Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 362, Issue 1483, 2007, Pages 1213-1222

  Bjarnsholt, Thomas ^a   Givskov, Michael ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

Biofilms; Cystic fibrosis; Pseudomonas aeruginosa; Quorum sensing; Quorum sensing inhibition

Indexed keywords

ANTIBIOTIC RESISTANCE; ANTIBIOTICS; APOPTOSIS; BACTERIUM; BIOFILM; DEFENSE MECHANISM; PATHOGEN; PATHOGENICITY; VIRULENCE;

BACTERIA (MICROORGANISMS); PSEUDOMONAS AERUGINOSA;

EID: 34447580199     PISSN: 09628436     EISSN: None     Source Type: Journal    
DOI: 10.1098/rstb.2007.2046     Document Type: Review

References (99)

1. Allesen-Holm, M., Barken Bundvig, K., Yang, L., Klausen, M., Webb, J. S., Kjelleberg, S., Molin, S., Givskov, M. & Tolker-Nielsen, T. 2005 A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol. Microbiol. 54, 1114-1128.
2. Ankri, S. & Mirelman, D. 1999 Antimicrobial properties of allicin from garlic. Microbes Infect. 1, 125-129. (doi:10. 1016/S1286-4579(99)80003-3)
3. Anthony, M., Kjelleberg, S., Kumar, N., de Nys, R., Read, R. & Stainberg, P. 1997 Reinvestigation of the sulfuric acid-catalysed cyclisation of brominated 2-alkylllevulinic acids to 3-alkyl-5-methylene-2(5H)- furanones. Tetrahedron 53, 15 813-15 826. (doi:10.1016/S0040- 4020(97)10034-5)
4. Baltimore, R. S., Christie, C. D. & Smith, G. J. 1989 Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration. Am. Rev. Respir. Dis. 140, 1650-1661.
5. Bauernfeind, A., Bertele, R. M., Harms, K., Horl, G., Jungwirth, R., Petermuller, C., Przyklenk, B. & Weisslein-Pfister, C. 1987 Qualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis. Infection 15, 270-277. (doi:10.1007/BF01644137)
6. Beatson, S. A., Whitchurch, C. B., Semmler, A. B. & Mattick, J. S. 2002 Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J. Bacteriol. 184, 3598-3604. (doi:10.1128/JB.184.13. 3598-3604.2002)
7. Bjarnsholt, T. et al. 2005a Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151, 373-383. (doi:10.1099/mic.0.27463-0)
8. Bjarnsholt, T. et al. 2005b Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 151, 3873-3880. (doi:10. 1099/mic.0.27955-0)
9. Boucher, R. C. 2002 An overview of the pathogenesis of cystic fibrosis lung disease. Adv. Drug Deliv. Rev. 54, 1359-1371. (doi:10.1016/S0169-409X(02)00144-8)
10. Collier, D. N., Anderson, L., McKnight, S. L., Noah, T. L., Knowles, M., Boucher, R., Schwab, U., Gilligan, P. & Pesci, E. C. 2002 A bacterial cell to cell signal in the lungs of cystic fibrosis patients. FEMS Microbiol. Lett. 215, 41. (doi:10.1111/j.1574-6968.2002.tb11367.x)
11. Cox, C. D. 1982 Effect of pyochelin on the virulence of Pseudomonas aeruginosa. Infect. Immun. 36, 17-23.
12. Davies, D. G., Parsek, M. R., Pearson, J. P., Iglewski, B. H., Costerton, J. W. & Greenberg, E. P. 1998a The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295-298. (doi:10.1126/ science.280.5361.295)
13. Davies, D. G., Parsek, M. R., Pearson, J. P., Iglewski, B. H., Costerton, J. W. & Greenberg, E. P. 19986 The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295-298. (doi:10.1126/ science.280.5361.295)
14. de Nys, R., Wright, A. D., Konig, G. M. & Sticher, O. 1993 New halogenated furanones from the marine alga Delisea pulchra. Tetrahedron 49, 11213-11220. (doi:10.1016/ S0040-4020(01)81808-1)
15. Donaldson, S. H. & Boucher, R. C. 2003 Update on pathogenesis of cystic fibrosis lung disease. Curr. Opin. Pulm. Med. 9, 486-491. (doi:10.1097/00063198-200311 000-00007)
16. Donlan, R. M. & Costerton, J. W. 2002 Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 15, 167-193. (doi:10.1128/CMR.15.2. 167-193.2002)
17. Eberl, L. et al. 1996 Involvement of N-acyl-L- hormoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens. Mol. Microbiol. 20, 127-136. (doi:10.1111/j.1365-2958.1996.tb02495.x)
18. Erickson, D. L., Endersby, R., Kirkham, A., Stuber, K., Vollman, D. D., Rabin, H. R., Mitchell, I. & Storey, D. G. 2002 Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect. Immun. 70, 1783-1790. (doi:10.1128/IAI.70.4.1783-1790.2002)
19. Favre-Bonte, S., Pache, J. C., Robert, J., Blanc, D., Pechere, J. C. & van Delden, C. 2002 Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients. Microb. Pathog. 32, 143-147. (doi:10. 1006/mpat.2001.0487)
20. 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, 330-335. (doi:10.1002/(SICI)1099- 0496(199705)23:5〈 330::AID-PPUL4〉3.0.CO;2-O)
21. Fruhwirth, M., Ruedl, C., Ellemunter, H., Bock, G. & Wolf, H. 1998 Flow-cytometric evaluation of oxidative burst in phagocytic cells of children with cystic fibrosis. Int. Arch. Allergy Immunol. 17, 270-275.
22. Fuqua, C., Parsek, M. R. & Greenberg, E. P. 2001 Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu. Rev. Genet. 35, 439-468. (doi:10.1146/annurev. genet.35. 102401.090913)
23. Geisenberger, O., Givskov, M., Riedel, K., Hoiby, N., Tummler, B. & Eberl, L. 2000 Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis. FEMS Microbiol. Lett. 184, 273-278.
24. Gibson, R. L., Burns, J. L. & Ramsey, B. W. 2003 Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168, 918-951. (doi:10.1164/rccm.200304-505SO)
25. Gilligan, P. H. 1991 Microbiology of airway disease in patients with cystic fibrosis. Clin. Microbiol. Rev. 4, 35-51.
26. Givskov, M., de Nys, R., Manefield, M., Gram, L., Maximilien, R., Eberl, L., Molin, S., Steinberg, P. D. & Kjelleberg, S. 1996 Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J. Bacteriol. 178, 6618-6622.
27. Glessner, A., Smith, R. S., Iglewski, B. H. & Robinson, J. B. 1999 Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of twitching motility. J. Bacteriol. 181, 1623-1629.
28. Haagensen, J. A., Klausen, M., Tolker-Nielsen, T., Ernst, R. K., Miller, S. I. & Molin, S. 2007 Differentiation and distribution of colistin/SDS tolerant cells in Pseudomonas aeruginosa flow-cell biofilms. J. Bacteriol. 189, 28-37.
29. Hall-Stoodley, L., Costerton, J. W. & Stoodley, P. 2004 Bacterial biofilms: from the natural environment to infectious diseases. Nat. Rev. Microbiol. 2, 95-108. (doi:10.1038/nrmicro821)
30. Hentzer, M. et al. 2002 Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148, 87-102.
31. Hentzer, M. et al. 2003 Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J. 22, 3803-3815. (doi:10.1093/emboj/cdg366)
32. Hentzer, M., Givskov, M. & Eberl, L. 2004 Quorum sensing in biofilms: gossip in the slime city. In Microbial biofilms (eds G. Mahmoud & G. O'Toole), pp. 118-140. Washington, DC: ASM Press.
33. Hentzer, M., Eberl, L. & Givskov, M. 2005 Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2, 37-61. (doi:10.1017/ S1479050505001699)
34. Heydorn, A., Ersboll, B., Kato, J., Hentzer, M., Parsek, M. R., Tolker-Nielsen, T., Givskov, M. & Molin, S. 2002 Statistical analysis of Pseudomonas aeruginosa biofilm development: impact of mutations in genes involved in twitching motility, cell-to-cell signaling, and stationary-phase sigma factor expression. Appl. Environ. Microbiol. 68, 2008-2017. (doi:10.1128/AEM.68.4.2008-2017.2002)
35. Hjelmgaard, T., Persson, T., Rasmussen, T. B., Givskov, M. & Nielsen, J. 2003 Synthesis of furanone-based natural product analogues with quorum sensing antagonist activity. Bioorg. Med. Chem. 11, 3261-3271. (doi:10. 1016/S0968-0896(03)00295-5)
36. Hoiby, N. 1974 Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis. Acta Pathol. Microbiol. Immunol. Scand. B 82, 541-550.
37. Hoiby, N. 1977 Pseudomonas aeruginosa infection in cystic fibrosis. Doctoral thesis, University of Copenhagen.
38. Howe, T. R. & Iglewski, B. H. 1984 Isolation and characterization of alkaline protease-deficient mutants of Pseudomonas aeruginosa in vitro and in a mouse eye model. Infect. Immun. 43, 1058-1063.
39. Huang, J. J., Han, J. I., Zhang, L. H. & Leadbetter, J. R. 2003 Utilization of acyl-homoserine lactone quorum signals for growth by a soil pseudomonad and Pseudomonas aeruginosa PAO1. Appl. Environ. Microbiol. 69, 5941-5949. (doi:10.1128/AEM.69.10.5941-5949.2003)
40. Huang, J. J., Petersen, A., Whiteley, M. & Leadbetter, J. R. 2006 Identification of QuiP, the product of gene PA1032, as the second acyl-homoserine lactone acylase of Pseudomonas aeruginosa PAO1. Appl. Environ. Microbiol. 72, 1190-1197. (doi:10.1128/AEM.72.2.1190-1197. 2006)
41. Ichimiya, T., Takeoka, K., Hiramatsu, K., Hirai, K., Yamasaki, T. & Nasu, M. 1996 The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro. Chemotherapy 42, 186-191.
42. Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M. & Tsui, L. C. 1989 Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080. (doi:10.1126/ science.2570460)
43. Kjelleberg, S. & Molin, S. 2002 Is there a role for quorum sensing signals in bacterial biofilms? Curr. Opin. Microbiol. 5, 254-258. (doi:10.1016/S1369-5274(02)00325-9)
44. Kjelleberg, S., Steinberg, P., Givskov, M., Gram, L., Manefield, M. & de Nys, R. 1997 Do marine natural products interfere with prokeryotic AHL regulatory systems? Aquat. Microb. Ecol. 13, 85-93.
45. Knowles, M. R. & Boucher, R. C. 2002 Mucus clearance as a primary innate defense mechanism for mammalian airways. J. Clin. Invest. 109, 571-577. (doi:10.1172/JCI2 00215217)
46. Kobayashi, H. 2005 Airway biofilms: implications for pathogenesis and therapy of respiratory tract infections. Treat. Respir. Med. 4, 241-253. (doi:10.2165/00151829-200504040-00003)
47. Koch, C. 2002 Early infection and progression of cystic fibrosis lung disease. Pediatr. Pulmonol. 34, 232-236. (doi:10.1002/ppul.10135)
48. Koch, C. & Hoiby, N. 1993 Pathogenesis of cystic fibrosis. Lancet 341, 1065-1069. (doi:10.1016/0140-6736(93) 92422-P)
49. Koch, C. & Hoiby, N. 2000 Diagnosis and treatment of cystic fibrosis. Respiration 67, 239-247. (doi:10.1159/000029503)
50. Konstan, M. W., Krenicky, J. E., Finney, M. R., Kirchner, H. L., Hilliard, K. A., Hilliard, J. B., Davis, P. B. & Hoppel, C. L. 2003 Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and healthy subjects. J. Pharmacol. Exp. Ther. 306, 1086-1091. (doi:10.1124/ jpet.103.052449)
51. Lam, J., Chan, R., Lam, K. & Costerton, J. W. 1980 Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect. Immun. 28, 546-556.
52. Lawrence, R. N., Dunn, W. R., Bycroft, B., Camara, M., Chhabra, S. R., Williams, P. & Wilson, V. G. 1999 The Pseudomonas aeruginosa quorum-sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, inhibits porcine arterial smooth muscle contraction. Br. J. Pharmacol. 128, 845-848. (doi:10.1038/sj.bjp.0702870)
53. Manefield, M. & Turner, S. L. 2002 Quorum sensing in context: out of molecular biology and into microbial ecology. Microbiology 148, 3762-3764.
54. Manefield, M., Rasmussen, T. B., Henzter, M., Andersen, J. B., Steinberg, P., Kjelleberg, S. & Givskov, M. 2002 Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 148, 1119-1127.
55. Middleton, B., Rodgers, H. C., Camara, M., Knox, A. J., Williams, P. & Hardman, A. 2002 Direct detection of N-acylhomoserine lactones in cystic fibrosis sputum. FEMS Microbiol. Lett. 207, 1-7. (doi:10.1111/j.1574-6968.2002.tb11019.x)
56. Murray, P. R., Rosenthal, K. S., Kobayashi, G. S. & Pfaller, M. A. 2002 Medical microbiology, 4th edn. St. Louis, MO: Mosby.
57. National Institutes of Health 2004 The problem of antibiotic resistance. See http://www.niaid.nih.gov/factsheets/antimicro.htm.
58. Nicas, T. I., Frank, D. W., Stenzel, P., Lile, J. D. & Iglewski, B. H. 1985 Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections. Eur. J. Clin. Microbiol. 4, 175-179. (doi:10.1007/BF02013593)
59. Nilsson, P., Olofsson, A., Fagerlind, M., Fagerstrom, T., Rice, S., Kjelleberg, S. & Steinberg, P. 2001 Kinetics of the AHL regulatory system in a model biofilm system: how many bacteria constitute a "quorum"? J. Mol. Biol. 309, 631-640. (doi:10.1006/jmbi.2001.4697)
60. Norrby, S. R., Nord, C. E. & Finch, R. 2005 Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect. Dis. 5, 115-119.
61. Pearson, J. P., Pesci, E. C. & Iglewski, B. H. 1997 Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes. J. Bacteriol. 179, 5756-5767.
62. Pearson, J. P., Feldman, M., Iglewski, B. H. & Prince, A. 2000 Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect. Immun. 68, 4331-4334. (doi:10.1128/ IAI.68.7.4331-4334.2000)
63. Pedersen, S. S., Hoiby, N., Espersen, F. & Koch, C. 1992 Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. Thorax 47, 6-13.
64. Pesci, E. C., Pearson, J. P., Seed, P. C. & Iglewski, B. H. 1997 Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J. Bacteriol. 179, 3127-3132.
65. Potts, S. B., Roggli, V. L. & Spock, A. 1995 Immunohistologic quantification of Pseudomonas aeruginosa in the tracheobronchial tree from patients with cystic fibrosis. Pediatr. Pathol. Lab. Med. 15, 707-721.
66. Preston, M. J., Seed, P. C., Toder, D. S., Iglewski, B. H., Ohman, D. E., Gustin, J. K., Goldberg, J. B. & Pier, G. B. 1997 Contribution of proteases and LasR to the virulence of Pseudomonas aeruginosa during corneal infections. Infect. Immun. 65, 3086-3090.
67. Rasch, M. et al. 2004 An inhibitor of bacterial quorum sensing reduces mortalities caused by vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum). Syst. Appl. Microbiol. 27, 350-359. (doi:10.1078/0723-2020-00268)
68. Rasmussen, T. B., Bjarnsholt, T., Skindersoe, M. E., Hentzer, M., Kristoffersen, P., Kote, M., Eberl, L., Nielsen, J. & Givskov, M. 2005a Screening for quorum sensing inhibitors using a novel genetic system - the QSI selector. J. Bacteriol. 187, 1799-1814. (doi:10.1128/JB. 187.5.1799-1814.2005)
69. Rasmussen, T. B., Skindersoe, M. E., Bjarnsholt, T., Christensen, K. B., Andersen, J. B., Ostenfeld-Larsen, T., Hentzer, M. & Givskov, M. 20056 Identity and effects of quorum sensing inhibitors produced by Penicillum species. Microbiology 151, 1325-1340. (doi:10.1099/mic.0. 27715-0)
70. Riordan, J. R. et al. 1989 Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073. (doi:10.1126/science. 2475911)
71. Rommens, J. M. et al. 1989 Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245, 1059-1065. (doi:10.1126/science.2772657)
72. Rubenstein, R. C. 2005 Novel, mechanism-based therapies for cystic fibrosis. Curr. Opin. Pediatr. 17, 385-392. (doi:10.1097/01.mop. 0000158846.95469.6f)
73. Rumbaugh, K. P., Griswold, J. A., Iglewski, B. H. & Hamood, A. N. 1999 Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections. Infect. Immun. 67, 5854-5862.
74. Rumbaugh, K. P., Griswold, J. A. & Hamood, A. N. 2000 The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa. Microbes Infect. 2, 1721-1731. (doi:10.1016/S1286-4579(00)01327-7)
75. Saiman, L. 2004a Microbiology of early CF lung disease. Paediatr. Respir. Rev. 5, S367-S369. (doi:10.1016/S1526-0542(04) 90065-6)
76. Saiman, L. 2004b The use of macrolide antibiotics in patients with cystic fibrosis. Curr. Opin. Pulm. Med. 10, 515-523. (doi:10.1097/01.mcp.0000142101.53084.f0)
77. Schuster, M., Lostroh, C. P., Ogi, T. & Greenberg, E. P. 2003 Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J. Bacteriol. 185, 2066-2079. (doi:10.1128/JB. 185.7.2066-2079.2003)
78. Singh, P. K., Schaefer, A. L., Parsek, M. R., Moninger, T. O., Welsh, M. J. & Greenberg, E. P. 2000 Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407, 762-764. (doi:10.1038/ 35037627)
79. Southern, K. W. & Barker, P. M. 2004 Azithromycin for cystic fibrosis. Eur. Respir. J. 24, 834-838. (doi:10.1183/ 09031936.04.00084304)
80. Storey, D. G., Ujack, E. E., Rabin, H. R. & Mitchell, I. 1998 Pseudomonas aeruginosa lasR transcription correlates with the transcription of lasA, lasB, and toxA in chronic lung infections associated with cystic fibrosis. Infect. Immun. 66, 2521-2528.
81. Stover, C. K. et al. 2000 Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406, 959-964. (doi:10.1038/35023079)
82. Taga, M. E. & Bassler, B. L. 2003 Chemical communication among bacteria. Proc. Natl Acad. Sci. USA 100, 14 549-14 554. (doi:10.1073/pnas.1934514100)
83. Tang, H., Kays, M. & Prince, A. 1995 Role of Pseudomonas aeruginosa pili in acute pulmonary infection. Infect. Immun. 63, 1278-1285.
84. Tang, H. B., DiMango, E., Bryan, R., Gambello, M., Iglewski, B. H., Goldberg, J. B. & Prince, A. 1996 Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infect. Immun. 64, 37-43.
85. Tateda, K., Comte, R., Pechere, J. C., Kohler, T., Yamaguchi, K. & van Delden, C. 2001 Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 45, 1930-1933. (doi:10. 1128/AAC.45.6.1930-1933.2001)
86. van Delden, C. & Iglewski, B. H. 1998 Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg. Infect. Dis. 4, 551-560.
87. van Delden, C., Comte, R. & Bally, A. M. 2001 Stringent response activates quorum sensing and modulates cell density-dependent gene expression in Pseudomonas aeruginosa. J. Bacteriol. 183, 5376-5384. (doi:10.1128/ JB.183.18.5376-5384.2001)
88. Vasil, M. L., Grant, C. C. & Prince, R. W. 1989 Regulation of exotoxin A synthesis in Pseudomonas aeruginosa: characterization of toxA-lacZ fusions in wild-type and mutant strains. Mol. Microbiol. 3, 371-381. (doi:10.1111/j.1365-2958.1989.tb00182.x)
89. Vasil, M. L., Graham, L. M., Ostroff, R. M., Shortridge, V. D. & Vasil, A. I. 1991 Phospholipase C: molecular biology and contribution to the pathogenesis of Pseudomonas aeruginosa. Antibiot. Chemother. 44, 34-47.
90. Wagner, V. E., Bushnell, D., Passador, L., Brooks, A. I. & Iglewski, B. H. 2003 Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J. Bacteriol. 185, 2080-2095. (doi:10.1128/JB.185.7.2080-2095.2003)
91. Williams, P. et al. 2000 Quorum sensing and the population-dependent control of virulence. Phil. Trans. R. Soc. B 355, 667-680. (doi:10.1098/rstb.2000.0607)
92. Williams, P., Winzer, K., Chan, W. & Cámara, M. 2007 Look who's talking: communication and quorum sensing in the bacterial world. Phil. Trans. R. Soc. B 362, 1119-1134. (doi:10.1098/rstb.2007.2039)
93. Woods, D. E., Cryz, S. J., Friedman, R. L. & Iglewski, B. H. 1982 Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect. Immun. 36, 1223-1228.
94. Worlitzsch, D. et al. 2002 Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Invest. 109, 317-325. (doi:10. 1172/JCI200213870)
95. Worlitzsch, D., Ulrich, M., Bragonzi, A., Viglio, S., Weidemann, B. & Doring, G. 2004 Alveolar tissue destruction by macrophages and neutrophils in cystic fibrosis. Pediatr. Pulmonol. 27(Suppl.), 277. Abstract.
96. Wu, H. et al. 2000 Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa. Microbiology 146, 2481-2493.
97. Wu, H., Song, Z., Givskov, M., Doring, G., Worlitzsch, D., Mathee, K., Rygaard, J. & Hoiby, N. 2001 Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection. Microbiology 147, 1105-1113.
98. Wu, H., Song, Z., Givskov, M. & Hoiby, N. 2004a Effects of quorum-sensing on immunoglobulin G responses in a rat model of chronic lung infection with Pseudomonas aeruginosa. Microbes Infect. 6, 34-37. (doi:10.1016/j.micinf. 2003.10.006)
99. Wu, H., Song, Z., Hentzer, M., Andersen, J. B., Molin, S., Givskov, M. & Hoiby, N. 20046 Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J. Antimicrob. Chemother. 53, 1054-1061. (doi:10.1093/ jac/dkh223)