Pseudomonas pp 141-175 | Cite as

Emergence of Pseudomonas aeruginosa in Cystic Fibrosis Lung Infections

  • Joanna B. Goldberg


Pseudomonas aeruginosa is typically considered an opportunistic bacterial pathogen, only affecting individuals with a compromised immune system. Despite the presence of a seemingly intact immune system, patients with the disease cystic fibrosis (CF) are uniquely susceptible to lung infections with P. aeruginosa. Chronic lung infections with this bacterium are the major cause of morbidity and mortality in this patient population. This chapter reviews the literature on the emergence of P. aeruginosa in chronic lung infections in CF, an understanding of which may identify strategies for future drug development.


Cystic Fibrosis Respiratory Syncytial Virus Cystic Fibrosis Patient Cystic Fibrosis Lung Airway Surface Liquid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Strausbaugh, S.D. and Davis., P.B. (2007) Cystic fibrosis: a review of epidemiology and pathobiology. Clin. Chest. Med. 28: 279–288.PubMedGoogle Scholar
  2. 2.
    Riordan, J.R., Rommens, J.M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.L., et al. (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245: 1066–1073.PubMedGoogle Scholar
  3. 3.
    Welsh, M.J. and Smith., A.E. (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73: 1251–1254.PubMedGoogle Scholar
  4. 4.
    Collaco, J.M. and Cutting., G.R. (2008) Update on gene modifiers in cystic fibrosis. Curr. Opin. Pulm. Med. 14: 559–566.PubMedGoogle Scholar
  5. 5.
    Gu, Y., Harley, I.T., Henderson, L.B., Aronow, B.J., Vietor, I., Huber, L.A., Harley, J.B., Kilpatrick, J.R., Langefeld, C.D., Williams, A.H., Jegga, A.G., Chen, J., Wills-Karp, M., Arshad, S.H., Ewart, S.L., Thio, C.L., Flick, L.M., Filippi, M.D., Grimes, H.L., Drumm, M.L., Cutting, G.R., Knowles, M.R. and Karp., C.L. (2009) Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature 458:1039–1042.Google Scholar
  6. 6.
    Doring, G. and Gulbins., E. (2009) Cystic fibrosis and innate immunity: how chloride channel mutations provoke lung disease. Cell Microbiol. 11: 208–216.PubMedGoogle Scholar
  7. 7.
    Teichgraber, V., Ulrich, M., Endlich, N., Riethmuller, J., Wilker, B., De Oliveira-Munding, C.C., van Heeckeren, A.M., Barr, M.L., von Kurthy, G., Schmid, K.W., Weller, M., Tummler, B., Lang, F., Grassme, H., Doring, G. and Gulbins., E. (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14: 382–391.PubMedGoogle Scholar
  8. 8.
    Campodonico, V.L., Gadjeva, M., Paradis-Bleau, C., Uluer, A. and Pier., G.B. (2008) Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis. Trends Mol. Med. 14: 120–133.PubMedGoogle Scholar
  9. 9.
    Pier, G.B. (2000) Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. Proc. Natl. Acad. Sci. U.S.A 97: 8822–8828.PubMedGoogle Scholar
  10. 10.
    Esen, M., Grassme, H., Riethmuller, J., Riehle, A., Fassbender, K. and Gulbins., E. (2001) Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn. Infect. Immun. 69: 281–287.PubMedGoogle Scholar
  11. 11.
    Darling, K.E., Dewar, A. and Evans., T.J. (2004) Role of the cystic fibrosis transmembrane conductance regulator in internalization of Pseudomonas aeruginosa by polarized respiratory epithelial cells. Cell Microbiol. 6: 521–533.PubMedGoogle Scholar
  12. 12.
    Baltimore, R.S., Christie, C.D. and Smith., G.J. (1989) Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration. Am. Rev. Respir. Dis. 140: 1650–1661.PubMedGoogle Scholar
  13. 13.
    Godfrey, R.W., Severs, N.J. and Jeffery., P.K. (1993) Structural alterations of airway epithelial tight junctions in cystic fibrosis: comparison of transplant and postmortem tissue. Am. J. Respir. Cell Mol. Biol. 9: 148–156.PubMedGoogle Scholar
  14. 14.
    Jeffery, P.K. and Brain., A.P. (1988) Surface morphology of human airway mucosa: normal, carcinoma or cystic fibrosis. Scanning Microsc. 2: 553–560.PubMedGoogle Scholar
  15. 15.
    Worlitzsch, D., Tarran, R., Ulrich, M., Schwab, U., Cekici, A., Meyer, K.C., Birrer, P., Bellon, G., Berger, J., Weiss, T., Botzenhart, K., Yankaskas, J.R., Randell, S., Boucher, R.C. and Doring., G. (2002) Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Investig. 109: 317–325.PubMedGoogle Scholar
  16. 16.
    Pier, G.B., Grout, M., Zaidi, T.S., Olsen, J.C., Johnson, L.G., Yankaskas, J.R. and Goldberg., J.B. (1996) Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 271: 64–67.PubMedGoogle Scholar
  17. 17.
    Gomez, M.I. and Prince., A. (2007) Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr. Opin. Pharmacol. 7: 244–251.PubMedGoogle Scholar
  18. 18.
    Jacquot, J., Tabary, O., Le Rouzic, P. and Clement., A. (2008) Airway epithelial cell inflammatory signalling in cystic fibrosis. Int. J. Biochem. Cell Biol. 40: 1703–1715.PubMedGoogle Scholar
  19. 19.
    Henry, R.L., Mellis, C.M. and Petrovic., L. (1992) Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis. Pediatr. Pulmonol. 12: 158–161.PubMedGoogle Scholar
  20. 20.
    Li, Z., Kosorok, M.R., Farrell, P.M., Laxova, A., West, S.E., Green, C.G., Collins, J., Rock, M.J. and Splaingard., M.L. (2005) Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis. J. Am. Med. Assoc. 293: 581–588.Google Scholar
  21. 21.
    Nixon, G.M., Armstrong, D.S., Carzino, R., Carlin, J.B., Olinsky, A., Robertson, C.F. and Grimwood., K. (2001) Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J. Pediatr. 138: 699–704.PubMedGoogle Scholar
  22. 22.
    Harrison, F. (2007) Microbial ecology of the cystic fibrosis lung. Microbiology 153: 917–923.PubMedGoogle Scholar
  23. 23.
    Sibley, C.D., Rabin, H. and Surette., M.G. (2006) Cystic fibrosis: a polymicrobial infectious disease. Future Microbiol. 1: 53–61.PubMedGoogle Scholar
  24. 24.
    van Ewijk, B.E., van der Zalm, M.M., Wolfs, T.F., Fleer, A., Kimpen, J.L., Wilbrink, B. and van der Ent., C.K. (2008) Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study. Pediatrics 122: 1171–1176.PubMedGoogle Scholar
  25. 25.
    van Ewijk, B.E., van der Zalm, M.M., Wolfs, T.F. and van der Ent., C.K. (2005) Viral respiratory infections in cystic fibrosis. J. Cystic Fibrosis 4(Suppl 2): 31–36.Google Scholar
  26. 26.
    Abman, S.H., Ogle, J.W., Butler-Simon, N., Rumack, C.M. and Accurso., F.J. (1988) Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J. Pediatr. 113: 826–830.PubMedGoogle Scholar
  27. 27.
    Johansen, H.K. and Hoiby., N. (1992) Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark. Thorax 47: 109–111.PubMedGoogle Scholar
  28. 28.
    Collinson, J., Nicholson, K.G., Cancio, E., Ashman, J., Ireland, D.C., Hammersley, V., Kent, J. and O‘Callaghan., C. (1996) Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 51: 1115–1122.PubMedGoogle Scholar
  29. 29.
    Ramphal, R., Small, P.M., Shands, J.W., Jr., Fischlschweiger, W. and Small, P.A., Jr. (1980) Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation. Infect. Immun. 27: 614–619.PubMedGoogle Scholar
  30. 30.
    Van Ewijk, B.E., Wolfs, T.F., Aerts, P.C., Van Kessel, K.P., Fleer, A., Kimpen, J.L. and Van der Ent., C.K. (2007) RSV mediates Pseudomonas aeruginosa binding to cystic fibrosis and normal epithelial cells. Pediatr. Res. 61: 398–403.PubMedGoogle Scholar
  31. 31.
    Smyth, A. (2005) Prophylactic antibiotics in cystic fibrosis: a conviction without evidence? Pediatr. Pulmonol. 40: 471–476.PubMedGoogle Scholar
  32. 32.
    Stutman, H.R., Lieberman, J.M., Nussbaum, E. and Marks., M.I. (2002) Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial. J. Pediatr. 140: 299–305.PubMedGoogle Scholar
  33. 33.
    Levy, H., Kalish, L.A., Cannon, C.L., Garcia, K.C., Gerard, C., Goldmann, D., Pier, G.B., Weiss, S.T. and Colin., A.A. (2008) Predictors of mucoid Pseudomonas colonization in cystic fibrosis patients. Pediatr. Pulmonol. 43: 463–471.PubMedGoogle Scholar
  34. 34.
    Sagel, S.D., Gibson, R.L., Emerson, J., McNamara, S., Burns, J.L., Wagener, J.S. and Ramsey., B.W. (2009) Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. J. Pediatr. 154:183–188.PubMedGoogle Scholar
  35. 35.
    Mashburn, L.M., Jett, A.M., Akins, D.R. and Whiteley., M. (2005) Staphylococcus aureus serves as an iron source for Pseudomonas aeruginosa during in vivo coculture. J. Bacteriol. 187: 554–566.PubMedGoogle Scholar
  36. 36.
    Lamont, I.L., Konings, A.F. and Reid., D.W. (2009) Iron acquisition by Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis. Biometals 22: 53–60.PubMedGoogle Scholar
  37. 37.
    Hoffman, L.R., Deziel, E., D‘Argenio, D.A., Lepine, F., Emerson, J., McNamara, S., Gibson, R.L., Ramsey, B.W. and Miller., S.I. (2006) Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 103: 19890–19895.PubMedGoogle Scholar
  38. 38.
    Starner, T.D., Zhang, N., Kim, G., Apicella, M.A. and McCray, P.B., Jr. (2006) Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am. J. Respir. Crit. Care Med. 174: 213–220.PubMedGoogle Scholar
  39. 39.
    Garcia-Vidal, C., Almagro, P., Romani, V., Rodriguez-Carballeira, M., Cuchi, E., Canales, L., Blasco, D., Heredia, J.L. and Garau., J. (2009) Pseudomonas aeruginosa in patients hospitalized for COPD exacerbation. A prospective study. Eur. Respir. J. 34:1072–1078.Google Scholar
  40. 40.
    Martinez-Garcia, M.A., Soler-Cataluna, J.J., Perpina-Tordera, M., Roman-Sanchez, P. and Soriano., J. (2007) Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis. Chest 132: 1565–1572.PubMedGoogle Scholar
  41. 41.
    Martinez-Solano, L., Macia, M.D., Fajardo, A., Oliver, A. and Martinez., J.L. (2008) Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clin. Infect. Dis. 47: 1526–1533.PubMedGoogle Scholar
  42. 42.
    Rosenfeld, M., Ramsey, B.W. and Gibson., R.L. (2003) Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Curr. Opin. Pulm. Med. 9: 492–497.PubMedGoogle Scholar
  43. 43.
    Rosenfeld, M., Gibson, R.L., McNamara, S., Emerson, J., Burns, J.L., Castile, R., Hiatt, P., McCoy, K., Wilson, C.B., Inglis, A., Smith, A., Martin, T.R. and Ramsey., B.W. (2001) Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr. Pulmonol. 32: 356–366.PubMedGoogle Scholar
  44. 44.
    Knudsen, P.K., Olesen, H.V., Hoiby, N., Johannesson, M., Karpati, F., Laerum, B.N., Meyer, P., Pressler, T. and Lindblad., A. (2009) Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis centres in Denmark, Norway and Sweden. J. Cystic Fibrosis 8: 135–142.Google Scholar
  45. 45.
    Aaron, S.D. (2006) Pseudomonas aeruginosa and cystic fibrosis–a nasty bug gets nastier. Respiration; Int. Rev. Thor. Dis. 73: 16–17.Google Scholar
  46. 46.
    Emerson, J., Rosenfeld, M., McNamara, S., Ramsey, B. and Gibson., R.L. (2002) Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr. Pulmonol. 34: 91–100.PubMedGoogle Scholar
  47. 47.
    Mahenthiralingam, E., Urban, T.A. and Goldberg., J.B. (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nat. Rev. Microbiol. 3: 144–156.PubMedGoogle Scholar
  48. 48.
    Olivier, K.N. (2004) The natural history of nontuberculous mycobacteria in patients with cystic fibrosis. Paediatr. Respir. Rev. 5(Suppl A): S213-S216.PubMedGoogle Scholar
  49. 49.
    Foweraker, J. (2009) Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br. Med, Bull, 89: 93–110.Google Scholar
  50. 50.
    Davies, J.C. and Bilton., D. (2009) Bugs, biofilms, and resistance in cystic fibrosis. Respir. Care 54: 628–640.PubMedGoogle Scholar
  51. 51.
    Pihet, M., Carrere, J., Cimon, B., Chabasse, D., Delhaes, L., Symoens, F. and Bouchara., J.P. (2009) Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis–a review. Med. Mycology 47: 387–397.Google Scholar
  52. 52.
    Harris, J.K., De Groote, M.A., Sagel, S.D., Zemanick, E.T., Kapsner, R., Penvari, C., Kaess, H., Deterding, R.R., Accurso, F.J. and Pace., N.R. (2007) Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. Proc. Natl. Acad. Sci. USA 104: 20529–20533.PubMedGoogle Scholar
  53. 53.
    Bittar, F., Richet, H., Dubus, J.C., Reynaud-Gaubert, M., Stremler, N., Sarles, J., Raoult, D. and Rolain., J.M. (2008) Molecular detection of multiple emerging pathogens in sputa from cystic fibrosis patients. PLoS ONE 3: e2908.PubMedGoogle Scholar
  54. 54.
    Sibley, C.D., Parkins, M.D., Rabin, H.R., Duan, K., Norgaard, J.C. and Surette., M.G. (2008) A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 105: 15070–15075.PubMedGoogle Scholar
  55. 55.
    Kukavica-Ibrulj, I. and Levesque., R.C. (2008) Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies. Lab. Anim. 42: 389–412.PubMedGoogle Scholar
  56. 56.
    Cash, H.A., Woods, D.E., McCullough, B., Johanson, W.G., Jr. and Bass., J.A. (1979) A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am. Rev. Respir. Dis. 119: 453–459.PubMedGoogle Scholar
  57. 57.
    Guilbault, C., Saeed, Z., Downey, G.P. and Radzioch., D. (2007) Cystic fibrosis mouse models. Am. J. Respir. Cell Mol. Biol. 36: 1–7.PubMedGoogle Scholar
  58. 58.
    Stotland, P.K., Radzioch, D. and Stevenson., M.M. (2000) Mouse models of chronic lung infection with Pseudomonas aeruginosa: models for the study of cystic fibrosis. Pediatr. Pulmonol. 30: 413–424.PubMedGoogle Scholar
  59. 59.
    Coleman, F.T., Mueschenborn, S., Meluleni, G., Ray, C., Carey, V.J., Vargas, S.O., Cannon, C.L., Ausubel, F.M. and Pier., G.B. (2003) Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc. Natl. Acad. Sci. USA 100: 1949–1954.PubMedGoogle Scholar
  60. 60.
    Mahajan-Miklos, S., Rahme, L.G. and Ausubel., F.M. (2000) Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol. Microbiol. 37: 981–988.PubMedGoogle Scholar
  61. 61.
    Rogers, C.S., Stoltz, D.A., Meyerholz, D.K., Ostedgaard, L.S., Rokhlina, T., Taft, P.J., Rogan, M.P., Pezzulo, A.A., Karp, P.H., Itani, O.A., Kabel, A.C., Wohlford-Lenane, C.L., Davis, G.J., Hanfland, R.A., Smith, T.L., Samuel, M., Wax, D., Murphy, C.N., Rieke, A., Whitworth, K., Uc, A., Starner, T.D., Brogden, K.A., Shilyansky, J., McCray, P.B., Jr., Zabner, J., Prather, R.S. and Welsh., M.J. (2008) Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321: 1837–1841.PubMedGoogle Scholar
  62. 62.
    Khan, T.Z., Wagener, J.S., Bost, T., Martinez, J., Accurso, F.J. and Riches., D.W. (1995) Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 151: 1075–1082.PubMedGoogle Scholar
  63. 63.
    Tummler, B., Bosshammer, J., Breitenstein, S., Brockhausen, I., Gudowius, P., Herrmann, C., Herrmann, S., Heuer, T., Kubesch, P., Mekus, F., Romling, U., Schmidt, K.D., Spangenberg, C. and Walter., S. (1997) Infections with Pseudomonas aeruginosa in patients with cystic fibrosis. Behring Institute Mitteilungen 98: 249–255.PubMedGoogle Scholar
  64. 64.
    Ohman, D.E. and Chakrabarty., A.M. (1982) Utilization of human respiratory secretions by mucoid Pseudomonas aeruginosa of cystic fibrosis origin. Infect. Immun. 37: 662–669.PubMedGoogle Scholar
  65. 65.
    Luzar, M.A., Thomassen, M.J. and Montie., T.C. (1985) Flagella and motility alterations in Pseudomonas aeruginosa strains from patients with cystic fibrosis: relationship to patient clinical condition. Infect. Immun. 50: 577–582.PubMedGoogle Scholar
  66. 66.
    Mahenthiralingam, E., Campbell, M.E. and Speert., D.P. (1994) Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect. Immun. 62: 596–605.PubMedGoogle Scholar
  67. 67.
    Hancock, R.E., Mutharia, L.M., Chan, L., Darveau, R.P., Speert, D.P. and Pier., G.B. (1983) Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect. Immun. 42: 170–177.PubMedGoogle Scholar
  68. 68.
    Evans, L.R. and Linker., A. (1973) Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa. J. Bacteriol. 116: 915–924.PubMedGoogle Scholar
  69. 69.
    Linker, A. and Jones., R.S. (1966) A new polysaccharide resembling alginic acid isolated from Pseudomonads. J. Biol. Chem. 241: 3845–3851.PubMedGoogle Scholar
  70. 70.
    Speert, D.P., Farmer, S.W., Campbell, M.E., Musser, J.M., Selander, R.K. and Kuo., S. (1990) Conversion of Pseudomonas aeruginosa to the phenotype characteristic of strains from patients with cystic fibrosis. J. Clin. Microbiol. 28: 188–194.PubMedGoogle Scholar
  71. 71.
    Davies, D. (2003) Understanding biofilm resistance to antibacterial agents. Nat. Rev. 2: 114–122.Google Scholar
  72. 72.
    Ramsey, D.M. and Wozniak., D.J. (2005) Understanding the control of Pseudomonas aeruginosa alginate synthesis and the prospects for management of chronic infections in cystic fibrosis. Mol. Microbiol. 56: 309–322.PubMedGoogle Scholar
  73. 73.
    Bragonzi, A., Paroni, M., Nonis, A.,Cramer, N., Montanari, S., Rejman, J., Di Serio, C., Doring, G. and Tuemmler., B. (2009) Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am. J. Respir. Crit. Care Med. 180:138–145.Google Scholar
  74. 74.
    Boucher, J.C., Yu, H., Mudd, M.H. and Deretic., V. (1997) Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect. Immun. 65: 3838–3846.PubMedGoogle Scholar
  75. 75.
    Bragonzi, A., Wiehlmann, L., Klockgether, J., Cramer, N., Worlitzsch, D., Doring, G. and Tummler., B. (2006) Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 152: 3261–3269.PubMedGoogle Scholar
  76. 76.
    Mathee, K., Ciofu, O., Sternberg, C., Lindum, P.W., Campbell, J.I., Jensen, P., Johnsen, A.H., Givskov, M., Ohman, D.E., Molin, S., Hoiby, N. and Kharazmi., A. (1999) Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung. Microbiology 145: 1349–1357.PubMedGoogle Scholar
  77. 77.
    DeVries, C.A. and Ohman., D.E. (1994) Mucoid-to-nonmucoid conversion in alginate-producing Pseudomonas aeruginosa often results from spontaneous mutations in algT, encoding a putative alternate sigma factor, and shows evidence for autoregulation. J. Bacteriol. 176: 6677–6687.PubMedGoogle Scholar
  78. 78.
    Firoved, A.M. and Deretic., V. (2003) Microarray analysis of global gene expression in mucoid Pseudomonas aeruginosa. J. Bacteriol. 185: 1071–1081.PubMedGoogle Scholar
  79. 79.
    Wu, W., Badrane, H., Arora, S., Baker, H.V. and Jin., S. (2004) MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa. J. Bacteriol. 186: 7575–7585.PubMedGoogle Scholar
  80. 80.
    Rao, J., DiGiandomenico, A., Unger, J., Bao, Y., Polanowska-Grabowska, R.K. and Goldberg., J.B. (2008) A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa. Microbiology 154: 654–665.PubMedGoogle Scholar
  81. 81.
    Hanna, S.L., Sherman, N.E., Kinter, M.T. and Goldberg, J.B. (2000) Comparison of proteins expressed by Pseudomonas aeruginosa strains representing initial and chronic isolates from a cystic fibrosis patient: an analysis by 2-D gel electrophoresis and capillary column liquid chromatography-tandem mass spectrometry. Microbiology 146: 2495–2508.PubMedGoogle Scholar
  82. 82.
    Lam, J., Chan, R., Lam, K. and Costerton., J.W. (1980) Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect. Immun. 28: 546–556.PubMedGoogle Scholar
  83. 83.
    Wozniak, D.J., Wyckoff, T.J., Starkey, M., Keyser, R., Azadi, P., O‘Toole, G.A. and Parsek., M.R. (2003) Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms. Proc. Natl. Acad. Sci. USA 100: 7907–7912.PubMedGoogle Scholar
  84. 84.
    Lee, B., Haagensen, J.A., Ciofu, O., Andersen, J.B., Hoiby, N. and Molin., S. (2005) Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. J. Clin. Microbiol. 43: 5247–5255.PubMedGoogle Scholar
  85. 85.
    Ryder, C., Byrd, M. and Wozniak., D.J. (2007) Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr. Opin. Microbiol. 10: 644–648.PubMedGoogle Scholar
  86. 86.
    Hentzer, M., Teitzel, G.M., Balzer, G.J., Heydorn, A., Molin, S., Givskov, M. and Parsek., M.R. (2001) Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J. Bacteriol. 183: 5395–5401.PubMedGoogle Scholar
  87. 87.
    Bjarnsholt, T., Jensen, P.O., Fiandaca, M.J., Pedersen, J., Hansen, C.R., Andersen, C.B., Pressler, T., Givskov, M. and Hoiby., N. (2009) Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol 44: 547–558.PubMedGoogle Scholar
  88. 88.
    Hassett, D.J., Sutton, M.D., Schurr, M.J., Herr, A.B., Caldwell, C.C. and Matu., J.O. (2009) Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways. Trends Microbiol. 17: 130–138.PubMedGoogle Scholar
  89. 89.
    Wagner, V.E. and Iglewski., B.H. (2008) P. aeruginosa biofilms in CF Infection. Clin. Rev. Allergy Immunol 35: 124–134.PubMedGoogle Scholar
  90. 90.
    Singh, P.K., Schaefer, A.L., Parsek, M.R., Moninger, T.O., Welsh, M.J. and Greenberg., E.P. (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407: 762–764.PubMedGoogle Scholar
  91. 91.
    Yahr, T.L. and Wolfgang., M.C. (2006) Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system. Mol. Microbiol 62: 631–640.PubMedGoogle Scholar
  92. 92.
    Feltman, H., Schulert, G., Khan, S., Jain, M., Peterson, L. and Hauser., A.R. (2001) Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa. Microbiology 147: 2659–2669.PubMedGoogle Scholar
  93. 93.
    Jain, M., Ramirez, D., Seshadri, R., Cullina, J.F., Powers, C.A., Schulert, G.S., Bar-Meir, M., Sullivan, C.L., McColley, S.A. and Hauser., A.R. (2004) Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis. J. Clin. Microbiol. 42: 5229–5237.PubMedGoogle Scholar
  94. 94.
    Jain, M., Bar-Meir, M., McColley, S., Cullina, J., Potter, E., Powers, C., Prickett, M., Seshadri, R., Jovanovic, B., Petrocheilou, A., King, J.D. and Hauser., A.R. (2008) Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection. Transl. Res. 152: 257–264.PubMedGoogle Scholar
  95. 95.
    Dacheux, D., Attree, I. and Toussaint., B. (2001) Expression of ExsA in trans confers type III secretion system-dependent cytotoxicity on noncytotoxic Pseudomonas aeruginosa cystic fibrosis isolates. Infect. Immun. 69: 538–542.PubMedGoogle Scholar
  96. 96.
    Goodman, A.L., Kulasekara, B., Rietsch, A., Boyd, D., Smith, R.S. and Lory., S. (2004) A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev. Cell 7: 745–754.PubMedGoogle Scholar
  97. 97.
    Garrett, E.S., Perlegas, D. and Wozniak., D.J. (1999) Negative control of flagellum synthesis in Pseudomonas aeruginosa is modulated by the alternative sigma factor AlgT (AlgU). J. Bacteriol. 181: 7401–7404.PubMedGoogle Scholar
  98. 98.
    Tart, A.H., Blanks, M.J. and Wozniak., D.J. (2006) The AlgT-dependent transcriptional regulator AmrZ (AlgZ) inhibits flagellum biosynthesis in mucoid, nonmotile Pseudomonas aeruginosa cystic fibrosis isolates. J. Bacteriol. 188: 6483–6489.PubMedGoogle Scholar
  99. 99.
    Tart, A.H., Wolfgang, M.C. and Wozniak., D.J. (2005) The alternative sigma factor AlgT represses Pseudomonas aeruginosa flagellum biosynthesis by inhibiting expression of fleQ. J. Bacteriol. 187: 7955–7962.PubMedGoogle Scholar
  100. 100.
    Wolfgang, M.C., Jyot, J., Goodman, A.L., Ramphal, R. and Lory., S. (2004) Pseudomonas aeruginosa regulates flagellin expression as part of a global response to airway fluid from cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 101: 6664–6668.PubMedGoogle Scholar
  101. 101.
    Sonawane, A., Jyot, J., During, R. and Ramphal., R. (2006) Neutrophil elastase, an innate immunity effector molecule, represses flagellin transcription in Pseudomonas aeruginosa. Infect. Immun. 74: 6682–6689.PubMedGoogle Scholar
  102. 102.
    Luzar, M.A. and Montie., T.C. (1985) Avirulence and altered physiological properties of cystic fibrosis strains of Pseudomonas aeruginosa. Infect. Immun. 50: 572–576.PubMedGoogle Scholar
  103. 103.
    Evans, D.J., Pier, G.B., Coyne, M.J., Jr. and Goldberg., J.B. (1994) The rfb locus from Pseudomonas aeruginosa strain PA103 promotes the expression of O antigen by both LPS-rough and LPS-smooth isolates from cystic fibrosis patients. Mol. Microbiol. 13: 427–434.PubMedGoogle Scholar
  104. 104.
    Ernst, R.K., Yi, E.C., Guo, L., Lim, K.B., Burns, J.L., Hackett, M. and Miller., S.I. (1999) Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286: 1561–1565.PubMedGoogle Scholar
  105. 105.
    Hajjar, A.M., Ernst, R.K., Tsai, J.H., Wilson, C.B. and Miller., S.I. (2002) Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat. Immunol. 3: 354–359.PubMedGoogle Scholar
  106. 106.
    Ernst, R.K., Moskowitz, S.M., Emerson, J.C., Kraig, G.M., Adams, K.N., Harvey, M.D., Ramsey, B., Speert, D.P., Burns, J.L. and Miller., S.I. (2007) Unique lipid A modifications in Pseudomonas aeruginosa isolated from the airways of patients with cystic fibrosis. J. Infect. Dis. 196: 1088–1092.PubMedGoogle Scholar
  107. 107.
    Ernst, R.K., Adams, K.N., Moskowitz, S.M., Kraig, G.M., Kawasaki, K., Stead, C.M., Trent, M.S. and Miller., S.I. (2006) The Pseudomonas aeruginosa lipid A deacylase: selection for expression and loss within the cystic fibrosis airway. J. Bacteriol. 188: 191–201.PubMedGoogle Scholar
  108. 108.
    Mosser, J.L. and Tomasz., A. (1970) Choline-containing teichoic acid as a structural component of pneumococcal cell wall and its role in sensitivity to lysis by an autolytic enzyme. J. Biol. Chem. 245: 287–298.PubMedGoogle Scholar
  109. 109.
    Weiser, J.N., Shchepetov, M. and Chong., S.T. (1997) Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzae. Infect. Immun. 65: 943–950.PubMedGoogle Scholar
  110. 110.
    Weiser, J.N., Goldberg, J.B., Pan, N., Wilson, L. and Virji., M. (1998) The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeae. Infect. Immun. 66: 4263–4267.PubMedGoogle Scholar
  111. 111.
    Barbier, M., Oliver, A., Rao, J., Hanna, S.L., Goldberg, J.B. and Alberti., S. (2008) Novel phosphorylcholine-containing protein of Pseudomonas aeruginosa chronic infection isolates interacts with airway epithelial cells. J. Infect. Dis. 197: 465–473.PubMedGoogle Scholar
  112. 112.
    Taylor, R.F., Hodson, M.E. and Pitt., T.L. (1992) Auxotrophy of Pseudomonas aeruginosa in cystic fibrosis. FEMS Microbiol. Lett. 71: 243–246.PubMedGoogle Scholar
  113. 113.
    Barth, A.L. and Pitt., T.L. (1995) Auxotrophic variants of Pseudomonas aeruginosa are selected from prototrophic wild-type strains in respiratory infections in patients with cystic fibrosis. J. Clin. Microbiol. 33: 37–40.PubMedGoogle Scholar
  114. 114.
    Barth, A.L. and Pitt., T.L. (1996) The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa. J. Med. Microbiol. 45: 110–119.PubMedGoogle Scholar
  115. 115.
    Palmer, K.L., Aye, L.M. and Whiteley., M. (2007) Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J. Bacteriol. 189: 8079–8087.PubMedGoogle Scholar
  116. 116.
    Platt, M.D., Schurr, M.J., Sauer, K., Vazquez, G., Kukavica-Ibrulj, I., Potvin, E., Levesque, R.C., Fedynak, A., Brinkman, F.S., Schurr, J., Hwang, S.H., Lau, G.W., Limbach, P.A., Rowe, J.J., Lieberman, M.A., Barraud, N., Webb, J., Kjelleberg, S., Hunt, D.F. and Hassett., D.J. (2008) Proteomic, microarray, and signature-tagged mutagenesis analyses of anaerobic Pseudomonas aeruginosa at pH 6.5, likely representing chronic, late-stage cystic fibrosis airway conditions. J. Bacteriol. 190: 2739–2758.PubMedGoogle Scholar
  117. 117.
    Silo-Suh, L., Suh, S.J., Phibbs, P.V. and Ohman., D.E. (2005) Adaptations of Pseudomonas aeruginosa to the cystic fibrosis lung environment can include deregulation of zwf, encoding glucose-6-phosphate dehydrogenase. J. Bacteriol. 187: 7561–7568.PubMedGoogle Scholar
  118. 118.
    Hancock, R.E. (1998) Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin. Infect. Dis. 27(Suppl 1): S93–S99.PubMedGoogle Scholar
  119. 119.
    Stover, C.K., Pham, X.Q., Erwin, A.L., Mizoguchi, S.D., Warrener, P., Hickey, M.J., Brinkman, F.S., Hufnagle, W.O., Kowalik, D.J., Lagrou, M., Garber, R.L., Goltry, L., Tolentino, E., Westbrock-Wadman, S., Yuan, Y., Brody, L.L., Coulter, S.N., Folger, K.R., Kas, A., Larbig, K., Lim, R., Smith, K., Spencer, D., Wong, G.K., Wu, Z., Paulsen, I.T., Reizer, J., Saier, M.H., Hancock, R.E., Lory, S. and Olson., M.V. (2000) Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406: 959–964.PubMedGoogle Scholar
  120. 120.
    Wolfgang, M.C., Kulasekara, B.R., Liang, X., Boyd, D., Wu, K., Yang, Q., Miyada, C.G. and Lory., S. (2003) Conservation of genome content and virulence determinants among clinical and environmental isolates of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 100: 8484–8489.PubMedGoogle Scholar
  121. 121.
    Ernst, R.K., D‘Argenio, D.A., Ichikawa, J.K., Bangera, M.G., Selgrade, S., Burns, J.L., Hiatt, P., McCoy, K., Brittnacher, M., Kas, A., Spencer, D.H., Olson, M.V., Ramsey, B.W., Lory, S. and Miller., S.I. (2003) Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis. Environ. Microbiol. 5: 1341–1349.PubMedGoogle Scholar
  122. 122.
    Spencer, D.H., Kas, A., Smith, E.E., Raymond, C.K., Sims, E.H., Hastings, M., Burns, J.L., Kaul, R. and Olson., M.V. (2003) Whole-genome sequence variation among multiple isolates of Pseudomonas aeruginosa. J. Bacteriol. 185: 1316–1325.PubMedGoogle Scholar
  123. 123.
    Smith, E.E., Buckley, D.G., Wu, Z., Saenphimmachak, C., Hoffman, L.R., D‘Argenio, D.A., Miller, S.I., Ramsey, B.W., Speert, D.P., Moskowitz, S.M., Burns, J.L., Kaul, R. and Olson., M.V. (2006) Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. U.S.A 103: 8487–8492.PubMedGoogle Scholar
  124. 124.
    Hoffman, L.R., Kulasekara, H.D., Emerson, J., Houston, L.S., Burns, J.L., Ramsey, B.W. and Miller., S.I. (2009) Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J. Cystic Fibrosis 8: 66–70.Google Scholar
  125. 125.
    Mathee, K., Narasimhan, G., Valdes, C., Qiu, X., Matewish, J.M., Koehrsen, M., Rokas, A., Yandava, C.N., Engels, R., Zeng, E., Olavarietta, R., Doud, M., Smith, R.S., Montgomery, P., White, J.R., Godfrey, P.A., Kodira, C., Birren, B., Galagan, J.E. and Lory., S. (2008) Dynamics of Pseudomonas aeruginosa genome evolution. Proc. Natl. Acad. Sci. U.S.A 105: 3100–3105.PubMedGoogle Scholar
  126. 126.
    Jones, A.M., Govan, J.R., Doherty, C.J., Dodd, M.E., Isalska, B.J., Stanbridge, T.N. and Webb., A.K. (2001) Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic. Lancet 358: 557–558.PubMedGoogle Scholar
  127. 127.
    Winstanley, C., Langille, M.G., Fothergill, J.L., Kukavica-Ibrulj, I., Paradis-Bleau, C., Sanschagrin, F., Thomson, N.R., Winsor, G.L., Quail, M.A., Lennard, N., Bignell, A., Clarke, L., Seeger, K., Saunders, D., Harris, D., Parkhill, J., Hancock, R.E., Brinkman, F.S. and Levesque., R.C. (2009) Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res. 19: 12–23.PubMedGoogle Scholar
  128. 128.
    Fothergill, J.L., Panagea, S., Hart, C.A., Walshaw, M.J., Pitt, T.L. and Winstanley., C. (2007) Widespread pyocyanin over-production among isolates of a cystic fibrosis epidemic strain. BMC Microbiol. 7: 45.PubMedGoogle Scholar
  129. 129.
    Oliver, A., Canton, R., Campo, P., Baquero, F. and Blazquez., J. (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288: 1251–1254.PubMedGoogle Scholar
  130. 130.
    Mena, A., Smith, E.E., Burns, J.L., Speert, D.P., Moskowitz, S.M., Perez, J.L. and Oliver., A. (2008) Genetic adaptation of Pseudomonas aeruginosa to the airways of cystic fibrosis patients is catalyzed by hypermutation. J. Bacteriol. 190: 7910–7917.PubMedGoogle Scholar
  131. 131.
    Treggiari, M.M., Rosenfeld, M., Retsch-Bogart, G., Gibson, R. and Ramsey., B. (2007) Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr. Pulmonol. 42: 751–756.PubMedGoogle Scholar
  132. 132.
    Frederiksen, B., Koch, C. and Hoiby., N. (1997) Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr. Pulmonol. 23: 330–335.PubMedGoogle Scholar
  133. 133.
    Jacobs, M.A., Alwood, A., Thaipisuttikul, I., Spencer, D., Haugen, E., Ernst, S., Will, O., Kaul, R., Raymond, C., Levy, R., Chun-Rong, L., Guenthner, D., Bovee, D., Olson, M.V. and Manoil., C. (2003) Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 100: 14339–14344.PubMedGoogle Scholar
  134. 134.
    Liberati, N.T., Urbach, J.M., Miyata, S., Lee, D.G., Drenkard, E., Wu, G., Villanueva, J., Wei, T. and Ausubel., F.M. (2006) An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc. Natl. Acad. Sci. USA 103: 2833–2838.PubMedGoogle Scholar
  135. 135.
    Lehoux, D.E., Sanschagrin, F. and Levesque., R.C. (2002) Identification of in vivo essential genes from Pseudomonas aeruginosa by PCR-based signature-tagged mutagenesis. FEMS Microbiol. Lett. 210: 73–80.PubMedGoogle Scholar
  136. 136.
    Mdluli, K.E., Witte, P.R., Kline, T., Barb, A.W., Erwin, A.L., Mansfield, B.E., McClerren, A.L., Pirrung, M.C., Tumey, L.N., Warrener, P., Raetz, C.R. and Stover., C.K. (2006) Molecular validation of LpxC as an antibacterial drug target in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 50: 2178–2184.PubMedGoogle Scholar
  137. 137.
    Paradis-Bleau, C., Lloyd, A., Sanschagrin, F., Clarke, T., Blewett, A., Bugg, T.D. and Levesque., R.C. (2008) Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF. BMC Biochem. 9: 33.PubMedGoogle Scholar
  138. 138.
    El Zoeiby, A., Sanschagrin, F., Darveau, A., Brisson, J.R. and Levesque., R.C. (2003) Identification of novel inhibitors of Pseudomonas aeruginosa MurC enzyme derived from phage-displayed peptide libraries. J. Antimicrob. Chemother. 51: 531–543.PubMedGoogle Scholar
  139. 139.
    Pennington, J.E., Reynolds, H.Y., Wood, R.E., Robinson, R.A. and Levine., A.S. (1975) Use of a Pseudomonas aeruginosa vaccine in patients with acute leukemia and cystic fibrosis. Am. J. Med. 58: 629–636.PubMedGoogle Scholar
  140. 140.
    Doring, G. and Pier., G.B. (2008) Vaccines and immunotherapy against Pseudomonas aeruginosa. Vaccine 26: 1011–1024.PubMedGoogle Scholar
  141. 141.
    Langford, D.T. and Hiller., J. (1984) Prospective, controlled study of a polyvalent Pseudomonas vaccine in cystic fibrosis–three year results. Arch. Dis. Child. 59: 1131–1134.PubMedGoogle Scholar
  142. 142.
    Cryz, S.J., Jr., Wedgwood, J., Lang, A.B., Ruedeberg, A., Que, J.U., Furer, E. and Schaad., U.B. (1994) Immunization of noncolonized cystic fibrosis patients against Pseudomonas aeruginosa. J. Infect. Dis. 169: 1159–1162.PubMedGoogle Scholar
  143. 143.
    Schaad, U.B., Lang, A.B., Wedgwood, J., Ruedeberg, A., Que, J.U., Furer, E. and Cryz, S.J., Jr. (1991) Safety and immunogenicity of Pseudomonas aeruginosa conjugate A vaccine in cystic fibrosis. Lancet 338: 1236–1237.PubMedGoogle Scholar
  144. 144.
    Lang, A.B., Rudeberg, A., Schoni, M.H., Que, J.U., Furer, E. and Schaad., U.B. (2004) Vaccination of cystic fibrosis patients against Pseudomonas aeruginosa reduces the proportion of patients infected and delays time to infection. Pediatr. Infect. Dis. J. 23: 504–510.PubMedGoogle Scholar
  145. 145.
    Doring, G., Meisner, C. and Stern., M. (2007) A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 104: 11020–11025.PubMedGoogle Scholar
  146. 146.
    Johansen, H.K. and Gotzsche, P.C. 2008. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis. Cochrane database of systematic reviews (Online):CD001399.Google Scholar
  147. 147.
    Pier, G.B., Small, G.J. and Warren., H.B. (1990) Protection against mucoid Pseudomonas aeruginosa in rodent models of endobronchial infections. Science 249: 537–540.PubMedGoogle Scholar
  148. 148.
    Pier, G. (2005) Application of vaccine technology to prevention of Pseudomonas aeruginosa infections. Expert Rev. Vaccines 4: 645–656.PubMedGoogle Scholar
  149. 149.
    Pier, G.B., Matthews, W.J., Jr. and Eardley., D.D. (1983) Immunochemical characterization of the mucoid exopolysaccharide of Pseudomonas aeruginosa. J. Infect. Dis. 147: 494–503.PubMedGoogle Scholar
  150. 150.
    Meluleni, G.J., Grout, M., Evans, D.J. and Pier., G.B. (1995) Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients. J. Immunol. 155: 2029–2038.PubMedGoogle Scholar
  151. 151.
    Pier, G.B., Boyer, D., Preston, M., Coleman, F.T., Llosa, N., Mueschenborn-Koglin, S., Theilacker, C., Goldenberg, H., Uchin, J., Priebe, G.P., Grout, M., Posner, M. and Cavacini., L. (2004) Human monoclonal antibodies to Pseudomonas aeruginosa alginate that protect against infection by both mucoid and nonmucoid strains. J. Immunol. 173: 5671–5678.PubMedGoogle Scholar
  152. 152.
    Singh, P.K., Parsek, M.R., Greenberg, E.P. and Welsh., M.J. (2002) A component of innate immunity prevents bacterial biofilm development. Nature 417: 552–555.PubMedGoogle Scholar
  153. 153.
    Barraud, N., Hassett, D.J., Hwang, S.H., Rice, S.A., Kjelleberg, S. and Webb., J.S. (2006) Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J. Bacteriol. 188: 7344–7353.PubMedGoogle Scholar
  154. 154.
    Banin, E., Brady, K.M. and Greenberg., E.P. (2006) Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl. Environ. Microbiol. 72: 2064–2069.PubMedGoogle Scholar
  155. 155.
    Kaneko, Y., Thoendel, M., Olakanmi, O., Britigan, B.E. and Singh., P.K. (2007) The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J. Clin. Invest. 117: 877–888.PubMedGoogle Scholar
  156. 156.
    Boles, B.R., Thoendel, M. and Singh., P.K. (2005) Rhamnolipids mediate detachment of Pseudomonas aeruginosa from biofilms. Mol. Microbiol. 57: 1210–1223.PubMedGoogle Scholar
  157. 157.
    Ratjen, F. (2008) Recent advances in cystic fibrosis. Paediatr. Respir. Rev. 9: 144–148.PubMedGoogle Scholar
  158. 158.
    Boucher, R.C. (2007) Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu. Rev. Med. 58: 157–170.PubMedGoogle Scholar
  159. 159.
    Flume, P.A., O‘Sullivan, B.P., Robinson, K.A., Goss, C.H., Mogayzel, P.J., Jr., Willey-Courand, D.B., Bujan, J., Finder, J., Lester, M., Quittell, L., Rosenblatt, R., Vender, R.L., Hazle, L., Sabadosa, K. and Marshall., B. (2007) Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am. J. Respir. Crit. Care Med. 176: 957–969.PubMedGoogle Scholar
  160. 160.
    Ratjen, F. (2007) New pulmonary therapies for cystic fibrosis. Curr. Opin. Pulm. Med. 13: 541–546.PubMedGoogle Scholar
  161. 161.
    Aris, R.M., Gilligan, P.H., Neuringer, I.P., Gott, K.K., Rea, J. and Yankaskas., J.R. (1997) The effects of panresistant bacteria in cystic fibrosis patients on lung transplant outcome. Am. J. Respir. Crit. Care Med. 155: 1699–1704.PubMedGoogle Scholar
  162. 162.
    Kanj, S.S., Tapson, V., Davis, R.D., Madden, J. and Browning., I. (1997) Infections in patients with cystic fibrosis following lung transplantation. Chest 112: 924–930.PubMedGoogle Scholar
  163. 163.
    Walter, S., Gudowius, P., Bosshammer, J., Romling, U., Weissbrodt, H., Schurmann, W., von der Hardt, H. and Tummler., B. (1997) Epidemiology of chronic Pseudomonas aeruginosa infections in the airways of lung transplant recipients with cystic fibrosis. Thorax 52: 318–321.PubMedGoogle Scholar
  164. 164.
    Bonvillain, R.W., Valentine, V.G., Lombard, G., LaPlace, S., Dhillon, G. and Wang., G. (2007) Post-operative infections in cystic fibrosis and non-cystic fibrosis patients after lung transplantation. J. Heart Lung Transplant. 26: 890–897.PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.University of VirginiaCharlottesvilleUSA

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