Pseudomonas aeruginosa: A Persistent Pathogen in Cystic Fibrosis and Hospital-Associated Infections

  • Kristen N. Schurek
  • Elena B. M. Breidenstein
  • Robert E. W. HancockEmail author


Over the past century, Pseudomonas aeruginosa has become an increasingly important pathogen, particularly in individuals with cystic fibrosis and in intensive care units worldwide. P. aeruginosa possesses a diverse array of virulence factors as well as high intrinsic resistance to many therapeutically-available antibiotics, lending to the characteristically high levels of lethality and persistence associated with P. aeruginosa infections. Furthermore, this bacterium has an unparalleled ability to adapt to the varying environments and stresses it encounters, as its large genome encodes numerous complex regulatory systems, and it readily acquires mobile genetic elements and plasmids. The finely tuned regulation of its virulence factors is best evidenced by the adaptations occurring during chronic cystic fibrosis infections, which contribute to the organism’s ability to evade attack by host immune responses and also limits killing by all available antibiotics. Despite the major role this organism plays within the hospital, few effective antimicrobial agents with adequate anti-pseudomonal activity have been developed and resistance to all available agents has been reported.


Cystic Fibrosis Cystic Fibrosis Patient Alkaline Protease Cystic Fibrosis Lung National Healthcare Safety Network 
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.



We would like to thank the Canadian Institutes of Health Research as well as Cystic Fibrosis Canada for supporting our work. Furthermore, K.N.S. holds a Natural Sciences and Engineering Council of Canada postgraduate scholarship and a Michael Smith Foundation for Health Research Senior graduate studentship. E.B.M.B. is a recipient of a scholarship from Cystic Fibrosis Canada. R.E.W.H. holds a Canada Research Chair.


  1. 1.
    Altoparlak U, Erol S, Akcay MN et al (2004) The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 30:660–664PubMedGoogle Scholar
  2. 2.
    Ambrose PG, Owens RC Jr, Garvey MJ et al (2002) Pharmacodynamic considerations in the treatment of moderate to severe pseudomonal infections with cefepime. J Antimicrob Chemother 49:445–453PubMedGoogle Scholar
  3. 3.
    Andriole VT (1971) Synergy of carbenicillin and gentamicin in experimental infection with Pseudomonas. J Infect Dis 124(Suppl):S46–S55PubMedGoogle Scholar
  4. 4.
    Arora SK, Ritchings BW, Almira EC et al (1998) The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect Immun 66:1000–1007PubMedGoogle Scholar
  5. 5.
    Backhed F, Normark S, Schweda EK et al (2003) Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications. Microbes Infect 5:1057–1063PubMedGoogle Scholar
  6. 6.
    Baker CC, Miller CL, Trunkey DD (1979) Predicting fatal sepsis in burn patients. J Trauma 19:641–648PubMedGoogle Scholar
  7. 7.
    Bals R, Weiner DJ, Wilson JM (1999) The innate immune system in cystic fibrosis lung disease. J Clin Invest 103:303–307PubMedGoogle Scholar
  8. 8.
    Bang RL, Sharma PN, Sanyal SC et al (2002) Septicaemia after burn injury: a comparative study. Burns 28:746–751PubMedGoogle Scholar
  9. 9.
    Barbieri JT, Sun J (2004) Pseudomonas aeruginosa ExoS and ExoT. Rev Physiol Biochem Pharmacol 152:79–92PubMedGoogle Scholar
  10. 10.
    Barclay ML, Begg EJ, Chambers ST et al (1996) Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis. J Antimicrob Chemother 37: 1155–1164PubMedGoogle Scholar
  11. 11.
    Barken KB, Pamp SJ, Yang L et al (2008) Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. Environ Microbiol 10:2331–2343PubMedGoogle Scholar
  12. 12.
    Barker AF, Couch L, Fiel SB et al (2000) Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 162:481–485PubMedGoogle Scholar
  13. 13.
    Barret JP, Herndon DN (2003) Effects of burn wound excision on bacterial colonization and invasion. Plast Reconstr Surg 111:744–750, Discussion 51–2PubMedGoogle Scholar
  14. 14.
    Barrow RE, Spies M, Barrow LN et al (2004) Influence of demographics and inhalation injury on burn mortality in children. Burns 30:72–77PubMedGoogle Scholar
  15. 15.
    Bellido F, Martin NL, Siehnel RJ et al (1992) Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability. J Bacteriol 174:5196–5203PubMedGoogle Scholar
  16. 16.
    Beno P, Krcmery V, Demitrovicova A (2006) Bacteraemia in cancer patients caused by colistin-resistant Gram-negative bacilli after previous exposure to ciprofloxacin and/or colistin. Clin Microbiol Infect 12:497–498PubMedGoogle Scholar
  17. 17.
    Blohmke CJ, Victor RE, Hirschfeld AF et al (2008) Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease. J Immunol 180:7764–7773PubMedGoogle Scholar
  18. 18.
    Blondel-Hill E, Fryters S (2006) Bugs and drugs. Capital Health, EdmontonGoogle Scholar
  19. 19.
    Bodey GP (1970) Epidemiological studies of Pseudomonas species in patients with leukemia. Am J Med Sci 260:82–89PubMedGoogle Scholar
  20. 20.
    Bodey GP, Whitecar JP Jr, Middleman E et al (1971) Carbenicillin therapy for pseudomonas infections. J Am Med Assoc 218:62–66Google Scholar
  21. 21.
    Bodey GP, Jadeja L, Elting L (1985) Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med 145:1621–1629PubMedGoogle Scholar
  22. 22.
    Boucher JC, Yu H, Mudd MH et al (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 65:3838–3846PubMedGoogle Scholar
  23. 23.
    Boucher JC, Schurr MJ, Yu H et al (1997) Pseudomonas aeruginosa in cystic fibrosis: role of mucC in the regulation of alginate production and stress sensitivity. Microbiology 143(Pt 11):3473–3480PubMedGoogle Scholar
  24. 24.
    Bradley DE (1980) A function of Pseudomonas aeruginosa PAO polar pili: twitching motility. Can J Microbiol 26:146–154PubMedGoogle Scholar
  25. 25.
    Brazas MD, Hancock REW (2005) Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:3222–3227PubMedGoogle Scholar
  26. 26.
    Breidenstein EBM, Khaira BK, Wiegand I et al (2008) Complex ciprofloxacin resistome revealed by screening a Pseudomonas aeruginosa mutant library for altered susceptibility. Antimicrob Agents Chemother 52:4486–4491PubMedGoogle Scholar
  27. 27.
    Brint JM, Ohman DE (1995) Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family. J Bacteriol 177:7155–7163PubMedGoogle Scholar
  28. 28.
    Brown MR, Allison DG, Gilbert P (1988) Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother 22:777–780PubMedGoogle Scholar
  29. 29.
    Canton R, Cobos N, de Gracia J et al (2005) Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect 11:690–703PubMedGoogle Scholar
  30. 30.
    Cardany CR, Rodeheaver GT, Horowitz JH et al (1985) Influence of hydrotherapy and antiseptic agents on burn wound bacterial contamination. J Burn Care Rehabil 6:230–232PubMedGoogle Scholar
  31. 31.
    Chamot E, Boffi El Amari E, Rohner P et al (2003) Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother 47: 2756–2764PubMedGoogle Scholar
  32. 32.
    Chastre J (2008) Evolving problems with resistant pathogens. Clin Microbiol Infect 14(Suppl 3): 3–14PubMedGoogle Scholar
  33. 33.
    Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903PubMedGoogle Scholar
  34. 34.
    Cheer SM, Waugh J, Noble S (2003) Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs 63:2501–2520PubMedGoogle Scholar
  35. 35.
    Choong S, Whitfield H (2000) Biofilms and their role in infections in urology. BJU Int 86: 935–941PubMedGoogle Scholar
  36. 36.
    Church D, Elsayed S, Reid O et al (2006) Burn wound infections. Clin Microbiol Rev 19: 403–434PubMedGoogle Scholar
  37. 37.
    Collins FS (1992) Cystic fibrosis: molecular biology and therapeutic implications. Science 256:774–779PubMedGoogle Scholar
  38. 38.
    Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322PubMedGoogle Scholar
  39. 39.
    Craig W (1993) Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. Eur J Clin Microbiol Infect Dis 12(Suppl 1):S6–S8PubMedGoogle Scholar
  40. 40.
    Cryz SJ Jr, Furer E, Germanier R (1983) Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice. Infect Immun 39:1067–1071PubMedGoogle Scholar
  41. 41.
    Dasgupta N, Wolfgang MC, Goodman AL et al (2003) A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol Microbiol 50:809–824PubMedGoogle Scholar
  42. 42.
    Davies JC (2002) Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev 3:128–134PubMedGoogle Scholar
  43. 43.
    Deretic V, Schurr MJ, Boucher JC et al (1994) Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis: environmental stress and regulation of bacterial virulence by alternative sigma factors. J Bacteriol 176:2773–2780PubMedGoogle Scholar
  44. 44.
    Dhand R (2007) The role of aerosolized antimicrobials in the treatment of ventilator-associated pneumonia. Respir Care 52:866–884PubMedGoogle Scholar
  45. 45.
    Diaz MH, Shaver CM, King JD et al (2008) Pseudomonas aeruginosa induces localized immunosuppression during pneumonia. Infect Immun 76:4414–4421PubMedGoogle Scholar
  46. 46.
    Diggle SP, Cornelis P, Williams P et al (2006) 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int J Med Microbiol 296:83–91PubMedGoogle Scholar
  47. 47.
    Doggett RG (1969) Incidence of mucoid Pseudomonas aeruginosa from clinical sources. Appl Microbiol 18:936–937PubMedGoogle Scholar
  48. 48.
    Doggett RG (1979) Microbiology of Pseudomonas aeruginosa. In: Doggett RG (ed) Pseudomonas aeruginosa: clinical manifestations of infection and current therapy. Academic, New YorkGoogle Scholar
  49. 49.
    Doggett RG, Harrison GM, Carter RE (1971) Mucoid Pseudomonas aeruginosa in patients with chronic illnesses. Lancet 1:236–237PubMedGoogle Scholar
  50. 50.
    Doi Y, Arakawa Y (2007) 16 S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis 45:88–94PubMedGoogle Scholar
  51. 51.
    Doring G, Pier GB (2008) Vaccines and immunotherapy against Pseudomonas aeruginosa. Vaccine 26:1011–1024PubMedGoogle Scholar
  52. 52.
    Doring G, Conway SP, Heijerman HG et al (2000) Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16:749–767PubMedGoogle Scholar
  53. 53.
    Drobnic ME, Sune P, Montoro JB et al (2005) Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother 39:39–44PubMedGoogle Scholar
  54. 54.
    Dropulic LK, Leslie JM, Eldred LJ et al (1995) Clinical manifestations and risk factors of Pseudomonas aeruginosa infection in patients with AIDS. J Infect Dis 171:930–937PubMedGoogle Scholar
  55. 55.
    Dudley MN, Zinner SH (1991) Single daily dosing of amikacin in an in-vitro model. J Antimicrob Chemother 27(Suppl C):15–19PubMedGoogle Scholar
  56. 56.
    El Solh AA, Akinnusi ME, Wiener-Kronish JP et al (2008) Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am J Respir Crit Care Med 178:513–519PubMedGoogle Scholar
  57. 57.
    Ernst RK, Yi EC, Guo L et al (1999) Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286:1561–1565PubMedGoogle Scholar
  58. 58.
    Ernst RK, Hajjar AM, Tsai JH et al (2003) Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4. J Endotoxin Res 9:395–400PubMedGoogle Scholar
  59. 59.
    Fagon JY, Chastre J, Hance AJ et al (1993) Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 94:281–288PubMedGoogle Scholar
  60. 60.
    Falagas ME, Siempos II, Bliziotis IA et al (2006) Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care 10:R123PubMedGoogle Scholar
  61. 61.
    Faure K, Fujimoto J, Shimabukuro DW et al (2003) Effects of monoclonal anti-PcrV antibody on Pseudomonas aeruginosa-induced acute lung injury in a rat model. J Immune Based Ther Vaccines 1:2PubMedGoogle Scholar
  62. 62.
    Feeley TW, Du Moulin GC, Hedley-Whyte J et al (1975) Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med 293:471–475PubMedGoogle Scholar
  63. 63.
    Fishman LS, Armstrong D (1972) Pseudomonas aeruginosa bacteremia in patients with neoplastic disease. Cancer 30:764–773PubMedGoogle Scholar
  64. 64.
    Frank DW (1997) The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Microbiol 26: 621–629PubMedGoogle Scholar
  65. 65.
    Frederiksen B, Koch C, 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 23:330–335PubMedGoogle Scholar
  66. 66.
    Friedman L, Kolter R (2004) Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol Microbiol 51:675–690PubMedGoogle Scholar
  67. 67.
    Fukuda H, Hosaka M, Iyobe S et al (1995) nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:790–792PubMedGoogle Scholar
  68. 68.
    Fuqua C, Greenberg EP (2002) Listening in on bacteria: acyl-homoserine lactone signalling. Nat Rev Mol Cell Biol 3:685–695PubMedGoogle Scholar
  69. 69.
    Gacesa P, Wusteman FS (1990) Plate assay for simultaneous detection of alginate lyases and determination of substrate specificity. Appl Environ Microbiol 56:2265–2267PubMedGoogle Scholar
  70. 70.
    Galloway DR (1991) Pseudomonas aeruginosa elastase and elastolysis revisited: recent developments. Mol Microbiol 5:2315–2321PubMedGoogle Scholar
  71. 71.
    Gang RK, Bang RL, Sanyal SC et al (1999) Pseudomonas aeruginosa septicaemia in burns. Burns 25:611–616PubMedGoogle Scholar
  72. 72.
    Gaynes R, Edwards JR (2005) Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 41:848–854PubMedGoogle Scholar
  73. 73.
    Gibson RL, Burns JL, Ramsey BW (2003) Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 168:918–951PubMedGoogle Scholar
  74. 74.
    Gibson RL, Emerson J, McNamara S et al (2003) Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med 167:841–849PubMedGoogle Scholar
  75. 75.
    Gilleland LB, Gilleland HE, Gibson JA et al (1989) Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa. J Med Microbiol 29:41–50PubMedGoogle Scholar
  76. 76.
    Goranson J, Hovey AK, Frank DW (1997) Functional analysis of exsC and exsB in regulation of exoenzyme S production by Pseudomonas aeruginosa. J Bacteriol 179:1646–1654PubMedGoogle Scholar
  77. 77.
    Gotoh N, Itoh N, Tsujimoto H et al (1994) Isolation of OprM-deficient mutants of Pseudomonas aeruginosa by transposon insertion mutagenesis: evidence of involvement in multiple antibiotic resistance. FEMS Microbiol Lett 122:267–273PubMedGoogle Scholar
  78. 78.
    Govan JR, Deretic V (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 60:539–574PubMedGoogle Scholar
  79. 79.
    Grassme H, Jendrossek V, Riehle A et al (2003) Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat Med 9:322–330PubMedGoogle Scholar
  80. 80.
    Grimwood K (1992) The pathogenesis of Pseudomonas aeruginosa lung infections in cystic fibrosis. J Paediatr Child Health 28:4–11PubMedGoogle Scholar
  81. 81.
    Hahn HP (1997) The type-4 pilus is the major virulence-associated adhesin of Pseudomonas aeruginosa–a review. Gene 192:99–108PubMedGoogle Scholar
  82. 82.
    Hancock REW (1997) The bacterial outer membrane as a drug barrier. Trends Microbiol 5:37–42PubMedGoogle Scholar
  83. 83.
    Hancock REW (1998) Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin Infect Dis 27(Suppl 1):S93–S99PubMedGoogle Scholar
  84. 84.
    Hancock REW, Woodruff WA (1988) Roles of porin and beta-lactamase in beta-lactam resistance of Pseudomonas aeruginosa. Rev Infect Dis 10:770–775PubMedGoogle Scholar
  85. 85.
    Hancock REW, Raffle VJ, Nicas TI (1981) Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 19:777–785PubMedGoogle Scholar
  86. 86.
    Hancock REW, Mutharia LM, Chan L et al (1983) Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun 42:170–177PubMedGoogle Scholar
  87. 87.
    Hanessian S, Regan W, Watson D et al (1971) Isolation and characterization of antigenic components of a new heptavalent Pseudomonas vaccine. Nat New Biol 229:209–210PubMedGoogle Scholar
  88. 88.
    Hansen JK, Forest KT (2006) Type IV pilin structures: insights on shared architecture, fiber assembly, receptor binding and type II secretion. J Mol Microbiol Biotechnol 11:192–207PubMedGoogle Scholar
  89. 89.
    Hansen M, Christrup LL, Jarlov JO et al (2001) Gentamicin dosing in critically ill patients. Acta Anaesthesiol Scand 45:734–740PubMedGoogle Scholar
  90. 90.
    Hauser AR, Cobb E, Bodi M et al (2002) Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 30:521–528PubMedGoogle Scholar
  91. 91.
    Haussler S, Ziegler I, Lottel A et al (2003) Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. J Med Microbiol 52:295–301PubMedGoogle Scholar
  92. 92.
    Heine H, Rietschel ET, Ulmer AJ (2001) The biology of endotoxin. Mol Biotechnol 19:279–296PubMedGoogle Scholar
  93. 93.
    Henrichfreise B, Wiegand I, Pfister W et al (2007) Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob Agents Chemother 51:4062–4070PubMedGoogle Scholar
  94. 94.
    Heurlier K, Williams F, Heeb S et al (2004) Positive control of swarming, rhamnolipid synthesis, and lipase production by the posttranscriptional RsmA/RsmZ system in Pseudomonas aeruginosa PAO1. J Bacteriol 186:2936–2945PubMedGoogle Scholar
  95. 95.
    Hidron AI, Edwards JR, Patel J et al (2008) NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 29:996–1011PubMedGoogle Scholar
  96. 96.
    Hilf M, Yu VL, Sharp J et al (1989) Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 87:540–546PubMedGoogle Scholar
  97. 97.
    Hodson ME (2000) Treatment of cystic fibrosis in the adult. Respiration 67:595–607PubMedGoogle Scholar
  98. 98.
    Hodson ME, Penketh AR, Batten JC (1981) Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Lancet 2:1137–1139PubMedGoogle Scholar
  99. 99.
    Hoffmann N, Rasmussen TB, Jensen PO et al (2005) Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect Immun 73: 2504–2514PubMedGoogle Scholar
  100. 100.
    Hoffmann N, Lee B, Hentzer M et al (2007) Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudomonas aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr(−/−) mice. Antimicrob Agents Chemother 51:3677–3687PubMedGoogle Scholar
  101. 101.
    Hogardt M, Hoboth C, Schmoldt S et al (2007) Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 195:70–80PubMedGoogle Scholar
  102. 102.
    Hoiby N (1998) Pseudomonas in cystic fibrosis: past, present, and future. Cystic Fibrosis Trust, LondonGoogle Scholar
  103. 103.
    Hollsing AE, Granstrom M, Vasil ML et al (1987) Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis. J Clin Microbiol 25:1868–1874PubMedGoogle Scholar
  104. 104.
    Holmes KK, Clark H, Silverblatt F et al (1969) Emergence of resistance in Pseudomonas during carbenicillin therapy. Antimicrob Agents Chemother (Bethesda) 9:391–397Google Scholar
  105. 105.
    Hoyle BD, Costerton JW (1991) Bacterial resistance to antibiotics: the role of biofilms. Prog Drug Res 37:91–105PubMedGoogle Scholar
  106. 106.
    Hoyle BD, Jass J, Costerton JW (1990) The biofilm glycocalyx as a resistance factor. J Antimicrob Chemother 26:1–5PubMedGoogle Scholar
  107. 107.
    Huang H, Hancock REW (1993) Genetic definition of the substrate selectivity of outer membrane porin protein OprD of Pseudomonas aeruginosa. J Bacteriol 175:7793–7800PubMedGoogle Scholar
  108. 108.
    Huang H, Hancock REW (1996) The role of specific surface loop regions in determining the function of the imipenem-specific pore protein OprD of Pseudomonas aeruginosa. J Bacteriol 178:3085–3090PubMedGoogle Scholar
  109. 109.
    Hudson VL, Wielinski CL, Regelmann WE (1993) Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. J Pediatr 122:854–860PubMedGoogle Scholar
  110. 110.
    Jagger KS, Robinson DL, Franz MN et al (1982) Detection by enzyme-linked immunosorbent assays of antibody specific for Pseudomonas proteases and exotoxin A in sera from cystic fibrosis patients. J Clin Microbiol 15:1054–1058PubMedGoogle Scholar
  111. 111.
    Jalal S, Wretlind B (1998) Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. Microb Drug Resist 4:257–261PubMedGoogle Scholar
  112. 112.
    Jo JT, Brinkman FS, Hancock REW (2003) Aminoglycoside efflux in Pseudomonas aeruginosa: involvement of novel outer membrane proteins. Antimicrob Agents Chemother 47: 1101–1111PubMedGoogle Scholar
  113. 113.
    Khoury AE, Lam K, Ellis B et al (1992) Prevention and control of bacterial infections associated with medical devices. ASAIO J 38:M174–M178PubMedGoogle Scholar
  114. 114.
    Kirisits MJ, Prost L, Starkey M et al (2005) Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 71:4809–4821PubMedGoogle Scholar
  115. 115.
    Klausen M, Aaes-Jorgensen A, Molin S et al (2003) Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50:61–68PubMedGoogle Scholar
  116. 116.
    Klausen M, Heydorn A, Ragas P et al (2003) Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol Microbiol 48:1511–1524PubMedGoogle Scholar
  117. 117.
    Knirel YA, Bystrova OV, Shashkov AS et al (2001) Structural analysis of the lipopolysaccharide core of a rough, cystic fibrosis isolate of Pseudomonas aeruginosa. Eur J Biochem 268:4708–4719PubMedGoogle Scholar
  118. 118.
    Knirel YA, Bystrova OV, Kocharova NA et al (2006) Conserved and variable structural features in the lipopolysaccharide of Pseudomonas aeruginosa. J Endotoxin Res 12:324–336PubMedGoogle Scholar
  119. 119.
    Kobayashi M, Yoshida T, Takeuchi D et al (2008) Gr-1(+)CD11b(+) cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice. J Leukoc Biol 83:1354–1362PubMedGoogle Scholar
  120. 120.
    Kohler T, Michea-Hamzehpour M, Plesiat P et al (1997) Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 41:2540–2543PubMedGoogle Scholar
  121. 121.
    Kohler T, Curty LK, Barja F et al (2000) Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996PubMedGoogle Scholar
  122. 122.
    Kurahashi K, Kajikawa O, Sawa T et al (1999) Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 104:743–750PubMedGoogle Scholar
  123. 123.
    Kus JV, Tullis E, Cvitkovitch DG et al (2004) Significant differences in type IV pilin allele distribution among Pseudomonas aeruginosa isolates from cystic fibrosis (CF) versus non-CF patients. Microbiology 150:1315–1326PubMedGoogle Scholar
  124. 124.
    Lam JS, Lam MY, MacDonald LA et al (1987) Visualization of Pseudomonas aeruginosa O antigens by using a protein A-dextran-colloidal gold conjugate with both immunoglobulin G and immunoglobulin M monoclonal antibodies. J Bacteriol 169:3531–3538PubMedGoogle Scholar
  125. 125.
    Langaee TY, Dargis M, Huletsky A (1998) An ampD gene in Pseudomonas aeruginosa encodes a negative regulator of AmpC beta-lactamase expression. Antimicrob Agents Chemother 42:3296–3300PubMedGoogle Scholar
  126. 126.
    Langford DT, Hiller J (1984) Prospective, controlled study of a polyvalent Pseudomonas vaccine in cystic fibrosis–three year results. Arch Dis Child 59:1131–1134PubMedGoogle Scholar
  127. 127.
    Le Conte P, Potel G, Peltier P et al (1993) Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis 147:1279–1282PubMedGoogle Scholar
  128. 128.
    Leibovici L, Paul M (2007) Aminoglycoside/beta-lactam combinations in clinical practice. J Antimicrob Chemother 60:911–912PubMedGoogle Scholar
  129. 129.
    Leibovici L, Paul M, Poznanski O et al (1997) Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study. Antimicrob Agents Chemother 41:1127–1133PubMedGoogle Scholar
  130. 130.
    Li XZ, Nikaido H, Poole K (1995) Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:1948–1953PubMedGoogle Scholar
  131. 131.
    Littlewood JM, Miller MG, Ghoneim AT et al (1985) Nebulised colomycin for early pseudomonas colonisation in cystic fibrosis. Lancet 1:865PubMedGoogle Scholar
  132. 132.
    Liu PV, Wang S (1990) Three new major somatic antigens of Pseudomonas aeruginosa. J Clin Microbiol 28:922–925PubMedGoogle Scholar
  133. 133.
    Livermore DM (1987) Clinical significance of beta-lactamase induction and stable derepression in gram-negative rods. Eur J Clin Microbiol 6:439–445PubMedGoogle Scholar
  134. 134.
    Llanes C, Hocquet D, Vogne C et al (2004) Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob Agents Chemother 48:1797–1802PubMedGoogle Scholar
  135. 135.
    Lodge J, Busby S, Piddock L (1993) Investigation of the Pseudomonas aeruginosa ampR gene and its role at the chromosomal ampC beta-lactamase promoter. FEMS Microbiol Lett 111:315–320PubMedGoogle Scholar
  136. 136.
    MacMillan BG (1980) Infections following burn injury. Surg Clin North Am 60:185–196PubMedGoogle Scholar
  137. 137.
    Mah TF, Pitts B, Pellock B et al (2003) A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426:306–310PubMedGoogle Scholar
  138. 138.
    Masuda N, Sakagawa E, Ohya S (1995) Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:645–649PubMedGoogle Scholar
  139. 139.
    Masuda N, Sakagawa E, Ohya S et al (2000) Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:3322–3327PubMedGoogle Scholar
  140. 140.
    Masuda N, Sakagawa E, Ohya S et al (2000) Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:2242–2246PubMedGoogle Scholar
  141. 141.
    McCall CY, Spruill WJ, Wade WE (1989) The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis. Ther Drug Monit 11:692–695PubMedGoogle Scholar
  142. 142.
    McCoy KS, Quittner AL, Oermann CM et al (2008) Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med 178: 921–928PubMedGoogle Scholar
  143. 143.
    Morrison AJ Jr, Wenzel RP (1984) Epidemiology of infections due to Pseudomonas aeruginosa. Rev Infect Dis 6(Suppl 3):S627–S642PubMedGoogle Scholar
  144. 144.
    Moskowitz SM, Ernst RK, Miller SI (2004) PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 186:575–579PubMedGoogle Scholar
  145. 145.
    Nicas TI, Hancock REW (1983) Alteration of susceptibility to EDTA, polymyxin B and gentamicin in Pseudomonas aeruginosa by divalent cation regulation of outer membrane protein H1. J Gen Microbiol 129:509–517PubMedGoogle Scholar
  146. 146.
    Nikaido H (2001) Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria. Semin Cell Dev Biol 12:215–223PubMedGoogle Scholar
  147. 147.
    Nikaido H, Nikaido K, Harayama S (1991) Identification and characterization of porins in Pseudomonas aeruginosa. J Biol Chem 266:770–779PubMedGoogle Scholar
  148. 148.
    Nixon GM, Armstrong DS, Carzino R et al (2001) Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J Pediatr 138:699–704PubMedGoogle Scholar
  149. 149.
    NNIS (2004) National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 32:470–485Google Scholar
  150. 150.
    Ochs MM, McCusker MP, Bains M et al (1999) Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids. Antimicrob Agents Chemother 43:1085–1090PubMedGoogle Scholar
  151. 151.
    Oliver A, Canton R, Campo P et al (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254PubMedGoogle Scholar
  152. 152.
    Orriols R, Roig J, Ferrer J et al (1999) Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa. Respir Med 93:476–480PubMedGoogle Scholar
  153. 153.
    Pai H, Kim J, Lee JH et al (2001) Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 45:480–484PubMedGoogle Scholar
  154. 154.
    Palmer LB, Smaldone GC, Simon SR et al (1998) Aerosolized antibiotics in mechanically ventilated patients: delivery and response. Crit Care Med 26:31–39PubMedGoogle Scholar
  155. 155.
    Passador L, Iglewski W (1994) ADP-ribosylating toxins. Methods Enzymol 235:617–631PubMedGoogle Scholar
  156. 156.
    Paul M, Leibovici L (2005) Combination antibiotic therapy for Pseudomonas aeruginosa bacteraemia. Lancet Infect Dis 5:192–193, Discussion 3–4PubMedGoogle Scholar
  157. 157.
    Pennington JE (1979) Lipopolysaccharide Pseudomonas vaccine: efficacy against pulmonary infection with Pseudomonas aeruginosa. J Infect Dis 140:73–80PubMedGoogle Scholar
  158. 158.
    Pennington JE (1981) Penetration of antibiotics into respiratory secretions. Rev Infect Dis 3:67–73PubMedGoogle Scholar
  159. 159.
    Pennington JE, Miler JJ (1979) Evaluation of a new polyvalent Pseudomonas vaccine in respiratory infections. Infect Immun 25:1029–1034PubMedGoogle Scholar
  160. 160.
    Pier GB (2007) Pseudomonas aeruginosa lipopolysaccharide: a major virulence factor, initiator of inflammation and target for effective immunity. Int J Med Microbiol 297:277–295PubMedGoogle Scholar
  161. 161.
    Pier GB, Ames P (1984) Mediation of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement. J Infect Dis 150:223–228PubMedGoogle Scholar
  162. 162.
    Pier GB, Ramphal R (2005) Pseudomonas aeruginosa. In: Mandell GL, Bennett JE (eds) Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Elsevier/Churchill Livingstone, New YorkGoogle Scholar
  163. 163.
    Pier GB, Coleman F, Grout M et al (2001) Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis. Infect Immun 69:1895–1901PubMedGoogle Scholar
  164. 164.
    Poole K, Gotoh N, Tsujimoto H et al (1996) Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 21:713–724PubMedGoogle Scholar
  165. 165.
    Punsalang AP Jr, Sawyer WD (1973) Role of pili in the virulence of Neisseria gonorrhoeae. Infect Immun 8:255–263PubMedGoogle Scholar
  166. 166.
    Ramphal R, Guay C, Pier GB (1987) Pseudomonas aeruginosa adhesins for tracheobronchial mucin. Infect Immun 55:600–603PubMedGoogle Scholar
  167. 167.
    Ramsey BW, Pepe MS, Quan JM et al (1999) Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic fibrosis inhaled tobramycin study group. N Engl J Med 340:23–30PubMedGoogle Scholar
  168. 168.
    Rasmussen TB, Givskov M (2006) Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296:149–161PubMedGoogle Scholar
  169. 169.
    Ratjen F, Doring G (2003) Cystic fibrosis. Lancet 361:681–689PubMedGoogle Scholar
  170. 170.
    Ratjen F, Doring G, Nikolaizik WH (2001) Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet 358:983–984PubMedGoogle Scholar
  171. 171.
    Ratjen F, Comes G, Paul K et al (2001) Effect of continuous antistaphylococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis. Pediatr Pulmonol 31: 13–16PubMedGoogle Scholar
  172. 172.
    Reimmann C, Beyeler M, Latifi A et al (1997) The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24:309–319PubMedGoogle Scholar
  173. 173.
    Rello J, Ausina V, Ricart M et al (1993) Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 104:1230–1235PubMedGoogle Scholar
  174. 174.
    Richmond MH, Sykes RB (1973) The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol 9:31–88PubMedGoogle Scholar
  175. 175.
    Rosenfeld M, Ramsey BW, Gibson RL (2003) Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Curr Opin Pulm Med 9:492–497PubMedGoogle Scholar
  176. 176.
    Ryder C, Byrd M, Wozniak DJ (2007) Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr Opin Microbiol 10:644–648PubMedGoogle Scholar
  177. 177.
    Sabath LD (1984) Biochemical and physiologic basis for susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents. Rev Infect Dis 6(Suppl 3):S643–S656PubMedGoogle Scholar
  178. 178.
    Sacha P, Wieczorek P, Hauschild T et al (2008) Metallo-beta-lactamases of Pseudomonas aeruginosa–a novel mechanism resistance to beta-lactam antibiotics. Folia Histochem Cytobiol 46:137–142PubMedGoogle Scholar
  179. 179.
    Saiman L, Marshall BC, Mayer-Hamblett N et al (2003) Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. J Am Med Assoc 290:1749–1756Google Scholar
  180. 180.
    Salunkhe P, Smart CH, Morgan JA et al (2005) A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol 187:4908–4920PubMedGoogle Scholar
  181. 181.
    Sanders CC (1992) Beta-lactamases of gram-negative bacteria: new challenges for new drugs. Clin Infect Dis 14:1089–1099PubMedGoogle Scholar
  182. 182.
    Sato H, Frank DW (2004) ExoU is a potent intracellular phospholipase. Mol Microbiol 53:1279–1290PubMedGoogle Scholar
  183. 183.
    Sauer K, Camper AK, Ehrlich GD et al (2002) Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184:1140–1154PubMedGoogle Scholar
  184. 184.
    Schimpff S, Satterlee W, Young VM et al (1971) Empiric therapy with carbenicillin and ­gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med 284: 1061–1065PubMedGoogle Scholar
  185. 185.
    Schultz MJ, Rijneveld AW, Florquin S et al (2002) Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol 282:L285–L290PubMedGoogle Scholar
  186. 186.
    Schurek KN, Marr AK, Taylor PK et al (2008) Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 52: 4213–4219PubMedGoogle Scholar
  187. 187.
    Scott RE, Robson HG (1976) Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antimicrob Agents Chemother 10: 646–651PubMedGoogle Scholar
  188. 188.
    Shaw KJ, Rather PN, Hare RS et al (1993) Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 57:138–163PubMedGoogle Scholar
  189. 189.
    Shawar RM, MacLeod DL, Garber RL et al (1999) Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 43:2877–2880PubMedGoogle Scholar
  190. 190.
    Shime N, Sawa T, Fujimoto J et al (2001) Therapeutic administration of anti-PcrV F(ab′)(2) in sepsis associated with Pseudomonas aeruginosa. J Immunol 167:5880–5886PubMedGoogle Scholar
  191. 191.
    Singh PK, Schaefer AL, Parsek MR et al (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764PubMedGoogle Scholar
  192. 192.
    Smith AL, Doershuk C, Goldmann D et al (1999) Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis. J Pediatr 134:413–421PubMedGoogle Scholar
  193. 193.
    Smith RS, Harris SG, Phipps R et al (2002) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 184:1132–1139PubMedGoogle Scholar
  194. 194.
    Sorensen VJ, Horst HM, Obeid FN et al (1986) Endotracheal aminoglycosides in gram negative pneumonia. A preliminary report. Am Surg 52:391–394PubMedGoogle Scholar
  195. 195.
    Souli M, Galani I, Giamarellou H (2008) Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe. Euro Surveill 13 (47) pii:19045Google Scholar
  196. 196.
    Spoering AL, Lewis K (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 183:6746–6751PubMedGoogle Scholar
  197. 197.
    Starner TD, McCray PB Jr (2005) Pathogenesis of early lung disease in cystic fibrosis: a window of opportunity to eradicate bacteria. Ann Intern Med 143:816–822PubMedGoogle Scholar
  198. 198.
    Stead RJ, Hodson ME, Batten JC (1987) Inhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa. Br J Dis Chest 81:272–279PubMedGoogle Scholar
  199. 199.
    Steinkamp G, Tummler B, Gappa M et al (1989) Long-term tobramycin aerosol therapy in cystic fibrosis. Pediatr Pulmonol 6:91–98PubMedGoogle Scholar
  200. 200.
    Stieritz DD, Holder IA (1975) Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: description of a burned mouse model. J Infect Dis 131:688–691PubMedGoogle Scholar
  201. 201.
    Stillwell PC, Kearns GL, Jacobs RF (1988) Endotracheal tobramycin in gram-negative pneumonitis. Drug Intell Clin Pharm 22:577–581PubMedGoogle Scholar
  202. 202.
    Stoutenbeek CP, van Saene HK, Miranda DR et al (1986) Nosocomial gram-negative pneumonia in critically ill patients. A 3-year experience with a novel therapeutic regimen. Intensive Care Med 12:419–423PubMedGoogle Scholar
  203. 203.
    Stover CK, Pham XQ, Erwin AL et al (2000) Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406:959–964PubMedGoogle Scholar
  204. 204.
    Sykes RB, Matthew M (1976) The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics. J Antimicrob Chemother 2:115–157PubMedGoogle Scholar
  205. 205.
    Taccetti G, Campana S, Festini F et al (2005) Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients. Eur Respir J 26:458–461PubMedGoogle Scholar
  206. 206.
    Takada H, Kotani S (1989) Structural requirements of lipid A for endotoxicity and other biological activities. Crit Rev Microbiol 16:477–523PubMedGoogle Scholar
  207. 207.
    Tart AH, Wolfgang MC, Wozniak DJ (2005) The alternative sigma factor AlgT represses Pseudomonas aeruginosa flagellum biosynthesis by inhibiting expression of fleQ. J Bacteriol 187:7955–7962PubMedGoogle Scholar
  208. 208.
    Tateda K, Comte R, Pechere JC et al (2001) Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 45:1930–1933PubMedGoogle Scholar
  209. 209.
    Tateda K, Standiford TJ, Pechere JC et al (2004) Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors. Curr Pharm Des 10:3055–3065PubMedGoogle Scholar
  210. 210.
    Trafny EA (1998) Susceptibility of adherent organisms from Pseudomonas aeruginosa and Staphylococcus aureus strains isolated from burn wounds to antimicrobial agents. Int J Antimicrob Agents 10:223–228PubMedGoogle Scholar
  211. 211.
    Treggiari MM, Rosenfeld M, Retsch-Bogart G et al (2007) Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr Pulmonol 42:751–756PubMedGoogle Scholar
  212. 212.
    Valcke Y, Pauwels R, Van der Straeten M (1990) Pharmacokinetics of antibiotics in the lungs. Eur Respir J 3:715–722PubMedGoogle Scholar
  213. 213.
    Valerius NH, Koch C, Hoiby N (1991) Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 338:725–726PubMedGoogle Scholar
  214. 214.
    van Hartingsveldt J, Stouthamer AH (1973) Mapping and characerization of mutants of Pseudomonas aeruginosa affected in nitrate respiration in aerobic or anaerobic growth. J Gen Microbiol 74:97–106PubMedGoogle Scholar
  215. 215.
    Verhagen C, de Pauw BE, Donnelly JP et al (1986) Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients. J Infect 13:125–131PubMedGoogle Scholar
  216. 216.
    Verma A, Arora SK, Kuravi SK et al (2005) Roles of specific amino acids in the N terminus of Pseudomonas aeruginosa flagellin and of flagellin glycosylation in the innate immune response. Infect Immun 73:8237–8246PubMedGoogle Scholar
  217. 217.
    Westbrock-Wadman S, Sherman DR, Hickey MJ et al (1999) Characterization of a Pseudomonas aeruginosa efflux pump contributing to aminoglycoside impermeability. Antimicrob Agents Chemother 43:2975–2983PubMedGoogle Scholar
  218. 218.
    Whitecar JP Jr, Luna M, Bodey GP (1970) Pseudomonas bacteremia in patients with malignant diseases. Am J Med Sci 60:216–223PubMedGoogle Scholar
  219. 219.
    Winstanley C, Fothergill JL (2009) The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections. FEMS Microbiol Lett 290:1–9PubMedGoogle Scholar
  220. 220.
    Yahr TL, Mende-Mueller LM, Friese MB et al (1997) Identification of type III secreted products of the Pseudomonas aeruginosa exoenzyme S regulon. J Bacteriol 179:7165–7168PubMedGoogle Scholar
  221. 221.
    Yahr TL, Vallis AJ, Hancock MK et al (1998) ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginosa type III system. Proc Natl Acad Sci USA 95:13899–13904PubMedGoogle Scholar
  222. 222.
    Zhuo H, Yang K, Lynch SV et al (2008) Increased mortality of ventilated patients with endotracheal Pseudomonas aeruginosa without clinical signs of infection. Crit Care Med 36: 2495–2503PubMedGoogle Scholar
  223. 223.
    Ziha-Zarifi I, Llanes C, Kohler T et al (1999) In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob Agents Chemother 43:287–291PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kristen N. Schurek
    • 1
  • Elena B. M. Breidenstein
    • 1
  • Robert E. W. Hancock
    • 1
    Email author
  1. 1.Centre for Microbial Diseases and Immunity Research, Department of Microbiology and ImmunologyUniversity of British ColumbiaVancouverCanada

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