Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease

FEMS Microbiology Reviews

Volumn 35, Issue 1, 2011, Pages 124-146

  Doring, Gerd ^a   Parameswaran, Iyer G ^b   Murphy, Timothy F ^b  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b UNIVERSITY AT BUFFALO   (United States)

Author keywords

Adaptive radiation; Burkholderia ssp.; Haemophilus influenzae; Mutator; Pseudomonas aeruginosa; Staphylococcus aureus

Indexed keywords

AMITRIPTYLINE; CEFTAZIDIME; CIPROFLOXACIN; COLISTIN; DEOXYRIBONUCLEASE; ERYTHROMYCIN; RECOMBINANT ENZYME; TOBRAMYCIN;

ANTIBIOTIC THERAPY; ARTICLE; BACTERIAL COLONIZATION; BACTERIUM ADHERENCE; BACTERIUM COLONY; BURKHOLDERIA CEPACIA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; CYSTIC FIBROSIS; DISEASE EXACERBATION; DRUG ACTIVITY; ESCHERICHIA COLI; GENE MUTATION; HAEMOPHILUS INFLUENZAE; HUMAN; LUNG INFECTION; MORAXELLA CATARRHALIS; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTION; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE;

ADAPTATION, BIOLOGICAL; BACTERIA; BACTERIAL INFECTIONS; BACTERIAL PHYSIOLOGICAL PHENOMENA; CHRONIC DISEASE; CYSTIC FIBROSIS; HUMANS; PNEUMONIA, BACTERIAL; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RESPIRATORY TRACT INFECTIONS; STRESS, PHYSIOLOGICAL;

BACTERIA (MICROORGANISMS); BURKHOLDERIA; HAEMOPHILUS INFLUENZAE; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS;

EID: 78650018649     PISSN: 01686445     EISSN: 15746976     Source Type: Journal    
DOI: 10.1111/j.1574-6976.2010.00237.x     Document Type: Article

References (216)

1. Andersen DH (1938) Cystic fibrosis of the pancrease and its relation to coelic disease. Am J Dis Child 56: 344-399.
2. Anthonisen NR (2002) Bacteria and exacerbations of chronic obstructive pulmonary disease. New Engl J Med 347: 526-527.
3. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK & Nelson NA (1987) Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 106: 196-204.
4. Anthony M, Rose B, Pegler MB et al. (2002) Genetic analysis of Pseudomonas aeruginosa isolates from the sputa of Australian adult cystic fibrosis patients. J Clin Microbiol 40: 2772-2778.
5. Baird RM, Brown H, Smith AW & Watson ML (1999) Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells. Immunopharmacol 44: 267-272.
6. Barasch J, Kiss B, Prince A, Saiman L, Gruenert D & Al-Awqati Q (1991) Defective acidification of intracellular organelles in CF. Nature 352: 70-73.
7. Barnes PJ (2000) Chronic obstructive pulmonary disease. New Engl J Med 343: 269-280.
8. Barnes PJ (2004) Alveolar macrophages as orchestrators of COPD. COPD 1: 59-70.
9. Barnes PJ, Shapiro SD & Pauwels RA (2003) Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 22: 672-688.
10. Berenson CS, Garlipp MA, Grove LJ, Maloney J & Sethi S (2006a) Impaired phagocytosis of nontypeable Haemophilus influenzae by human alveolar macrophages in chronic obstructive pulmonary disease. J Infect Dis 194: 1375-1384.
11. Berenson CS, Wrona CT, Grove LJ et al. (2006b) Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am J Resp Crit Care 174: 31-40.
12. Berger M, Sorensen RU, Tosi MF, Dearborn DG & Döring G (1989) Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis. J Clin Invest 84: 1302-1313.
13. Biswas L, Biswas R, Schlag M, Bertram R & Gotz F (2009) Small-colony variant selection as a survival strategy for Staphylococcus aureus in the presence of Pseudomonas aeruginosa. Appl Environ Microb 75: 6910-6912.
14. Bittar F, Riichet H, Dubus J-C et al. (2008) Molecular detection of multiple emerging pathogens in sputa from cystic fibrosis patients. Plos ONE 3: e2908.
15. Black P, Staykova T, Chacko E, Ram FS & Poole P (2003) Prophylactic antibiotic therapy for chronic bronchitis. Cochrane Db Syst Rev 1: CD004105.
16. Boles BR & Horswill AR (2008) Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog 4: e1000052.
17. Boles BR, Thoendel M & Singh PK (2004) Self-generated diversity produces 'insurance effects' in biofilm communities. P Natl Acad Sci USA 101: 16630-16635.
18. Boucher JC, Yu H, Mudd MH & 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.
19. Boucher RC (2007) Airway surface dehydration in CF: pathogenesis and therapy. Annu Rev Med 58: 157-170.
20. Bragonzi A, Wiehlmann L, Klockgether J, Cramer N, Worlitzsch D, Döring G & Tümmler B (2006) Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 152: 3261-3269.
21. Bragonzi A, Paroni M, Nonis A, Cramer N, Montanari A, Rejman J, Di Serio C, Döring G & Tümmler B (2009) Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am J Resp Crit Care Dis 180: 138-145.
22. Brook I & Fink R (1983) Transtracheal aspiration in pulmonary infection in children with cystic fibrosis. Eur J Respir Dis 64: 51-57.
23. Burns JL (2005) Hypermutability in CF pathogens. Pediatr Pulm Suppl 28: 115-116.
24. Celli BR & MacNee W (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 23: 932-946.
25. Chin CL, Manzel LJ, Lehman EE et al. (2005) Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers. Am J Resp Crit Care 172: 85-91.
26. Chu KK, Davidson DJ, Halsey TK, Chung JW & Speert DP (2002) Differential persistence among genomovars of the Burkholderia cepacia complex in a murine model of pulmonary infection. Infect Immun 70: 2715-2720.
27. Ciofu O, Riis B, Pressler T, Poulsen HE & Høiby N (2005) Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation. Antimicrob Agents Ch 49: 2276-2282.
28. Ciofu O, Lee B, Johannesson M, Hermansen NO, Meyer P & Hoiby N for the Scandinavian Cystic Fibrosis Study Consortium (2008) Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants. Microbiology 154: 103-113.
29. Ciofu O, Mandsberg LF, Bjarnsholt T, Wassermann T & Høiby N (2010) 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 154: 1003-1013.
30. Coenye T, Vandamme P, Govan JR & LiPuma JJ (2001) Taxonomy and identification of the Burkholderia cepacia complex. J Clin Microbiol 39: 3427-3436.
31. Conway BA, Venu V & Speert DP (2002) Biofilm formation and acyl homoserine lactone production in the Burkholderia cepacia complex. J Bacteriol 184: 5678-5685.
32. Corey M & Farewell V (1996) Determinants of mortality from cystic fibrosis in Canada. Am J Epidemiol 43: 1007-1017.
33. Cornelis P, Matthijs S & Van Oeffelen L (2009) Iron uptake regulation in Pseudomonas aeruginosa. BioMetals 22: 15-22.
34. Cosio MG, Saetta M & Agusti A (2009) Immunologic aspects of chronic obstructive pulmonary disease. New Engl J Med 360: 2445-2454.
35. Cox AD & Wilkinson SG (1991) Ionizing groups in lipopolysaccharides of Pseudomonas cepacia in relation to antibiotic resistance. Mol Microbiol 5: 641-646.
36. Cramton SE, Gerke C, Schnell NF et al. (1999) The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 67: 5427-5433.
37. Cramton SE, Ulrich M, Götz F & Döring G (2001) Anaerobic conditions induce expression of the polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 69: 4079-4085.
38. Dal Negro R, Micheletto C, Tognella S, Visconti M & Turati C (2008) Tobramycin nebulizer solution in severe COPD patients colonized with Pseudomonas aeruginosa: effects on bronchial inflammation. Adv Ther 25: 1019-1030.
39. D'Argenio DA (2004) The pathogenic lifestyle of Pseudomonas aeruginosa in model systems of virulence. Pseudomonas: Genomics, Life Style and Molecular Architecture, Vol. 1 (Ramos J-L, ed), pp. 477-504. Kluwer Academics/Plenum Publishers, New York.
40. Davies JC (2007) Genotype-phenotype correlations and modifier genes. Cystic Fibrosis (Hodson M, Gededs D & Bush A, eds), pp. 81-86. Hodder Arnold, London.
41. Deretic V, Schurr MJ & Yu H (1995) Pseudomonas aeruginosa, mucoidy and the chronic infection phenotype in cystic fibrosis. Trends Microbiol 3: 351-356.
42. Desai M, Buhler T, Weller PH & Brown MR (1998) Increasing resistance of planktonic and biofilm cultures of Burkholderia cepacia to ciprofloxacin and ceftazidime during exponential growth. J Antimicrob Chemoth 42: 153-160.
43. De Vries SP, Bootsma HJ, Hays JP & Hermans PW (2009) Molecular aspects of Moraxella catarrhalis pathogenesis. Microbiol Mol Biol R 73: 389-406.
44. Di A, Brown ME, Deriy LV et al. (2006) CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 8: 933-944.
45. Di Sant'Agnese PA & Talamo RC (1967) Pathogenesis and physiopathology of cystic fibrosis of the pancreas. New Engl J Med 277: 1287-1294.
46. Dodge JA, Lewis PA, Stanton M & Wilsher J (2007) Cystic fibrosis mortality and survival in the UK: 1947-2003. Eur Respir J 29: 522-526.
47. Döring G (1999) Perspectives of serine proteinase inhibitor therapy for α1-antitrypsin inhibitor deficiency and cystic fibrosis. Pediatr Pulm 28: 363-375.
48. Döring G & Gulbins E (2009) Cystic fibrosis and innate immunity: how chloride channel mutations provoke lung disease. Cell Microbiol 11: 208-216.
49. Döring G & Ratjen F (2005) Cystic fibrosis molecular cell biology. Encyclopedia of Molecular Cell Biology and Molecular Medicine, Vol. 8, 2nd edn (Meyers RA, ed), pp. 623-640. Wiley-VCH, Weinheim.
50. Döring G & Ratjen F (2007) Immunology of cystic fibrosis. Cystic Fibrosis (Hodson M, Gededs D & Bush A, eds), pp. 69-80. Hodder Arnold, London.
51. Döring G, Conway SP, Heijerman HGM et al. (2000) Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16: 749-767.
52. Döring G & Høiby Nthe Consensus Study Group (2004) Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cyst Fibros 3: 67-91.
53. Duan K, Sibley CD, Davidson CJ & Surette MG (2009) Chemical interactions between organisms in microbial communities. Contrib Microbiol 16: 1-17.
54. Eller J, Ede A, Schaberg T, Niederman MS, Mauch H & Lode H (1998) Infective exacerbations of chronic bronchitis. Chest 113: 1542-1548.
55. Engelhardt JF, Yankaskas JR, Ernst SA et al. (1992) Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet 2: 240-248.
56. Ernst RK, Yi EC, Guo L, Lim KB, Burns JL, Hackett M & Miller SI (1999) Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286: 1561-1565.
57. Erwin AL & Smith AL (2007) Nontypeable Haemophilus influenzae: understanding virulence and commensal behavior. Trends Microbiol 15: 355-362.
58. Fagon JY, Chastre J, Trouillet JL, Domart Y, Dombret MC, Bornet M & Gibert C (1990) Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Use of the protected specimen brush technique in 54 mechanically ventilated patients. Am Rev Respir Dis 142: 1004-1008.
59. Ferreira AS, Leitao JH, Silva IN, Pinheiro PF, Sousa SA, Ramos CG & Moreira LM (2010) Distribution of cepacian biosynthesis genes among environmental and clinical Burkholderia strains and role of cepacian exopolysaccharide in resistance to stress conditions. Appl Environ Microb 76: 441-450.
60. Ferrer M, Ioanas M, Arancibia F, Marco MA, De La Bellacasa JP & Torres A (2005) Microbial airway colonization is associated with noninvasive ventilation failure in exacerbation of chronic obstructive pulmonary disease. Crit Care Med 33: 2003-2009.
61. Frederiksen B, Pressler T, Hansen A, Koch C & Hoiby N (2006) Effect of aerosolized rhDNase (pulmozyme) on pulmonary colonization in patients with cystic fibrosis. Acta Paediatr 95: 1070-1074.
62. Gilles-Gonzalez MA & Gonzalez G (2005) Heme-based sensors: defining characteristics, recent developments, and regulatory hypotheses. J Inorg Biochem 99: 1-22.
63. Gilsdorf JR, Marrs CF & Foxman B (2004) Haemophilus influenzae: genetic variability and natural selection to identify virulence factors. Infect Immun 72: 2457-2461.
64. Goerke C & Wolz C (2004) Regulatory and genomic plasticity of Staphylococcus aureus during persistent colonization and infection. Int J Med Microbiol 294: 195-202.
65. Goerke C, Campana S, Bayer MG et al. (2000) Direct quantitative transcript analysis of the agr regulon of Staphylococcus aureus during human infection in comparison to the expression profile in vitro. Infect Immun 68: 1304-1311.
66. Goerke C, Matias y Papenberg S, Dasbach S et al. (2004) Increased frequency of genomic alterations in Staphylococcus aureus during chronic infection is in part due to phage mobilization. J Infect Dis 189: 724-734.
67. Govan JRW, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M, Greening AP & Webb AK (1993) Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 342: 15-19.
68. Green J & Paget MS (2004) Bacterial redox sensors. Nat Rev Microbiol 2: 954-966.
69. Greenberg SB, Allen M, Wilson J & Atmar RL (2000) Respiratory viral infections in adults with and without chronic obstructive pulmonary disease. Am J Resp Crit Care 162: 167-173.
70. Haggie PM & Verkman AS (2007) Cystic fibrosis transmembrane conductance regulator-independent phagosomal acidification in macrophages. J Biol Chem 282: 31422-31428.
71. Haggie PM & Verkman AS (2009) Defective organellar acidification as a cause of cystic fibrosis lung disease - re-examination of a recurring hypothesis. Am J Physiol Lung-C 296: L859-L867.
72. Hancock RE, Mutharia LM, Chan L, Darveau RP, Speert DP & Pier GB (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.
73. Harris JK, De Groote MA, Sagel SD, Zemanick ET, Kapsner R, Penvari C, Kaess H, Deterding RR, Accurso FJ & Pace NR (2007) Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. P Natl Acad Sci USA 104: 20529-20533.
74. Hassett DJ, Sutton MD, Schurr MJ, Herr AB, Caldwell CC & Matu JO (2009) Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways. Trends Microbiol 17: 130-138.
75. Häussler S, Tümmler B, Weissbrodt H, Rohde M & Steinmetz I (1999) Small-colony variants of Pseudomonas aeruginosa in cystic fibrosis. Clin Infect Dis 29: 621-625.
76. Häussler S, Ziegler I, Lottel A, Von Götz F, Rohde M, Wehmhöhner D, Saravanamuthu S, Tümmler B & Steinmetz I (2003) Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. J Med Microbiol 52: 295-301.
77. Herbert S, Worlitzsch D, Dassy B et al. (1997) Regulation of the Staphylococcus aureus capsular polysaccharide type 5: CO2 inhibition in vitro and in vivo. J Infect Dis 176: 431-438.
78. Hill AT, Bayley D & Stockley RA (1999a) The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Resp Crit Care 160: 893-898.
79. Hill AT, Campbell EJ, Bayley DL, Hill SL & Stockley RA (1999b) Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ). Am J Resp Crit Care 160: 1968-1975.
80. Hill AT, Campbell EJ, Hill SL, Bayley DL & Stockley RA (2000) Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med 109: 288-295.
81. Hoboth C, Hoffmann R, Eichner A, Henke C, Schmoldt S, Imhof A, Heesemann J & Hogardt M (2009) Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 200: 118-130.
82. Hoffman LR, Deziel E, D'Argenio DA, Lepine F, Emerson J, McNamara S, Gibson RL, Ramsey BW & Miller SI (2006) Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. P Natl Acad Sci USA 103: 19890-19895.
83. Hoffmann N, Rasmussen TB, Jensen PO, Stub C, Hentzer M, Molin S, Ciofu O, Givskov M, Johansen HK & Hoiby N (2005) Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect Immun 73: 2504-2514.
84. Hogardt M, Roeder M, Schreff AM, Eberl L & Heesemann J (2004) Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS. Microbiology 150: 843-851.
85. Hogardt M, Hoboth C, Schmoldt S, Henke C, Bader L & Heesemann J (2007) Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 195: 70-80.
86. Hogg JC & Timens W (2009) The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4: 435-459.
87. Hogg JC, Chu F, Utokaparch S et al. (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. New Engl J Med 350: 2645-2653.
88. Høiby N & Frederiksen B (2000) Microbiology of cystic fibrosis. Cystic Fibrosis (Hodson ME & Geddes D, eds), pp. 83-108. Arnold, London.
89. Jain M, Ramirez D, Seshadri R, Cullina JF, Powers CA, Schulert GS, Bar-Meir M, Sullivan CL, McColley SA & Hauser AR (2004) Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis. J Clin Microbiol 42: 5229-5237.
90. Jewes LA & Spencer RC (1990) The incidence of anaerobes in the sputum of patients with cystic fibrosis. J Med Microbiol 31: 271-274.
91. Jones AM, Dodd ME & Webb AK (2001) Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas. Eur Respir J 17: 295-301.
92. Joo NS, Lee DJ, Winges KM, Rustagi A & Wine JJ (2004) Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells. J Biol Chem 279: 38854-38860.
93. Keatings VM, Collins PD, Scott DM & Barnes PJ (1996) Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Resp Crit Care 153: 530-534.
94. Keller L & Surette MG (2006) Communication in bacteria: an ecological and evolutionary perspective. Nat Rev Microbiol 4: 249-258.
95. Kerem BT, Rommens JM, Buchanan JA et al. (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245: 1073-1080.
96. Klepac-Ceraj V, Lemon KP, Marti TR et al. (2010) Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa. Environ Microbiol 12: 1293-1303.
97. Klockgether J, Würdemann D, Reva O, Wiehlmann L & Tümmler B (2007) Diversity of the abundant pKLC102/PAGI-2 family of genomic islands in Pseudomonas aeruginosa. J Bacteriol 189: 2443-2459.
98. Kolpen M, Hansen CR, Bjarnsholt T et al. (2010) The respiratory burst of polymorphonuclear leukocytes accelerates oxygen depletion in sputum from CF patients with chronic Pseudomonas aeruginosa lung infection. Thorax 65: 57-62.
99. Kong KF, Vuong C & Otto M (2006) Staphylococcus quorum sensing in biofilm formation and infection. Int J Med Microbiol 296: 133-139.
100. Konstan MW, Hilliard KA, Norvell TM & Berger M (1994) Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Resp Crit Care 150: 448-454.
101. Kummerli R, Griffin AS, West SA, Buckling A & Harrison F (2009) Viscous medium promotes cooperation in the pathogenic bacterium Pseudomonas aeruginosa. P Roy Soc Lond B 276: 3531-3538.
102. Lee DG, Urbach JM, Wu G et al. (2006) Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol 7: R90.
103. Lee VT, Smith RS, Tummler B & Lory S (2005) Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection. Infect Immun 73: 1695-1705.
104. Lehrer RI & Ganz T (2002) Defensins of vertebrate animals. Curr Opin Immunol 14: 96-102.
105. Lopez AD, Shibuya K, Rao C et al. (2006) Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J 27: 397-412.
106. Lory S, Merighi M & Hyodo M (2009) Multiple activities of c-di-GMP in Pseudomonas aeruginosa. Nucleic Acids Symp Ser 53: 51-52.
107. Luzar MA, Thomassen MJ & Montie TC (1985) Flagella and motility alterations in Pseudomonas aeruginosa strains from patients with cystic fibrosis: relationship to patient clinical condition. Infect Immun 50: 577-582.
108. Mahenthiralingam E, Campbell ME & Speert DP (1994) Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect Immun 62: 596-605.
109. Mahenthiralingam E, Urban TA & Goldberg JB (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3: 144-156.
110. Maiden MC (2006) Multilocus sequence typing of bacteria. Annu Rev Microbiol 60: 561-588.
111. Mandsberg LF, Ciofu O, Kirkby N, Christiansen LE, Poulsen HE & Høiby N (2009) Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob Agents Ch 53: 2483-2491.
112. Martinez-Solano L, Macia MD, Fajardo A, Oliver A & Martinez JL (2008) Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clin Infect Dis 47: 1526-1533.
113. Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW & Boucher RC (1998) Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95: 1005-1010.
114. Matsui H, Verghese MW, Kesimer M et al. (2005) Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfaces. J Immunol 175: 1090-1099.
115. McKenney D, Pouliot KL, Wang Y et al. (1999) Broadly protective vaccine for Staphylococcus aureus based on an in vivo-expressed antigen. Science 284: 1523-1527.
116. Miravitlles M, Espinosa C, Fernandez-Laso E, Martos JA, Maldonado JA & Gallego MStudy Group of Bacterial Infection in COPD (1999) Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 116: 40-46.
117. Mitchell G, Brouillette E, Lalonde Séguin D, Asselin A-E, Lebeau Jacob C & Malouin F (2010) A role for sigma factor B in the emergence of Staphylococcus aureus small-colony variants and elevated biofilm production resulting from an exposure to aminoglycosides. Microbial Pathogenesis 48: 18-27.
118. Monso E, Ruiz J, Rosell A, Manterola J, Fiz J, Morera J & Ausina V (1995) Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Resp Crit Care 152: 1316-1320.
119. Montanari S, Oliver A, Salerno P, Mena A, Cariani L, Bretoni G, Conese M, Tümmler B, Döring G & Bragonzi A (2007) Biological cost of hypermutation in Pseudomonas aeruginosa strains from patients with cystic fibrosis. Microbiology 153: 1445-1454.
120. Murphy TF & Parameswaran G (2009) Moraxella catarrhalis, a human respiratory tract pathogen. Clin Infect Dis 49: 124-131.
121. Murphy TF, Brauer AL, Schiffmacher AT & Sethi S (2004) Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Resp Crit Care 170: 266-272.
122. Murphy TF, Brauer AL, Grant BJ & Sethi S (2005) Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response. Am J Resp Crit Care 172: 195-199.
123. Murphy TF, Brauer AL, Eschberger K, Lobbins P, Grove L, Cai X & Sethi S (2008) Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Resp Crit Care 177: 853-860.
124. Nguyen D & Singh PK (2006) Evolving stealth: genetic adaptation of Pseudomonas aeruginosa during cystic fibrosis infections. P Natl Acad Sci USA 103: 8305-8306.
125. Nocker A, Burr M & Camper AK (2007) Genotypic microbial community profiling: a critical technical review. Microb Ecol 54: 276-289.
126. Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48: 1429-1449.
127. Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B & Moghazeh S (1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12: 3967-3975.
128. Novick RP, Projan SJ, Kornblum J et al. (1995) The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol Gen Genet 248: 446-458.
129. Nseir S, Di Pompeo C, Cavestri B et al. (2006) Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: prevalence, risk factors, and outcome. Crit Care Med 34: 2959-2966.
130. Oliver A, Cantón R, Campo P, Baquero F & Blázquez J (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288: 1251-1254.
131. Oliver A, Baquero F & Blazquez J (2002) The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonasaeruginosa: molecular characterization of naturally occurring mutants. Mol Microbiol 43: 1641-1650.
132. Pamp SJ, Gjermansen M, Johansen HK & Tolker-Nielsen T (2008) Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 68: 223-240.
133. Parameswaran G, Wrona C, Murphy T & Sethi S (2009) Moraxella catarrhalis acquisition, airway inflammation and protease-antiprotease balance in chronic obstructive pulmonary disease. BMC Infect Dis 9: 178.
134. Perez Vidakovics ML & Riesbeck K (2009) Virulence mechanisms of Moraxella in the pathogenesis of infection. Curr Opin Infect Dis 22: 279-285.
135. Pier GB (2000) Role of the CF transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. P Natl Acad Sci USA 97: 8822-8828.
136. Pollock JD, Williams DA, Gifford MAC et al. (1995) Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet 9: 202-209.
137. Prunier AL, Malbruny B, Laurans M, Brouard J, Duhamel JF & Leclercq R (2003) High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. J Infect Dis 187: 1709-1716.
138. Quon BS, Gan WQ & Sin DD (2008) Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest 133: 756-766.
139. Rahman I & MacNee W (1996) Oxidant/antioxidant imbalance in smokers and chronic obstructive pulmonary disease. Thorax 51: 348-350.
140. Rakhimova E, Wiehlmann L, Brauer AL, Sethi S, Murphy TF & Tummler B (2009) Pseudomonas aeruginosa population biology in chronic obstructive pulmonary disease. J Infect Dis 200: 1928-1935.
141. Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J & Barnes NC (2006) Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Db Syst Rev 2: CD004403.
142. Ramsey DM & Wozniak DJ (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.
143. Ratjen F, Hartog CM, Paul K, Wermelt J & Braun J (2002) Matrix metalloproteases in BAL fluid of cystic fibrosis patients and their modulation by treatment with dornase alpha. Thorax 57: 930-934.
144. Rau MH, Hansen SK, Johansen HK, Thomsen LE, Workman CT, Nielsen KF, Jelsbak L, Høiby N, Yang L & Molin S (2010) Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts. Environ Microbiol April 7. Epub ahead of print.
145. Riedel K, Hentzer M, Geisenberger O, Huber B, Steidle A, Wu H, Høiby N, Givskov M, Molin S & Eberl L (2001) N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology 147: 3249-3262.
146. Riethmüller J, Anthonysamy J, Serra E, Schwab M, Döring G & Gulbins E (2009) Therapeutic efficacy and safety of amitriptyline in patients with cystic fibrosis. Cell Physiol Biochem 24: 65-72.
147. Riordan JR, Rommens JM, Kerem BS et al. (1989) Identification of the Cystic Fibrosis Gene: Cloning and characterization of complementary DNA. Science 245: 1066-1073.
148. Roede BM, Bresser P, Prins JM, Schellevis F, Verheij TJ & Bindels PJ (2009) Reduced risk of next exacerbation and mortality associated with antibiotic use in COPD. Eur Respir J 33: 282-288.
149. Rogers GB, Hart CA, Mason JR et al. (2003) Bacterial diversity in cases of lung infection in cystic fibrosis patients: 16S ribosomal DNA (rDNA) length heterogeneity PCR and 16S rDNA terminal reobligation fragment length polymorphism profiling. J Clin Microbiol 41: 3548-3558.
150. Rogers GB, Carroll MP, Serisier DJ et al. (2004) Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16S ribosomal DNA terminal reobligation fragment length polymorphism profiling. J Clin Microbiol 42: 5176-5183.
151. Rogers GB, Carroll MP, Serisier DJ et al. (2006) Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis. J Clin Microbiol 44: 2601-2604.
152. Rogers GB, Carroll MP & Bruce KD (2009) Studying bacterial infections through culture-independent approaches. J Med Microbiol 58: 1401-1418.
153. Roman F, Canton R, Perez-Vazquez M, Baquero F & Campos J (2004) Dynamics of long-term colonization of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains. J Clin Microbiol 42: 1450-1459.
154. Rommens JM, Iannuzzi MC, Kerem BS et al. (1989) Identification of the Cystic Fibrosis Gene: Chromosome walking and jumping. Science 245: 1059-1065.
155. Rosell A, Monso E, Soler N et al. (2005) Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch Intern Med 165: 891-897.
156. Sabra W, Lunsdorf H & Zeng AP (2003) Alterations in the formation of lipopolysaccharide and membrane vesicles on the surface of Pseudomonas aeruginosa PAO1 under oxygen stress conditions. Microbiology 149: 2789-2795.
157. Sadowska B, Bonar A, Von Eiff C et al. (2002) Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants. FEMS Immunol Med Mic 32: 191-197.
158. Sahly H, Schubert S, Harder J, Rautenberg P, Ullmann U, Schroder H & Podschun R (2003) Burkholderia is highly resistant to human beta-defensin 3. Antimicrob Agents Ch 47: 1739-1741.
159. Salunkhe P, Smart CH, Morgan JA, Panagea S, Walshaw MJ, Hart CA, Geffers R, Tümmler B & Winstanley C (2005a) A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol 187: 4908-4920.
160. Salunkhe P, Töpfer T, Buer J & Tümmler B (2005b) Genome-wide transcriptional profiling of the steady-state response of Pseudomonas aeruginosa to hydrogen peroxide. J Bacteriol 187: 2565-2572.
161. Schneider M, Muhlemann K, Droz S, Couzinet S, Casaulta C & Zimmerli S (2008) Clinical characteristics associated with isolation of small-colony variants of Staphylococcus aureus and Pseudomonas aeruginosa from respiratory secretions of patients with cystic fibrosis. J Clin Microbiol 46: 1832-1834.
162. Schweda EK, Richards JC, Hood DW & Moxon ER (2007) Expression and structural diversity of the lipopolysaccharide of Haemophilus influenzae: implication in virulence. Int J Med Microbiol 297: 297-306.
163. Seemungal T, Harper-Owen R, Bhowmik A et al. (2001) Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Resp Crit Care 164: 1618-1623.
164. Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ & Wedzicha JA (2008) Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Resp Crit Care 178: 1139-1147.
165. Segal BH, Ding L & Holland SM (2003) Phagocyte NADPH oxidase, but not inducible nitric oxide synthase, is essential for early control of Burkholderia cepacia and Chromobacterium violaceum infection in mice. Infect Immun 71: 205-210.
166. Selsted ME & Quellette AJ (2003) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6: 551-557.
167. Sethi S & Murphy TF (2001) Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 14: 336-363.
168. Sethi S & Murphy TF (2008) Infection in the pathogenesis and course of chronic obstructive pulmonary disease. New Engl J Med 359: 2355-2365.
169. Sethi S, Evans N, Grant BJ & Murphy TF (2002) New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. New Engl J Med 347: 465-471.
170. Sethi S, Wrona C, Eschberger K, Lobbins P, Cai X & Murphy TF (2008) Inflammatory profile of new bacterial strain exacerbations of chronic obstructive pulmonary disease. Am J Resp Crit Care 177: 491-497.
171. Sibley CD, Parkins MD, Rabin HR, Duan K, Norgaard JC & Surette MG (2008) A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. P Natl Acad Sci USA 105: 15070-15075.
172. Sibley CD, Parkins MD, Rabin HR & Surette MG (2009) The relevance of the polymicrobial nature of airway infection in the acute and chronic management of patients with cystic fibrosis. Curr Opin Investig D 10: 787-794.
173. Silo-Suh L, Suh SJ, Phibbs PV & Ohman DE (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.
174. Silverman EK, Spira A & Pare PD (2009) Genetics and genomics of chronic obstructive pulmonary disease. Proc Am Thorac Soc 6: 539-542.
175. Slevogt H, Zabel S, Opitz B et al. (2008) CEACAM1 inhibits toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells. Nat Immunol 9: 1270-1278.
176. Smith EE, Buckley DG, Wu Z et al. (2006) Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. P Natl Acad Sci USA 103: 8487-8492.
177. Smolonska J, Wijmenga C, Postma DS & Boezen HM (2009) Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years' research. Am J Resp Crit Care 180: 618-631.
178. Soler N, Torres A, Ewig S et al. (1998) Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Resp Crit Care 157: 1498-1505.
179. Soler N, Ewig S, Torres A, Filella X, Gonzalez J & Zaubet A (1999) Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur Respir J 14: 1015-1022.
180. Soler N, Agusti C, Angrill J, Puig De la Bellacasa J & Torres A (2007) Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease. Thorax 62: 29-35.
181. phox-/- mice. Cell Microbiol 9: 2817-2825.
182. Speert DP, Bond M, Woodman RC & Curnutte JT (1994) Infection with Pseudomonas cepacia in chronic granulomatous disease: role of nonoxidative killing by neutrophils in host defense. J Infect Dis 170: 1524-1531.
183. Srikhanta YN, Fox KL & Jennings MP (2010) The phasevarion: phase variation of type III DNA methyltransferases controls coordinated switching in multiple genes. Nat Rev Microbiol 8: 196-206.
184. Starkey M, Hickman JA, Ma L et al. (2009) Pseudomonas aeruginosa Rugose Small-Colony Variants Have Adaptations That Likely Promote Persistence in the Cystic Fibrosis Lung. J Bacteriol 191: 3492-3503.
185. Starner TD, Zhang N, Kim GH, Apicella MA & McCray PB Jr (2006) Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Resp Crit Care 174: 213-220.
186. Stockley RA (1999) Neutrophils and protease/antiprotease imbalance. Am J Resp Crit Care 160: S49-S52.
187. Stover CK, Pham XQ, Erwin AL et al. (2000) Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406: 959-964.
188. Suh SJ, Silo-Suh L, Woods DE, Hassett DJ, West SE & Ohman DE (1999) Effect of rpoS mutation on the stress response and expression of virulence factors in Pseudomonas aeruginosa. J Bacteriol 181: 3890-3897.
189. Taddei F, Radman M, Maynard-Smith J, Toupance B, Gouyon PH & Godelle B (1997) Role of mutator alleles in adaptive evolution. Nature 387: 700-702.
190. Taylor RF, Hodson ME & Pitt TL (1993) Adult cystic fibrosis: association of acute pulmonary exacerbations and increasing severity of lung disease with auxotrophic mutants of Pseudomonas aeruginosa. Thorax 48: 1002-1005.
191. Teichgräber V, Ulrich M, Riethmüller J et al. (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in CF. Nat Med 14: 382-391.
192. Thomas SR, Ray A, Hodson ME & Pitt TL (2000) Increased sputum amino acid concentrations and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease. Thorax 55: 795-797.
193. Thomassen MJ, Demko CA, Boxerbaum B, Stern RC & Kuchenbrod PJ (1979) Multiple of isolates of Pseudomonas aeruginosa with differing antimicrobial susceptibility patterns from patients with cystic fibrosis. J Infect Dis 140: 873-880.
194. Tosi MF, Zakem H & Berger M (1990) Neutrophil elastase cleaves C3bi on opsonized Pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest 86: 300-308.
195. Tümmler B (2006) Clonal variations in Pseudomonas aeruginosa. Pseudomonas: Molecular Biology of Emerging Issues (Ramos JL & Levesque R, eds), pp. 35-68. Springer, Heidelberg.
196. Tunney MM, Field TR, Moriarty TF et al. (2008) Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Resp Crit Care 177: 995-1001.
197. Ulrich M, Herbert S, Berger J, Bellon G, Louis D, Münker G & Döring G (1998) Localization of Staphylococcus aureus in infected airways of patients with CF and in a cell culture model of S. aureus adherence. Am J Resp Crit Care 19: 83-91.
198. Ulrich M, Bastian M, Cramton SE et al. (2007) The staphylococcal respiratory response regulator SrrAB induces ica gene transcription and PIA expression, protecting Staphylococcus aureus from neutrophil killing under anaerobic growth conditions. Mol Microbiol 65: 1276-1287.
199. Ulrich M, Worlitzsch D, Viglio S et al. (2010) Alveolar inflammation in cystic fibrosis. J Cyst Fibros 9: 217-227.
200. Van Delden C (2004) Virulence factors of Pseudomonas aeruginosa. Pseudomonas: Virulence and Gene Regulation, Vol. 2 (Ramos J-L, ed), pp. 3-46. Kluwer Academics/Plenum Publishers, New York.
201. Verkman AS, Song Y & Thiagarajah JR (2003) Role of airway surface liquid and submucosal glands in CF lung disease. Am J Physiol-Cell Ph 284: C2-C15.
202. Vinion-Dubiel AD & Goldberg JB (2003) Lipopolysaccharide of Burkholderia cepacia complex. J Endotoxin Res 9: 201-213.
203. Von Eiff C (2008) Staphylococcus aureus small colony variants: a challenge to microbiologists and clinicians. Int J Antimicrob Agents 31: 507-510.
204. Watson ME Jr, Burns JL & Smith AL (2004) Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum. Microbiology 150: 2947-2958.
205. Wehmhöner D, Häussler S, Tümmler B, Jänsch L, Bredenbruch F, Wehland J & Steinmetz I (2003) Inter- and intraclonal diversity of the Pseudomonas aeruginosa proteome manifests within the secretome. J Bacteriol 185: 5807-5814.
206. Whitchurch CB, Tolker-Nielsen T, Ragas PC & Mattick JS (2002) Extracellular DNA required for bacterial biofilm formation. Science 295: 1487.
207. White AJ, Gompertz S, Bayley DL, Hill SL, O'Brien C, Unsal I & Stockley RA (2003) Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis. Thorax 58: 680-685.
208. Wiehlmann L, Wagner G, Cramer N et al. (2007) Population structure of Pseudomonas aeruginosa. P Natl Acad Sci USA 104: 8101-8106.
209. Williams P & Camara M (2009) Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 12: 182-191.
210. Wimpenny J, Manz W & Szewzyk U (2000) Heterogeneity in biofilms. FEMS Microbiol Rev 24: 661-671.
211. Winstanley C & Fothergill JL (2009) The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections. FEMS Microbiol Lett 290: 1-9.
212. Wood AM & Stockley RA (2006) The genetics of chronic obstructive pulmonary disease. Respir Res 7: 130.
213. Woods DE, Schaffer MS, Rabin HR, Campbell GD & Sokol PA (1986) Phenotypic comparison of Pseudomonas aeruginosa strains isolated from a variety of clinical sites. J Clin Microbiol 24: 260-264.
214. Worlitzsch D, Tarran R, Ulrich M et al. (2002) Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 109: 317-325.
215. Worlitzsch D, Rintelen C, Böhm K et al. (2009) Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. Clin Microbiol Infec 15: 454-460.
216. Xu KD, Stewart PS, Xia F, Huang CT & McFeters GA (1998) Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is determined by oxygen availability. Appl Environ Microb 64: 4035-4039.