).
69. A. Schmidtchen, E. Holst, H. Tapper, L. Björck, Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth. Microb. Pathog. 34, 47–55 (2003).
70. K. G. Leidal, K. L. Munson, M. C. Johnson, G. M. Denning, Metalloproteases from Pseudomonas aeruginosa degrade human RANTES, MCP-1, and ENA-78. J. Interferon Cytokine Res. 23, 307–318 (2003).
71. R. T. Horvat, M. Clabaugh, C. Duval-Jobe, M. J. Parmely, Inactivation of human g interferon by Pseudomonas aeruginosa proteases: Elastase augments the effects of alkaline protease despite the presence of a2-macroglobulin. Infect. Immun. 57, 1668–1674 (1989).
72. R. T. Horvat, M. J. Parmely, Pseudomonas aeruginosa alkaline protease degrades human g-interferon and inhibits its bioactivity. Infect. Immun. 56, 2925–2932 (1988).
73. M. E. Hammond, G. R. Lapointe, P. H. Feucht, S. Hilt, C. A. Gallegos, C. A. Gordon, M. A. Giedlin, G. Mullenbach, P. Tekamp-Olson, IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J. Immunol. 155, 1428–1433 (1995).
74. J. Bérubé, L. Roussel, L. Nattagh, S. Rousseau, Loss of cystic fibrosis transmembrane conductance regulator function enhances activation of p38 and ERK MAPKs, increasing interleukin-6 synthesis in airway epithelial cells exposed to Pseudomonas aeruginosa. J. Biol. Chem. 285, 22299–22307 (2010).
75. M. R. Jones, L. J. Quinton, B. T. Simms, M. M. Lupa, M. S. Kogan, J. P. Mizgerd, Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia. J. Infect. Dis. 193, 360–369 (2006).
76. J. L. Johnson, E. E. Moore, D. Y. Tamura, G. Zallen, W. L. Biffl, C. C. Silliman, Interleukin-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release. J. Surg. Res. 76, 91–94 (1998).
77. A. L. Pukhalsky, N. I. Kapranov, E. A. Kalashnikova, G. V. Shmarina, L. A. Shabalova, S. N. Kokarovtseva, D. A. Pukhalskaya, N. J. Kashirskaja, O. I. Simonova, Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection. Mediators Inflamm. 8, 159–167 (1999).
78. N. Mayer-Hamblett, M. L. Aitken, F. J. Accurso, R. A. Kronmal, M. W. Konstan, J. L. Burns, S. D. Sagel, B. W. Ramsey, Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am. J. Resp. Crit. Care Med. 175, 822–828 (2007).
79. J. S. Kim, K. Okamoto, B. K. Rubin, Pulmonary function is negatively correlated with sputum inflammatory markers and cough clearability in subjects with cystic fibrosis but not those with chronic bronchitis. Chest 129, 1148–1154 (2006).
80. J. F. Alcorn, J. R. Wright, Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. J. Biol. Chem. 279, 30871–30879 (2004).
81. W. I. Mariencheck, J. F. Alcorn, S. M. Palmer, J. R. Wright, Pseudomonas aeruginosa elastase degrades surfactant proteins A and D. Am. J. Respir. Cell Mol. Biol. 28, 528–537 (2003).
82. Z. Kuang, Y. Hao, B. E. Walling, J. L. Jeffries, D. E. Ohman, G. W. Lau, Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A. PLOS One 6, e27091 (2011).
83. B. W. Bardoel, S. van der Ent, M. J. C. Pel, J. Tommassen, C. M. J. Pieterse, K. P. M. van Kessel, J. A. G. van Strijp, Pseudomonas evades immune recognition of flagellin in both mammals and plants. PLOS Pathog. 7, e1002206 (2011).
84. S. Cabrol, A. Olliver, G. B. Pier, A. Andremont, R. Ruimy, Transcription of quorum-sensing system genes in clinical and environmental isolates of Pseudomonas aeruginosa. J. Bacteriol. 185, 7222–7230 (2003).
85. L. L. Blackwood, R. M. Stone, B. H. Iglewski, J. E. Pennington, Evaluation of Pseudomonas aeruginosa exotoxin A and elastase as virulence factors in acute lung infection. Infect. Immun. 39, 198–201 (1983).
86. E. I. Lutter, S. Purighalla, J. Duong, D. G. Storey, Lethality and cooperation of Pseudomonas aeruginosa quorum-sensing mutants in Drosophila melanogaster infection models. Microbiology 158, 2125–2132 (2012).
87. J. P. Pearson, M. Feldman, B. H. Iglewski, A. Prince, Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect. Immun. 68, 4331–4334 (2000).
88. T. Köhler, G. G. Perron, A. Buckling, C. van Delden, Quorum sensing inhibition selects for virulence and cooperation in Pseudomonas aeruginosa. PLOS Pathog. 6, e1000883 (2010).
89. L. R. Hoffman, A. R. Richardson, L. S. Houston, H. D. Kulasekara, W. Martens-Habbena, M. Klausen, J. L. Burns, D. A. Stahl, D. J. Hassett, F. C. Fang, S. I. Miller, Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway. PLOS Pathog. 6, e1000712 (2010).
90. K. Heurlier, V. r. D©nervaud, M. Haenni, L. Guy, V. Krishnapillai, D. Haas, Quorum-sensing-negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis and death. J. Bacteriol. 187, 4875–4883 (2005).
91. C. N. Wilder, S. P. Diggle, M. Schuster, Cooperation and cheating in Pseudomonas aeruginosa: The roles of the las, rhl and pqs quorum-sensing systems. ISME J. 5, 1332–1343 (2011).
92. K. P. Rumbaugh, S. P. Diggle, C. M. Watters, A. Ross-Gillespie, A. S. Griffin, S. A. West, Quorum sensing and the social evolution of bacterial virulence. Curr. Biol. 19, 341–345 (2009).
93. T. H. Jakobsen, T. Bjarnsholt, P. Ø. Jensen, M. Givskov, N. Høiby, Targeting quorum sensing in Pseudomonas aeruginosa biofilms: Current and emerging inhibitors. Future Microbiol. 8, 901–921 (2013).
94. G. R. Cathcart, D. Quinn, B. Greer, P. Harriott, J. F. Lynas, B. F. Gilmore, B. Walker, Novel inhibitors of the Pseudomonas aeruginosa virulence factor LasB: A potential therapeutic approach for the attenuation of virulence mechanisms in pseudomonal infection. Antimicrob. Agents Chemother. 55, 2670–2678 (2011).
95. L. Mfuna Endam, C. Cormier, Y. Bossé, A. Filali-Mouhim, M. Desrosiers, Association of IL1A, IL1B, and TNF gene polymorphisms with chronic rhinosinusitis with and without nasal polyposis: A replication study. Arch. Otolaryngol. Head Neck Surg. 136, 187–192 (2010).
96. M. J. Bjorn, P. A. Sokol, B. H. Iglewski, Influence of iron on yields of extracellular products in Pseudomonas Aeruginosa cultures. J. Bacteriol. 138, 193–200 (1979).
97. D. E. Ohman, S. J. Cryz, B. H. Iglewski, Isolation and characterization of Pseudomonas aeruginosa PAO mutant that produces altered elastase. J. Bacteriol. 142, 836–842 (1980).
98. 4 receptor. J. Biol. Chem. 268, 9280–9286 (1993).
99. L. Roussel, S. Rousseau, IL-17 primes airway epithelial cells lacking functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) to increase NOD1 responses. Biochem. Biophys. Res. Commun. 391, 505–509 (2010).
100. G. Wojewodka, J. B. De Sanctis, J. Bernier, J. Berube, H. G. Ahlgren, J. Gruber, J. Landry, L. C. Lands, D. Nguyen, S. Rousseau, A. Benedetti, E. Matouk, D. Radzioch, Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients. PLOS One 9, e88567 (2014).
101. H. Li, R. Durbin, Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010).
102. T. T. Hoang, R. R. Karkhoff-Schweizer, A. J. Kutchma, H. P. Schweizer, A broad-host-range Flp-FRT recombination system for site-specific excision of chromosomally-located DNA sequences: Application for isolation of unmarked Pseudomonas aeruginosa mutants. Gene 212, 77–86 (1998).
103. M. Khakimova, H. Ahlgren, J. J. Harrison, A. English, D. Nguyen, The stringent response controls catalases in Pseudomonas aeruginosa: Implications for hydrogen peroxide and antibiotic tolerance. J. Bacteriol. 195, 2011–2020 (2013).
104. A. B. Semmler, C. B. Whitchurch, J. S. Mattick, A re-examination of twitching motility in Pseudomonas aeruginosa. Microbiology 145, 2863–2873 (1999).
105. D. W. Essar, L. Eberly, A. Hadero, I. P. Crawford, Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: Interchangeability of the two anthranilate synthases and evolutionary implications. J. Bacteriol. 172, 884–900 (1990).
106. J. M. Meyer, A. Neely, A. Stintzi, C. Georges, I. A. Holder, Pyoverdin is essential for virulence of Pseudomonas aeruginosa. Infect. Immun. 64, 518–523 (1996).
107. J. A. Hobden, Pseudomonas aeruginosa proteases and corneal virulence. DNA Cell Biol. 21, 391–396 (2002).
108. M. C. Wolfgang, V. T. Lee, M. E. Gilmore, S. Lory, Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway. Dev. Cell 4, 253–263 (2003).
109. S. A. Beatson, C. B. Whitchurch, A. B. Semmler, J. S. Mattick, Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J. Bacteriol. 184, 3598–3604 (2002).