Pseudomonas aeruginosa biofilms in cystic fibrosis

Future Microbiology

Volumn 5, Issue 11, 2010, Pages 1663-1674

  Høiby, Niels ^a   Ciofu, Oana ^b   Bjarnsholt, Thomas ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

antibiotic tolerance; biofilm; chronic infection; cystic fibrosis; Pseudomonas aeruginosa

Indexed keywords

ALGINIC ACID; CIPROFLOXACIN; TOBRAMYCIN;

ADAPTATION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ANTIBODY RESPONSE; BACTERIAL GROWTH; BACTERIAL SURVIVAL; BIOFILM; CYSTIC FIBROSIS; HUMAN; IMMUNE COMPLEX DISEASE; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MUTATION; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; REVIEW; TISSUE INJURY;

ANTI-BACTERIAL AGENTS; BIOFILMS; BIOPOLYMERS; CHRONIC DISEASE; CYSTIC FIBROSIS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; HUMANS; INFLAMMATION; LUNG; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS; VIRULENCE FACTORS;

BACTERIA (MICROORGANISMS); PSEUDOMONAS AERUGINOSA;

EID: 78650181025     PISSN: 17460913     EISSN: None     Source Type: Journal    
DOI: 10.2217/fmb.10.125     Document Type: Review

References (115)

1. Boucher RC. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur. Resp. J. 23(1), 146-158 (2007).
2. Høiby N, Johansen HK, Moser C, Song ZJ, Ciofu O, Kharazmi A: Pseudomonas aeruginosa and the bioflm mode of growth. Microbes Infect. 3, 1-13 (2001).
3. Armstrong DS, Grimwood K, Carzino R, Carlin JB, Olinsky A, Phelan PD: Lower respiratory infection and infammation in infants with newly diagnosed cystic fibrosis. BMJ 310(6994), 1571-1572 (1995).
4. Armstrong DS, Hook SM, Jamsen KM et al.: Lower airway infammation in infants with cystic fibrosis detected by newborn screening. Ped. Pulmonol. 40, 500-510 (2005).
5. Frederiksen B, Koch C, Høiby N: The changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients, 1974-1995. Ped. Pulmonol. 28, 159-166 (1999).
6. Hoffmann N, Rasmussen TB, Jensen PØ et al.: Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect. Immun. 73, 2504-2514 (2005).
7. Høiby N: P. aeruginosa in cystic fibrosis patients resists host defenses, antibiotics. Microbe (ASM) 1(12), 571-577 (2006).
8. Jelsbak L, Johansen HK, Frost A-L et al.: Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients. Infect. Immun. 75, 2214-2224 (2007).
9. Bjarnsholt T, Jensen PØ, Fiandaca MJ et al.: Pseudomonas aeruginosa bioflms in the respiratory tract of cystic fibrosis patients. Ped. Pulmonol. 44, 547-558 (2009).
10. Armstrong DS, Grimwood K, Carlin JB et al.: Lower airway infammation in infants and young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 156(4), 1197-1204 (1997).
11. Kolpen M, Hansen CR, Bjarnsholt T et al.: Polymorphonuclear leukocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis. Thorax 65, 57-62 (2010).
12. Miller RA, Britigan BE: Role of oxidants in microbial pathophysiology. Clin. Microbiol. Rev. 10, 1-18 (1997).
13. Egestein A, Schmidt A, Herwald H: Trends in Innate Immunity. Schmidt A, Herwald H (Eds). Karger, Basel, Switzerland (2008).
14. Hull J, Vervaart P, Grimwood K, Phelan P: Pulmonary oxidative stress response in young children with cystic fibrosis. Thorax 52(6), 557-560 (1997). (Pubitemid 27298509)
15. Mathee K, Ciofu O, Sternberg C et al.: Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung. Microbiology 145, 1349-1357 (1999).
16. Ciofu O, Johanneson M, Hermansen NO, Meyer P, Høiby N: Investigation of the algT operon sequence in mucoid and non-mucoid P. aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro revertants. Microbiology 154, 103-113 (2008).
17. Ciofu O, Mandsberg LF, Bjarnsholt T, Wassermann T, Høiby N: Genetic adaptation of P. aeruginosa during chronic lung infection of patients with cystic fibrosis: strong and weak mutators with heterogenous genetic backgrounds emerge in mucA and/or lasR mutants. Microbiology 156, 1108-1119 (2010).
18. Boucher JC, Martinezsalazar J, Schurr MJ, Mudd MH, Yu H, Deretic V: Two distinct loci affecting conversion to mucoidy in Pseudomonas aeruginosa in cystic fibrosis encode homologs of the serine protease HtrA: J. Bacteriol. 178(2), 511-523 (1996).
19. Bragonzi A, Wiehlmann L, Klockgether J et al.: Sequence diversity of the mucoid mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 152, 3261-3269 (2006).
20. Song ZJ, Wu H, Ciofu O et al.: Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection. J. Med. Microbiol. 52(9), 731-740 (2003).
21. Ciofu O, Riis B, Pressler T, Poulsen HE, Høiby N: Occurrence of hypermutable P. aeruginosa in cystic fibrosis patients is associates with the oxidative stress caused by chronic lung infammation. Antimicrob. Agents Chemother. 49, 2276-2282 (2005).
22. Bjarnsholt T, Jensen PØ, Rasmussen TB et al.: Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 151, 3873-3880 (2005).
23. Bjarnsholt T, Jensen P-Ø, Burmølle M et al.: Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151, 373-383 (2005).
24. Jensen PØ, Bjarnsholt T, Phipps R et al.: Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 153, 1329-1338 (2007).
25. Hoffmann N, Lee B, Hentzer M et al.: Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary gowth phase killing of P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr-/- mice. Antimicrob. Agents Chemother. 51, 3677-3687 (2007).
26. Westh JB: Pulmonary Physiology and Pathophysiology. Lippincott Williams & Wilkins, PA, USA (2001).
27. Levy J, Smith AL, Koup JR, Williams-Warren J, Ramsey B: Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study. J. Pediat. 105, 117-124 (1984).
28. Ramsey BW, Pepe MS, Quan JM et al.: Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N. Engl. J. Med. 340(1), 23-30 (1999).
29. Le Brun PPH: Optimization of Antibiotic Inhalation Therapy in Cystic Fibrosis. Studies on Nebulized Tobramycin. Development of a Colistin Dry Powder Inhaler System. University of Groningen, Groningen, Holland (2001).
30. Gibson RL, Emerson J, McNamara S et al.: Signifcant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 167(6), 841-849 (2003).
31. Geller DE, Pitlick WH, Nardella PA, Tracewell WG, Ramsey BW: Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 122(1), 219-226 (2002).
32. Ratjen F, Rietschel E, Kasel D et al.: Pharmacokinetics of inhaled colistin in patients with cystic fibrosis. J. Antimicrob. Chemother. 57, 306-311 (2006). (Pubitemid 43160174)
33. Permin H, Koch C, Høiby N, Christensen HO, Møller AF, Møller S: Ceftazidime treatment of chronic Pseudomonas aeruginosa respiratory tract infection in cystic fibrosis. J. Antimicrob. Chemother. 12(Suppl. A), 313-323 (1983). (Pubitemid 13001005)
34. Pamp SJ, Gjermansen M, Johansen HK, Tolker-Nielsen T: Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa bioflms is linked to metabolically active cells, and depends on the prm and mexAB-oprM genes. Mol. Microbiol. 68, 223-240 (2008).
35. Jensen T, Pedersen SS, Garne S, Heilmann C, Høiby N, Koch C: Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J. Antimicrob. Chemother. 19, 831-838 (1987). (Pubitemid 17092071)
36. Valerius NH, Koch C, Høiby N: Prevention of chronic Pseudomonas-aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 338(8769), 725-726 (1991).
37. Cedergren J, Follin P, Forslund T, Lindmark M, Sundquist T, Skogh T: Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils. APMIS 111, 963-968 (2003).
38. Hassett DJ, Cuppoletti J, Trapnell B et al.: Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa bioflms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Advan. Drug Delivery Rev. 54(11), 1425-1443 (2002).
39. Pedersen SS, Kharazmi A, Espersen F, Høiby N: Pseudomonas- aeruginosa alginate in cystic fibrosis sputum and the infammatory response. Infect. Immun. 58(10), 3363-3368 (1990).
40. Pedersen SS, Espersen F, Høiby N, Jensen T: Immunoglobulin A and immunoglobulin G antibody responses to alginates from Pseudomonas aeruginosa in cystic fibrosis. J. Clin. Microbiol. 28, 747-755 (1990). (Pubitemid 20123830)
41. Pedersen SS, Møller H, Espersen F, Sørensen CH, Jensen T, Høiby N: Mucosal immunity to Pseudomonas-aeruginosa alginate in cystic fibrosis. APMIS 100(4), 326-334 (1992).
42. Craig A, Mai J, Cai S, Jeyaseelan S: Neutrophil recruitement to the lungs during bacterial pneumonia. Infect. Immun. 77, 568-575 (2009).
43. Goldstein W, Döring G: Lysosomal enzymes from polymorphonuclear leukocytes and proteinase inhibitors in patients with cystic fibrosis. Am. Rev. Respir. Dis. 134, 49-56 (1986).
44. Bruce MC, Poncz L, Klinger JD, Stern RC, Tomashefski JF, Dearborn DG: Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis. Am. Rev. Respir. Dis. 132, 529-535 (1985).
45. Ammitzbøll T, Pedersen SS, Espersen F, Schiøler H: Excretion of urinary collagen metabolites correlates to severity of pulmonary disease in cystic fibrosis. Acta Paediatr. Scand. 77, 842-846 (1988).
46. Johansen HK: Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: experimental studies in animals. APMIS 104(Suppl. 63), 5-42 (1996).
47. Moser C, Kjærgaard S, Pressler T, Kharazmi A, Koch C, Høiby N: The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type. APMIS 108, 329-335 (2000).
48. Tiddens HAWM: Detecting early structural lung damage in cystic fibrosis. Ped. Pulmonol. 34, 228-231 (2002).
49. Jensen PØ, Bjarnsholt T, Phipps R et al.: Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 153, 1329-1338 (2007).
50. Worlitzsch D, Tarran R, Ulrich M et al.: Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Invest. 109(3), 317-325 (2002).
51. Høiby N: Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic signifcance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis. A survey. Acta Pathol. Microbiol. Scand. Suppl. 262(Suppl. C), 3-96 (1977).
52. Haussler S, Tummler B, Weissbrodt H, Rohde M, Steinmetz I: Small-colony variants of Pseudomonas aeruginosa in cystic fibrosis. Clin. Infect. Dis. 29(3), 621-625 (1999).
53. Haussler S: Bioflm formation by the small colony variant phenotype of Pseudomonas aeruginosa. Environ. Microbiol. 6(6), 546-551 (2004).
54. Rainey PB, Travisano M: Adaptive radiation in a heterogenous environment. Nature 394, 69-72 (1998).
55. Wyckoff TJO, Thomas B, Hassett DJ, Wozniak DJ: Static growth of mucoid Pseudomonas aeruginosa selects for non-mucoid variants that have acquired fagellum-dependent motility. Microbiology 148, 3423-3430 (2002).
56. Spiers AJ, Buckling A, Rainey PB: The causes of Pseudomonas diversity. Microbiology 146, 2345-2350 (2000).
57. Yang L, Haagensen JAJ, Jelsbak L et al.: In situ growth rates and bioflm development of Pseudomonas aeruginosa populations in chronic lung infection. J. Bacteriol. 190, 2767-2776 (2008).
58. Lee B, Haagensen JAJ, Ciofu O, Andersen JB, Høiby N, Molin S: Heterogeneity of bioflms formed by non-mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. J. Clin. Microbiol. 43, 5247-5255 (2005).
59. Pedersen SS, Høiby N, Espersen F, Koch C: Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. Thorax 47, 6-13 (1992).
60. Moser C, van Gennip M, Bjarnsholt T et al.: Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 117, 95-107 (2009).
61. Lee B, Schjerling CK, Kirkby N et al.: Mucoid Pseudomonas aeruginosa maintain the in vitro bioflm formation capacity and show a conserved gene expression profle compared to the paired non-mucoid isolates during the chronic lung infection of patients with cystic fibrosis. Clin. Microbiol. Infect. (2010) (In press).
62. Matsui H, Verghese MW, Kesimer M et al.: Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on epithelial surfaces. J. Immunol. 175, 1090-1099 (2005).
63. Shah PL, Scott SF, Fuchs HJ, Geddes DM, Hodson ME: Medium term treatment of stable stage cystic fibrosis with recombinant human DNase I. Thorax 50(4), 333-338 (1995).
64. Brandt T, Breitenstein S, Vonderhardt H, Tummler B: DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase. Thorax 50(8), 880-882 (1995).
65. Ratjen F, Tummler B: Comparison of the in vitro and in vivo response to inhaled DNase in patients with cystic fibrosis. Thorax.54(1), 91 (1999).
66. Szaff M, Høiby N, Flensborg EW: Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediat. Scand. 72, 651-657 (1983). (Pubitemid 13048784)
67. Anwar H, Strap JL, Chen K, Costerton JW: Dynamic interactions of bioflms of mucoid Pseudomonas-aeruginosa with tobramycin and piperacillin. Antimicrob. Agents Chemother. 36(6), 1208-1214 (1992).
68. Anwar H, Strap JL, Costerton JW: Establishment of aging bioflms: possible mechanism of bacterial resistance to antimicrobial therapy. Antimicrob. Agents Chemother. 36, 1347-1351 (1992).
69. Smith AL, Fiel SB, MayerHamblett N, Ramsey B, Burns JL: Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration - lack of association in cystic fibrosis. Chest 123(5), 1495-1502 (2003).
70. Borriello G, Werner E, Roe F, Kim AM, Ehrlich GD, Stewart PS: Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in bioflms. Antimicrob. Agents Chemother. 48(7), 2659-2664 (2004).
71. Keren I, Kaldalu N, Spoering A, Wang YP, Lewis K: Persister cells and tolerance to antimicrobials. FEMS Microbiol. Lett. 230(1), 13-18 (2004).
72. Moskowitz SM, Foster JM, Emerson J, Burns JL: Clinically feasible bioflm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J. Clin. Microbiol. 42(5), 1915-1922 (2004).
73. Haagensen J, Klausen M, Ernst RK et al.: Differentiation and distribution of colistin-and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa bioflms. J. Bacteriol. 189, 28-37 (2007).
74. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O: Antibiotic resistance of bacterial bioflms. Int. J. Antimicrob. Agents 35, 322-332 (2010).
75. Ciofu O, Fussing V, Bagge N, Koch C, Høiby N: Characterization of paired mucoid/ non-mucoid Pseudomonas aeruginosa isolates from Danish cystic fibrosis patients: antibiotic resistance, beta-l acta mas e activity and RiboPrinting. J. Antimicrob. Chemother. 48(3), 391-396 (2001).
76. Giwercman B, Lambert PA, Rosdahl VT, Shand GH, Høiby N: Rapid emergence of resistance in Pseudomonas-aeruginosa in cystic fibrosis patients due to in vivo selection of stable partially derepressed p-lactamase producing strains. J. Antimicrob. Chemother. 26(2), 247-259 (1990).
77. Giwercman B, Meyer C, Lambert PA, Reinert C, Høiby N: High-level p-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. Antimicrob. Agents Chemother. 36(1), 71-76 (1992).
78. Dibdin GH, Assinder SJ, Nichols WW, Lambert PA: Mathematical model of p-lactam penetration into a bioflm of Pseudomonas aeruginosa while undergoing simultaneous inactivation by released p-lactamases. J. Antimicrob. Chemother. 38(5), 757-769 (1996).
79. Denton M, Littlewood JM, Brownlee KG, Conway SP, Todd NJ: Spread of p-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis unit. Lancet 348(9041), 1596-1597 (1996).
80. Bagge N, Ciofu O, Hentzer M, Campbell JIA, Givskov M, Høiby N: Constitutive high expression of chromosomal p-lactamase in Pseudomonas aeruginosa caused by a new insertion sequence (IS1669) located in ampD: Antimicrob. Agents Chemother. 46(11), 3406-3411 (2002).
81. Jalal S, Ciofu O, Høiby N, Gotoh N, Wretlind B: Molecular mechanisms of fuoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob. Agents Chemother. 44(5), 710-712 (2000).
82. Saiman L, Mehar F, Niu WW et al.: Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation. Clin. Infect. Dis. 23(3), 532-537 (1996).
83. Westbrock B, Wadman S, Sherman DR et al.: Characterization of a Pseudomonas aeruginosa effux pump contributing to aminoglycoside impermeability. Antimicrob. Agents Chemother. 43(12), 2975-2983 (1999).
84. Burns JL, VanDalfsen JM, Shawar RM et al.: Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial fora in patients with cystic fibrosis. J. Infect. Dis. 179(5), 1190-1196 (1999).
85. MacLeod DL, Nelson LE, Shawar RM et al.: Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycin treatment. J. Infect. Dis. 181(3), 1180-1184 (2000).
86. Islam S, Oh H, Jalal S, Ciofu O, Høiby N, Wretlind B: Chromosomal resistance mechanisms fo aminoglycosides in Pseudomonas aeruginosa cystic fibrosis isolates. Clin. Microbiol. Infect. 15, 60-66 (2009).
87. Denton M, Kerr K, Mooney L et al.: Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center. Pediatr. Pulmonol. 34, 257-261 (2002).
88. Moskowitz SM, Ernst RK, Miller SI: 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(2), 575-579 (2004).
89. Johansen HK, Moskowitz SM, Ciofu O, Pressler T, Høiby N: Spread of colistin-resistant non-mucoid Pseudomonas aeruginosa among chronically infected Danish cystic fibrosis patients. J. Cystic Fibrosis 7, 391-397 (2008).
90. Bagge N, Ciofu O, Skovgaard LT, Høiby N: Rapid development in vitro and in vivo of resistance to ceftazidime in bioflm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase. APMIS 108(9), 589-600 (2000).
91. Bagge N, Hentzer M, Andersen JB, Ciofu O, Givskov M, Høiby N: Dynamics and spatial distribution of p-lactamase expression in Pseudomonas aeruginosa bioflms. Antimicrob. Agents Chemother. 48(4), 1168-1174 (2004).
92. Bagge N, Schuster M, Hentzer M et al.: Pseudomonas aeruginosa bioflms exposed to imipenem exhibit changes in global gene expression and p-lactamase and alginate production. Antimicrob. Agents Chemother. 48(4), 1175-1187 (2004).
93. Oliver A, Canton R, Campo P, Baquero F, Blazquez J: High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288(5469), 1251-1253 (2000).
94. Mandsberg LF, Ciofu O, Kirkby N, Christiansen LE, Poulsen HE, Høiby N: Antibiotic resistance in P. aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob. Agents Chemother. 53, 2483-2491 (2009).
95. Oliver A, Baquero F, Blazquez J: The mismatch repair system (MutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants. Mol. Microbiol. 43(6), 1641-1650 (2002).
96. Ciofu O, Mandsberg LF, Bjarnsholt T, Wassermann T, Høiby N: Genetic adaptation of P. aeruginosa during chronic lung infection: strong and weak mutators with heterogenous backgrounds emerge in mucA and/or lasR mutants. Microbiology 156, 1108-1119 (2010).
97. Macia MD, Borrell N, Perez JL, Oliver A: Detection and susceptibility testing of hypermutable Pseudomonas aeruginosa strains with the Etest and disk diffusion. Antimicrob. Agents Chemother. 48(7), 2665-2672 (2004).
98. Macia MD, Blanquer D, Togores B, Sauleda J, Perez JL, Oliver A: Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections. Antimicrob. Agents Chemother. 49(8), 3382-3386 (2005).
99. Driffeld K, Miller K, Bostock M, O'Neill AJ, Chopra I: Increased mutability of Pseudomonas aeruginosa in bioflms. J. Antimicrob. Chemother. 61, 1053-1056 (2008).
100. Stover CK, Pham XQ, Erwin AL et al.: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406(6799), 959-964 (2000).
101. Smith EE, Buckley DG, Wu Z et al.: Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl Acad. Sci. USA 1-6 (2006).
102. Döring G, Høiby N: Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J. Cystic Fibrosis 3, 67-91 (2004).
103. Proesmans M, Balinska-Miskiewicz W, Dupont L et al.: Evaluating the "Leeds criteria" for Pseudomonas aeruginosa infection in a cystic fibrosis centre. Eur. Resp. J. 2 7, 937-943 (2006).
104. Pressler T, Frederiksen B, Skov M, Garred P, Koch C, Høiby N: Early rise of anti-Pseudomonas antibodies and a mucoid phenotype of Pseudomonas aeruginosa are risk factors for development of chronic lung infection - a case control study. J. Cystic Fibrosis 5, 9-15 (2006).
105. Høiby N, Frederiksen B, Pressler T: Eradication of early Pseudomonas aeruginosa infection. J. Cystic Fibrosis 4, 49-54 (2005).
106. Hansen CR, Pressler T, Høiby N: Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience. J. Cystic Fibrosis 7, 523-530 (2008).
107. Döring G, Conway SP, Heijerman HGM et al.: Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur. Resp. J. 16, 749-767 (2000).
108. Rasmussen TB, Bjarnsholt T, Skindersoe ME et al.: Screening for quorum sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J. Bacteriol. 187, 1799-1814 (2005).
109. Parks QM, Young RL, Poch KR, Malcolm KC, Vasil ML, Nick JA: Neutrophil enhancement of Pseudomonas aeruginosa bioflm development: human F-actin and DNA as targets for therapy. J. Med. Microbiol. 58, 492-502 (2009).
110. Tolker-Nielsen T, Høiby N: Extracellular DNA and F-actin as targets in anti-bioflm CF therapy. Future Microbiol. 4, 645-647 (2009).
111. Ciofu O, Petersen TD, Jensen P, Høiby N: Avidity of anti-P aeruginosa antibodies during chronic infection in patients with cystic fibrosis. Thorax 54(2), 141-144 (1999). (Pubitemid 29101358)
112. Ciofu O, Bagge N, Høiby N: Antibodies against b-lactamase can improve ceftazidime treatment of lung infection with b-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection. APMIS 110(12), 881-891 (2002).
113. Ciofu O: Pseudomonas aeruginosa chromosomal b-lactamase in patients with cystic fibrosis and chronic lung infection - mechanism of antibiotic resistance and target of the humoral immune response. APMIS 111, 4-47 (2003).
114. Kobayashi H: Bioflm disease: its clinical manifestation and therapeutic possibilities of macrolides. Am. J. Med. 99(Suppl. 6A Pt 1), S26-S30 (1995).
115. Tateda K, Comte R, Pechere JC, Kohler T, Yamaguchi K, VanDelden C: Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 45(6), 1930-1933 (2001). (Pubitemid 32466379)