Review

Targeting quorum sensing in Pseudomonas aeruginosa biofilms: current and emerging inhibitors

Costerton Biofilm Center, Department of International Health, Immunology & Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark

Search for more papers by this author

Thomas Bjarnsholt

Costerton Biofilm Center, Department of International Health, Immunology & Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark

Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen, Denmark

Search for more papers by this author

Peter Østrup Jensen

Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen, Denmark

Search for more papers by this author

Michael Givskov

Costerton Biofilm Center, Department of International Health, Immunology & Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark

Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore

Search for more papers by this author

Niels Høiby

* Author for correspondence

Costerton Biofilm Center, Department of International Health, Immunology & Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark. .

Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen, Denmark

Search for more papers by this author

Email the corresponding author at hoiby@hoibyniels.dk

Published Online:10 Jul 2013https://doi.org/10.2217/fmb.13.57

View article

Abstract

Bacterial resistance to conventional antibiotics combined with an increasing acknowledgement of the role of biofilms in chronic infections has led to a growing interest in new antimicrobial strategies that target the biofilm mode of growth. In the aggregated biofilm mode, cell-to-cell communication systems involved in the process known as quorum sensing regulate coordinated expression of virulence with immune shielding mechanisms and antibiotic resistance. For two decades, the potential of interference with quorum sensing by small chemical compounds has been investigated with the aim of developing alternative antibacterial strategies. Here, we review state of the art research of quorum sensing inhibitors against the opportunistic human pathogen Pseudomonas aeruginosa, which is found in a number of biofilm-associated infections and identified as the predominant organism infecting the lungs of cystic fibrosis patients.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Nealson KH, Platt T, Hastings JW. Cellular control of the synthesis and activity of the bacterial luminescent system. J. Bacteriol.104(1),313–322 (1970).Crossref, Medline, CAS, Google Scholar
2 Bjarnsholt T, Givskov M. The role of quorum sensing in the pathogenicity of the cunning aggressor Pseudomonas aeruginosa. Anal. Bioanal. Chem.387(2),409–414 (2007).Crossref, Medline, CAS, Google Scholar
3 Costerton JW. Introduction to biofilm. Int. J. Antimicrob. Agents11(3–4),217–221; discussion 237–219 (1999).Crossref, Medline, CAS, Google Scholar
4 Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM. Microbial biofilms. Annu. Rev. Microbiol.49,711–745 (1995).Crossref, Medline, CAS, Google Scholar
5 Potera C. Studying slime. Environ. Health Persp.106(12),A604–A606 (1998).Crossref, Medline, CAS, Google Scholar
6 Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int. J. Antimicrob. Agents35(4),322–332 (2010).Crossref, Medline, Google Scholar
7 Gomez MI, Prince A. Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr. Opin. Pharmacol.7(3),244–251 (2007).Crossref, Medline, CAS, Google Scholar
8 Stover CK, Pham XQ, Erwin AL et al. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature406(6799),959–964 (2000).Crossref, Medline, CAS, Google Scholar
9 Hassett DJ, Cuppoletti J, Trapnell B et al. Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Adv. Drug Deliv. Rev.54(11),1425–1443 (2002).Crossref, Medline, CAS, Google Scholar
10 Lyczak JB, Cannon CL, Pier GB. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect.2(9),1051–1060 (2000).Crossref, Medline, CAS, Google Scholar
11 Obritsch MD, Fish DN, MacLaren R, Jung R. Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options. Pharmacotherapy25(10),1353–1364 (2005).Crossref, Medline, CAS, Google Scholar
12 Woodward TC, Brown R, Sacco P, Zhang J. Budget impact model of tobramycin inhalation solution for treatment of Pseudomonas aeruginosa in cystic fibrosis patients. J. Med. Econ.13(3),492–499 (2010).Crossref, Medline, Google Scholar
13 Koch C, Hoiby N. Pathogenesis of cystic fibrosis. Lancet341(8852),1065–1069 (1993).Crossref, Medline, CAS, Google Scholar
14 Taga ME, Bassler BL. Chemical communication among bacteria. Proc. Natl Acad. Sci. USA100(Suppl. 2),S14549–S14554 (2003).Crossref, Medline, CAS, Google Scholar
15 Fuqua C, Parsek MR, Greenberg EP. Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu. Rev. Genet.35,439–468 (2001).Crossref, Medline, CAS, Google Scholar
16 Fuqua C, Greenberg EP. Listening in on bacteria: acyl-homoserine lactone signalling. Nat. Rev. Mol. Cell Biol.3(9),685–695 (2002).Crossref, Medline, CAS, Google Scholar
17 Miller MB, Bassler BL. Quorum sensing in bacteria. Annu. Rev. Microbiol.55,165–199 (2001).Crossref, Medline, CAS, Google Scholar
18 Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR–LuxI family of cell density-responsive transcriptional regulators. J. Bacteriol.176(2),269–275 (1994).Crossref, Medline, CAS, Google Scholar
19 Pearson JP, Gray KM, Passador L et al. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc. Natl Acad. Sci. USA91(1),197–201 (1994).Crossref, Medline, CAS, Google Scholar
20 Pearson JP, Passador L, Iglewski BH, Greenberg EP. A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA92(5),1490–1494 (1995).Crossref, Medline, CAS, Google Scholar
21 Pesci EC, Milbank JB, Pearson JP et al. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA96(20),11229–11234 (1999).Crossref, Medline, CAS, Google Scholar
22 Deziel E, Lepine F, Milot S et al. Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication. Proc. Natl Acad. Sci. USA101(5),1339–1344 (2004).Crossref, Medline, CAS, Google Scholar
23 Wade DS, Calfee MW, Rocha ER et al. Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa. J. Bacteriol.187(13),4372–4380 (2005).Crossref, Medline, CAS, Google Scholar
24 Gallagher LA, McKnight SL, Kuznetsova MS, Pesci EC, Manoil C. Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa. J. Bacteriol.184(23),6472–6480 (2002).Crossref, Medline, CAS, Google Scholar
25 McGrath S, Wade DS, Pesci EC. Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS). FEMS Microbiol. Lett.230(1),27–34 (2004).Crossref, Medline, CAS, Google Scholar
26 Xiao G, He J, Rahme LG. Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry. Microbiology152(Pt 6),1679–1686 (2006).Crossref, Medline, CAS, Google Scholar
27 Diggle SP, Winzer K, Chhabra SR, Worrall KE, Camara M, Williams P. The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR. Mol. Microbiol.50(1),29–43 (2003).Crossref, Medline, CAS, Google Scholar
28 Juhas M, Eberl L, Tummler B. Quorum sensing: the power of cooperation in the world of Pseudomonas. Environ. Microbiol.7(4),459–471 (2005).Crossref, Medline, CAS, Google Scholar
29 Pesci EC, Pearson JP, Seed PC, Iglewski BH. Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J. Bacteriol.179(10),3127–3132 (1997).Crossref, Medline, CAS, Google Scholar
30 Schuster M, Lostroh CP, Ogi T, Greenberg EP. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J. Bacteriol.185(7),2066–2079 (2003).Crossref, Medline, CAS, Google Scholar
31 Hentzer M, Wu H, Andersen JB et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J.22(15),3803–3815 (2003).▪▪ First study using transcriptomic analysis to evaluate a quorum sensing (QS) inhibitor (QSI).Crossref, Medline, CAS, Google Scholar
32 Wagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J. Bacteriol.185(7),2080–2095 (2003).Crossref, Medline, CAS, Google Scholar
33 Howe TR, Iglewski BH. Isolation and characterization of alkaline protease-deficient mutants of Pseudomonas aeruginosa in vitro and in a mouse eye model. Infect. Immun.43(3),1058–1063 (1984).Crossref, Medline, CAS, Google Scholar
34 Woods DE, Cryz SJ, Friedman RL, Iglewski BH. Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect. Immun.36(3),1223–1228 (1982).Crossref, Medline, CAS, Google Scholar
35 Vasil ML, Grant CC, Prince RW. Regulation of exotoxin A synthesis in Pseudomonas aeruginosa: characterization of toxA–lacZ fusions in wild-type and mutant strains. Mol. Microbiol.3(3),371–381 (1989).Crossref, Medline, CAS, Google Scholar
36 Nicas TI, Frank DW, Stenzel P, Lile JD, Iglewski BH. Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections. Eur. J. Clin. Microbiol.4(2),175–179 (1985).Crossref, Medline, CAS, Google Scholar
37 Cox CD. Effect of pyochelin on the virulence of Pseudomonas aeruginosa. Infect. Immun.36(1),17–23 (1982).Crossref, Medline, CAS, Google Scholar
38 Jensen PO, Bjarnsholt T, Phipps R et al. Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology153(Pt 5),1329–1338 (2007).▪ Investigation documenting the QS-regulated rhamnolipid as an important virulence factor towards the immune defense system.Crossref, Medline, CAS, Google Scholar
39 McClure CD, Schiller NL. Effects of Pseudomonas aeruginosa rhamnolipids on human monocyte-derived macrophages. J. Leukocyte Biol.51(2),97–102 (1992).Crossref, Medline, CAS, Google Scholar
40 Shryock T, Silver S, Banschbach M, Kramer J. Effect of Pseudomonas aeruginosa rhamnolipid on human neutrophil migration. Curr. Microbiol.10(6),323–328 (1984).Crossref, CAS, Google Scholar
41 Déziel E, Lépine F, Milot S, Villemur R. rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs), the precursors of rhamnolipids. Microbiology149(Pt 8),2005–2013 (2003).Crossref, Medline, CAS, Google Scholar
42 Hentzer M, Eberl L, Givskov M. Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms2(1),37–61 (2005).Crossref, Google Scholar
43 Williams P, Camara M. Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr. Opin. Microbiol.12(2),182–191 (2009).Crossref, Medline, CAS, Google Scholar
44 Schuster M, Greenberg EP. A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J. Med. Microbiol.296(2–3),73–81 (2006).Crossref, Medline, CAS, Google Scholar
45 Lequette Y, Lee JH, Ledgham F, Lazdunski A, Greenberg EP. A distinct QscR regulon in the Pseudomonas aeruginosa quorum-sensing circuit. J. Bacteriol.188(9),3365–3370 (2006).Crossref, Medline, CAS, Google Scholar
46 Chugani SA, Whiteley M, Lee KM, D’Argenio D, Manoil C, Greenberg EP. QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA98(5),2752–2757 (2001).Crossref, Medline, CAS, Google Scholar
47 Ledgham F, Ventre I, Soscia C, Foglino M, Sturgis JN, Lazdunski A. Interactions of the quorum sensing regulator QscR: interaction with itself and the other regulators of Pseudomonas aeruginosa LasR and RhlR. Mol. Microbiol.48(1),199–210 (2003).Crossref, Medline, CAS, Google Scholar
48 Lee JH, Lequette Y, Greenberg EP. Activity of purified QscR, a Pseudomonas aeruginosa orphan quorum-sensing transcription factor. Mol. Microbiol.59(2),602–609 (2006).Crossref, Medline, CAS, Google Scholar
49 Juhas M, Wiehlmann L, Huber B et al. Global regulation of quorum sensing and virulence by VqsR in Pseudomonas aeruginosa. Microbiology150(Pt 4),831–841 (2004).Crossref, Medline, CAS, Google Scholar
50 Li LL, Malone JE, Iglewski BH. Regulation of the Pseudomonas aeruginosa quorum-sensing regulator VqsR. J. Bacteriol.189(12),4367–4374 (2007).Crossref, Medline, CAS, Google Scholar
51 Liang H, Deng X, Ji Q, Sun F, Shen T, He C. The Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression. J. Bacteriol.194(12),3098–3108 (2012).Crossref, Medline, CAS, Google Scholar
52 Albus AM, Pesci EC, Runyen-Janecky LJ, West SE, Iglewski BH. Vfr controls quorum sensing in Pseudomonas aeruginosa. J. Bacteriol.179(12),3928–3935 (1997).Crossref, Medline, CAS, Google Scholar
53 West SE, Sample AK, Runyen-Janecky LJ. The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family. J. Bacteriol.176(24),7532–7542 (1994).Crossref, Medline, CAS, Google Scholar
54 Croda -Garcia G, Grosso-Becerra V, Gonzalez-Valdez A, Servin-Gonzalez L, Soberon-Chavez G. Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR and RhlR. Microbiology157(Pt 9),2545–2555 (2011).Crossref, Medline, Google Scholar
55 Rampioni G, Schuster M, Greenberg EP et al. RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa. Mol. Microbiol.66(6),1557–1565 (2007).Crossref, Medline, CAS, Google Scholar
56 Venturi V, Rampioni G, Pongor S, Leoni L. The virtue of temperance: built-in negative regulators of quorum sensing in Pseudomonas. Mol. Microbiol.82(5),1060–1070 (2011).Crossref, Medline, CAS, Google Scholar
57 Reimmann C, Beyeler M, Latifi A et al. 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(2),309–319 (1997).Crossref, Medline, CAS, Google Scholar
58 Kay E, Humair B, Denervaud V et al. Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa. J. Bacteriol.188(16),6026–6033 (2006).Crossref, Medline, CAS, Google Scholar
59 Pessi G, Williams F, Hindle Z et al. The global posttranscriptional regulator RsmA modulates production of virulence determinants and N-acylhomoserine lactones in Pseudomonas aeruginosa. J. Bacteriol.183(22),6676–6683 (2001).Crossref, Medline, CAS, Google Scholar
60 Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science284(5418),1318–1322 (1999).▪▪ Important review with a description of the biofilm concept.Crossref, Google Scholar
61 O ’Toole G, Kaplan HB, Kolter R. Biofilm formation as microbial development. Annu. Rev. Microbiol.54,49–79 (2000).Crossref, Medline, Google Scholar
62 Sauer K. The genomics and proteomics of biofilm formation. Genome Biol.4(6),219 (2003).Crossref, Medline, Google Scholar
63 Purevdorj B, Costerton JW, Stoodley P. Influence of hydrodynamics and cell signaling on the structure and behavior of Pseudomonas aeruginosa biofilms. Appl. Environ. Microbiol.68(9),4457–4464 (2002).Crossref, Medline, CAS, Google Scholar
64 Reimmann C, Ginet N, Michel L et al. Genetically programmed autoinducer destruction reduces virulence gene expression and swarming motility in Pseudomonas aeruginosa PAO1. Microbiology148(Pt 4),923–932 (2002).Crossref, Medline, CAS, Google Scholar
65 Klausen M, Heydorn A, Ragas P et al. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol. Microbiol.48(6),1511–1524 (2003).Crossref, Medline, CAS, Google Scholar
66 O’Toole GA, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol.30(2),295–304 (1998).Crossref, Medline, Google Scholar
67 Flemming HC, Wingender J. The biofilm matrix. Nat. Rev. Microbiol.8(9),623–633 (2010).Crossref, Medline, CAS, Google Scholar
68 Allesen -Holm M, Barken KB, Yang L et al. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol. Microbiol.59(4),1114–1128 (2006).Crossref, Medline, Google Scholar
69 Yang L, Barken KB, Skindersoe ME, Christensen AB, Givskov M, Tolker-Nielsen T. Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa. Microbiology153(Pt 5),1318–1328 (2007).Crossref, Medline, CAS, Google Scholar
70 Yang L, Nilsson M, Gjermansen M, Givskov M, Tolker-Nielsen T. Pyoverdine and PQS mediated subpopulation interactions involved in Pseudomonas aeruginosa biofilm formation. Mol. Microbiol.74(6),1380–1392 (2009).Crossref, Medline, CAS, Google Scholar
71 Walker TS, Tomlin KL, Worthen GS et al. Enhanced Pseudomonas aeruginosa biofilm development mediated by human neutrophils. Infect. Immun.73(6),3693–3701 (2005).Crossref, Medline, CAS, Google Scholar
72 Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science280(5361),295–298 (1998).Crossref, Medline, CAS, Google Scholar
73 Heydorn A, Ersboll B, Kato J et al. Statistical analysis of Pseudomonas aeruginosa biofilm development: impact of mutations in genes involved in twitching motility, cell-to-cell signaling, and stationary-phase σ factor expression. Appl. Environ. Microbiol.68(4),2008–2017 (2002).Crossref, Medline, CAS, Google Scholar
74 Bjarnsholt T, Jensen PO, Burmolle M et al. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology151(Pt 2),373–383 (2005).Crossref, Medline, CAS, Google Scholar
75 Kirisits MJ, Margolis JJ, Purevdorj-Gage BL et al. Influence of the hydrodynamic environment on quorum sensing in Pseudomonas aeruginosa biofilms. J. Bacteriol.189(22),8357–8360 (2007).Crossref, Medline, CAS, Google Scholar
76 Stoodley P, Jacobsen A, Dunsmore BC et al. The influence of fluid shear and AICI3 on the material properties of Pseudomonas aeruginosa PAO1 and Desulfovibrio sp. EX265 biofilms. Water Sci. Technol.43(6),113–120 (2001).Crossref, Medline, CAS, Google Scholar
77 Kirisits MJ, Parsek MR. Does Pseudomonas aeruginosa use intercellular signalling to build biofilm communities? Cell Microbiol.8(12),1841–1849 (2006).Crossref, Medline, CAS, Google Scholar
78 Shrout JD, Chopp DL, Just CL, Hentzer M, Givskov M, Parsek MR. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol. Microbiol.62(5),1264–1277 (2006).Crossref, Medline, CAS, Google Scholar
79 Bollinger N, Hassett DJ, Iglewski BH, Costerton JW, McDermott TR. Gene expression in Pseudomonas aeruginosa: evidence of iron override effects on quorum sensing and biofilm-specific gene regulation. J. Bacteriol.183(6),1990–1996 (2001).Crossref, Medline, CAS, Google Scholar
80 Whiteley M, Bangera MG, Bumgarner RE et al. Gene expression in Pseudomonas aeruginosa biofilms. Nature413(6858),860–864 (2001).Crossref, Medline, CAS, Google Scholar
81 De Kievit TR, Gillis R, Marx S, Brown C, Iglewski BH. Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl. Environ. Microbiol.67(4),1865–1873 (2001).Crossref, Medline, Google Scholar
82 Folsom JP, Richards L, Pitts B et al. Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis. BMC Microbiol.10,294 (2010).Crossref, Medline, Google Scholar
83 Lequette Y, Greenberg EP. Timing and localization of rhamnolipid synthesis gene expression in Pseudomonas aeruginosa biofilms. J. Bacteriol.187(1),37–44 (2005).Crossref, Medline, CAS, Google Scholar
84 Davey ME, Caiazza NC, O’Toole GA. Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J. Bacteriol.185(3),1027–1036 (2003).Crossref, Medline, CAS, Google Scholar
85 Sakuragi Y, Kolter R. Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa. J. Bacteriol.189(14),5383–5386 (2007).Crossref, Medline, CAS, Google Scholar
86 Ueda A, Wood TK. Connecting quorum sensing, c-di-GMP, pel polysaccharide, and biofilm formation in Pseudomonas aeruginosa through tyrosine phosphatase TpbA (PA3885). PLoS Pathog.5(6),e1000483 (2009).Crossref, Medline, Google Scholar
87 Bjarnsholt T, Jensen PO, Fiandaca MJ et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol.44(6),547–558 (2009).Crossref, Medline, Google Scholar
88 Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am. J. Surg.187(5A),38S–43S (2004).Crossref, Medline, Google Scholar
89 Bjarnsholt T, Kirketerp-Moller K, Jensen PO et al. Why chronic wounds will not heal: a novel hypothesis. Wound Repair. Regen.16(1),2–10 (2008).Crossref, Medline, Google Scholar
90 Fazli M, Bjarnsholt T, Kirketerp-Moller K et al. Nonrandom distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds. J. Clin. Microbiol.47(12),4084–4089 (2009).Crossref, Medline, Google Scholar
91 James GA, Swogger E, Wolcott R et al. Biofilms in chronic wounds. Wound Repair. Regen.16(1),37–44 (2008).Crossref, Medline, Google Scholar
92 Kirketerp-Moller K, Jensen PO, Fazli M et al. Distribution, organization, and ecology of bacteria in chronic wounds. J. Clin. Microbiol.46(8),2717–2722 (2008).Crossref, Medline, Google Scholar
93 Gjodsbol K, Christensen JJ, Karlsmark T, Jorgensen B, Klein BM, Krogfelt KA. Multiple bacterial species reside in chronic wounds: a longitudinal study. Int. Wound J.3(3),225–231 (2006).Crossref, Medline, Google Scholar
94 Halbert AR, Stacey MC, Rohr JB, Jopp-McKay A. The effect of bacterial colonization on venous ulcer healing. Aus. J. Dermatol.33(2),75–80 (1992).Crossref, Medline, CAS, Google Scholar
95 Madsen SM, Westh H, Danielsen L, Rosdahl VT. Bacterial colonization and healing of venous leg ulcers. APMIS104(12),895–899 (1996).Crossref, Medline, CAS, Google Scholar
96 Hogsberg T, Bjarnsholt T, Thomsen JS, Kirketerp-Moller K. Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study. PLoS ONE6(5),e20492 (2011).Crossref, Medline, Google Scholar
97 Hall-Stoodley L, Stoodley P, Kathju S et al. Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol. Med. Microbiol.65(2),127–145 (2012).Crossref, Medline, CAS, Google Scholar
98 Jensen PO, Givskov M, Bjarnsholt T, Moser C. The immune system vs. Pseudomonas aeruginosa biofilms. FEMS Immunol. Med. Microbiol.59(3),292–305 (2010).Crossref, Medline, CAS, Google Scholar
99 Mah TF, O’Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol.9(1),34–39 (2001).Crossref, Medline, CAS, Google Scholar
100 Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev.15(2),167–193 (2002).Crossref, Medline, CAS, Google Scholar
101 Mah TF, Pitts B, Pellock B, Walker GC, Stewart PS, O’Toole GA. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature426(6964),306–310 (2003).Crossref, Medline, CAS, Google Scholar
102 Lewis K. Persister cells and the riddle of biofilm survival. Biochemistry (Mosc.)70(2),267–274 (2005).Crossref, Medline, CAS, Google Scholar
103 del Pozo JL, Patel R. The challenge of treating biofilm-associated bacterial infections. Clin. Pharmacol. Ther.82(2),204–209 (2007).Crossref, Medline, CAS, Google Scholar
104 Anderson GG, O’Toole GA. Innate and induced resistance mechanisms of bacterial biofilms. Curr. Topics Microbiol. Immunol.322,85–105 (2008).Crossref, Medline, CAS, Google Scholar
105 Haussler S, Ziegler I, Lottel A et al. Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. J. Med. Microbiol.52(Pt 4),295–301 (2003).Crossref, Medline, Google Scholar
106 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).Crossref, Medline, CAS, Google Scholar
107 Ramphal R, Lhermitte M, Filliat M, Roussel P. The binding of anti-pseudomonal antibiotics to macromolecules from cystic fibrosis sputum. J. Antimicrob. Chemother.22(4),483–490 (1988).Crossref, Medline, CAS, Google Scholar
108 Hunt BE, Weber A, Berger A, Ramsey B, Smith AL. Macromolecular mechanisms of sputum inhibition of tobramycin activity. Antimicrob. Agents Chemother.39(1),34–39 (1995).Crossref, Medline, CAS, Google Scholar
109 Purdy Drew KR, Sanders LK, Culumber ZW, Zribi O, Wong GC. Cationic amphiphiles increase activity of aminoglycoside antibiotic tobramycin in the presence of airway polyelectrolytes. J. Am. Chem. Soc.131(2),486–493 (2009).Crossref, Medline, Google Scholar
110 Mulcahy H, Charron-Mazenod L, Lewenza S. Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog.4(11),e1000213 (2008).Crossref, Medline, Google Scholar
111 Chiang WC, Nilsson M, Jensen PO et al. Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother.57(5),2352–2361 (2013).Crossref, Medline, CAS, Google Scholar
112 Nichols WW, Dorrington SM, Slack MP, Walmsley HL. Inhibition of tobramycin diffusion by binding to alginate. Antimicrob. Agents Chemother.32(4),518–523 (1988).Crossref, Medline, CAS, Google Scholar
113 Bagge N, Schuster M, Hentzer M et al. Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and β-lactamase and alginate production. Antimicrob. Agents Chemother.48(4),1175–1187 (2004).Crossref, Medline, CAS, Google Scholar
114 Smith EE, Buckley DG, Wu Z et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl Acad. Sci. USA103(22),8487–8492 (2006).Crossref, Medline, CAS, Google Scholar
115 Kolpen M, Hansen CR, Bjarnsholt T et al. Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis. Thorax65(1),57–62 (2010).Crossref, Medline, CAS, Google Scholar
116 Christensen LD, Moser C, Jensen PO et al. Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model. Microbiology153(Pt 7),2312–2320 (2007).Crossref, Medline, CAS, Google Scholar
117 Xiao G, Deziel E, He J et al. MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands. Mol. Microbiol.62(6),1689–1699 (2006).Crossref, Medline, CAS, Google Scholar
118 Alhede M, Bjarnsholt T, Jensen PO et al. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes. Microbiology155(Pt 11),3500–3508 (2009).Crossref, Medline, CAS, Google Scholar
119 Galloway WR, Hodgkinson JT, Bowden S, Welch M, Spring DR. Applications of small molecule activators and inhibitors of quorum sensing in Gram-negative bacteria. Trends Microbiol.20(9),449–458 (2012).Crossref, Medline, CAS, Google Scholar
120 Hentzer M, Riedel K, Rasmussen TB et al. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology148(Pt 1),87–102 (2002).Crossref, Medline, CAS, Google Scholar
121 Garde C, Bjarnsholt T, Givskov M et al. Quorum sensing regulation in Aeromonas hydrophila. J. Mol. Biol.396(4),849–857 (2010).Crossref, Medline, CAS, Google Scholar
122 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(5),1799–1814 (2005).Crossref, Medline, CAS, Google Scholar
123 Bjarnsholt T, van Gennip M, Jakobsen TH, Christensen LD, Jensen PO, Givskov M. In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect. Nat. Protoc.5(2),282–293 (2010).Crossref, Medline, CAS, Google Scholar
124 McClean KH, Winson MK, Fish L et al. Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology143(Pt 12),3703–3711 (1997).Crossref, Medline, CAS, Google Scholar
125 Shaw PD, Ping G, Daly SL et al. Detecting and characterizing N-acyl-homoserine lactone signal molecules by thin-layer chromatography. Proc. Natl Acad. Sci. USA94(12),6036–6041 (1997).Crossref, Medline, CAS, Google Scholar
126 Steindler L, Venturi V. Detection of quorum-sensing N-acyl homoserine lactone signal molecules by bacterial biosensors. FEMS Microbiol. Lett.266(1),1–9 (2007).Crossref, Medline, CAS, Google Scholar
127 Massai F, Imperi F, Quattrucci S, Zennaro E, Visca P, Leoni L. A multitask biosensor for micro-volumetric detection of N-3-oxo-dodecanoyl-homoserine lactone quorum sensing signal. Biosens. Bioelectron.26(8),3444–3449 (2011).Crossref, Medline, CAS, Google Scholar
128 Ortori CA, Atkinson S, Chhabra SR, Camara M, Williams P, Barrett DA. Comprehensive profiling of N-acylhomoserine lactones produced by Yersinia pseudotuberculosis using liquid chromatography coupled to hybrid quadrupole-linear ion trap mass spectrometry. Anal. Bioanal. Chem.387(2),497–511 (2007).Crossref, Medline, CAS, Google Scholar
129 Fletcher MP, Diggle SP, Crusz SA, Chhabra SR, Camara M, Williams P. A dual biosensor for 2-alkyl-4-quinolone quorum-sensing signal molecules. Environ. Microbiol.9(11),2683–2693 (2007).Crossref, Medline, CAS, Google Scholar
130 Fletcher MP, Diggle SP, Camara M, Williams P. Biosensor-based assays for PQS, HHQ and related 2-alkyl-4-quinolone quorum sensing signal molecules. Nat. Protoc.2(5),1254–1262 (2007).Crossref, Medline, CAS, Google Scholar
131 Diggle SP, Fletcher MP, Camara M, Williams P. Detection of 2-alkyl-4-quinolones using biosensors. Methods Mol. Biol.692,21–30 (2011).Crossref, Medline, CAS, Google Scholar
132 Yuan Y, Sachdeva M, Leeds JA, Meredith TC. Fatty acid biosynthesis in Pseudomonas aeruginosa is initiated by the FabY class of β-ketoacyl acyl carrier protein synthases. J. Bacteriol.194(19),5171–5184 (2012).Crossref, Medline, CAS, Google Scholar
133 Givskov M, de Nys R, Manefield M et al. Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J. Bacteriol.178(22),6618–6622 (1996).Crossref, Medline, CAS, Google Scholar
134 Wu H, Song Z, Hentzer M et al. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J. Antimicrob. Chemother.53(6),1054–1061 (2004).Crossref, Medline, CAS, Google Scholar
135 Rasmussen TB, Skindersoe ME, Bjarnsholt T et al. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology151(Pt 5),1325–1340 (2005).Crossref, Medline, CAS, Google Scholar
136 LaLonde RT, Bu L, Henwood A, Fiumano J, Zhang L. Bromine-, chlorine-, and mixed halogen-substituted 4-methyl-2(5H)-furanones: synthesis and mutagenic effects of halogen and hydroxyl group replacements. Chem. Res. Toxicol.10(12),1427–1436 (1997).Crossref, Medline, CAS, Google Scholar
137 Janecki T, Blaszczyk E, Studzian K, Rozalski M, Krajewska U, Janecka A. New stereocontrolled synthesis and biological evaluation of 5-(1’-hydroxyalkyl)-3-methylidenetetrahydro-2-furanones as potential cytotoxic agents. J. Med. Chem.45(5),1142–1145 (2002).Crossref, Medline, CAS, Google Scholar
138 Kim Y, Nam NH, You YJ, Ahn BZ. Synthesis and cytotoxicity of 3,4-diaryl-2(5H)-furanones. Bioorg. Med. Chem. Lett.12(4),719–722 (2002).Crossref, Medline, CAS, Google Scholar
139 Skindersoe ME, Ettinger-Epstein P, Rasmussen TB, Bjarnsholt T, de Nys R, Givskov M. Quorum sensing antagonism from marine organisms. Mar. Biotechnol. (NY)10(1),56–63 (2008).Crossref, Medline, CAS, Google Scholar
140 Bjarnsholt T, Jensen PO, Rasmussen TB et al. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology151(Pt 12),3873–3880 (2005).Crossref, Medline, CAS, Google Scholar
141 Jakobsen TH, van Gennip M, Phipps RK et al. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antimicrob. Agents Chemother.56(5),2314–2325 (2012).Crossref, Medline, CAS, Google Scholar
142 Jakobsen TH, Bragason SK, Phipps RK et al. Food as a source for quorum sensing inhibitors: iberin from horseradish revealed as a quorum sensing inhibitor of Pseudomonas aeruginosa. Appl. Environ. Microbiol.78(7),2410–2421 (2012).▪▪ Most comprehensive study of a QSI in relation to documenting activity both in vitro and in vivo.Crossref, Medline, CAS, Google Scholar
143 Ganin H, Rayo J, Amara N, Levy N, Krief P, Meijler MM. Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit, bacterial quorum sensing. Med. Chem. Commun.4,175–179 (2013).Crossref, CAS, Google Scholar
144 Amara N, Mashiach R, Amar D et al. Covalent inhibition of bacterial quorum sensing. J. Am. Chem. Soc.131(30),10610–10619 (2009).Crossref, Medline, CAS, Google Scholar
145 Christensen LD, van Gennip M, Jakobsen TH et al. Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model. J. Antimicrob. Chemother.67(5),1198–1206 (2012).Crossref, Medline, CAS, Google Scholar
146 Brackman G, Cos P, Maes L, Nelis HJ, Coenye T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob. Agents Chemother.55(6),2655–2661 (2011).Crossref, Medline, CAS, Google Scholar
147 Smyth AR, Cifelli PM, Ortori CA et al. Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis – a pilot randomized controlled trial. Pediatr. Pulmonol.45(4),356–362 (2010).Crossref, Medline, Google Scholar
148 Geske GD, O’Neill JC, Blackwell HE. Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria. Chem. Soc. Rev.37(7),1432–1447 (2008).▪ Very thorough review of the different identified QSIs.Crossref, Medline, CAS, Google Scholar
149 Galloway WR, Hodgkinson JT, Bowden SD, Welch M, Spring DR. Quorum sensing in Gram-negative bacteria: small-molecule modulation of AHL and AI-2 quorum sensing pathways. Chem. Rev.111(1),28–67 (2011).▪▪ Most comprehensive structure-based analysis of QSIs.Crossref, Medline, CAS, Google Scholar
150 Bottomley MJ, Muraglia E, Bazzo R, Carfi A. Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. J. Biol. Chem.282(18),13592–13600 (2007).Crossref, Medline, CAS, Google Scholar
151 Yang L, Rybtke MT, Jakobsen TH et al. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. Antimicrob. Agents Chemother.53(6),2432–2443 (2009).Crossref, Medline, CAS, Google Scholar
152 Skovstrup S, Le Quement ST, Hansen T et al. Identification of LasR ligands through a virtual screening approach. ChemMedChem8(1),157–163 (2013).Crossref, Medline, CAS, Google Scholar
153 Annapoorani A, Umamageswaran V, Parameswari R, Pandian SK, Ravi AV. Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa. J. Comput. Aided Mol. Des.26(9),1067–1077 (2012).Crossref, Medline, CAS, Google Scholar
154 Muh U, Schuster M, Heim R, Singh A, Olson ER, Greenberg EP. Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen. Antimicrob. Agents Chemother.50(11),3674–3679 (2006).Crossref, Medline, CAS, Google Scholar
155 Skindersoe ME, Alhede M, Phipps R et al. Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.52(10),3648–3663 (2008).Crossref, Medline, CAS, Google Scholar
156 Perez-Martinez I, Haas D. Azithromycin inhibits expression of the GacA-dependent small RNAs RsmY and RsmZ in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.55(7),3399–3405 (2011).Crossref, Medline, CAS, Google Scholar
157 Hoffmann N, Lee B, Hentzer M et al. 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(10),3677–3687 (2007).Crossref, Medline, CAS, Google Scholar
158 Bala A, Kumar R, Harjai K. Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections. J. Med. Microbiol.60(Pt 3),300–306 (2011).Crossref, Medline, CAS, Google Scholar
159 Kohler T, Guanella R, Carlet J, van Delden C. Quorum sensing-dependent virulence during Pseudomonas aeruginosa colonisation and pneumonia in mechanically ventilated patients. Thorax65(8),703–710 (2010).▪ Important investigation showing the use of the QSI azithromycin against ventilator-associated pneumonia.Crossref, Medline, Google Scholar
160 van Delden C, Kohler T, Brunner-Ferber F, Francois B, Carlet J, Pechere JC. Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial. Intensive Care Med.38(7),1118–1125 (2012).Crossref, Medline, Google Scholar
161 Imperi F, Massai F, Ramachandran Pillai C et al. New life for an old drug: the anthelmintic drug niclosamide inhibits Pseudomonas aeruginosa quorum sensing. Antimicrob. Agents Chemother.57(2),996–1005 (2013).Crossref, Medline, CAS, Google Scholar
162 Calfee MW, Coleman JP, Pesci EC. Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA98(20),11633–11637 (2001).Crossref, Medline, CAS, Google Scholar
163 Lesic B, Lepine F, Deziel E et al. Inhibitors of pathogen intercellular signals as selective anti-infective compounds. PLoS Pathog.3(9),1229–1239 (2007).Crossref, Medline, CAS, Google Scholar
164 Klein T, Henn C, de Jong JC et al. Identification of small-molecule antagonists of the Pseudomonas aeruginosa transcriptional regulator PqsR: biophysically guided hit discovery and optimization. ACS Chem. Biol.7(9),1496–1501 (2012).Crossref, Medline, CAS, Google Scholar
165 Zaborina O, Lepine F, Xiao G et al. Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog.3(3),e35 (2007).Crossref, Medline, Google Scholar
166 Storz MP, Maurer CK, Zimmer C et al. Validation of PqsD as an anti-biofilm target in Pseudomonas aeruginosa by development of small-molecule inhibitors. J. Am. Chem. Soc.134(39),16143–16146 (2012).Crossref, Medline, CAS, Google Scholar
167 Lewis K. Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol.5(1),48–56 (2007).Crossref, Medline, CAS, Google Scholar
168 Fux CA, Stoodley P, Hall-Stoodley L, Costerton JW. Bacterial biofilms: a diagnostic and therapeutic challenge. Expert Rev. Anti. Infect. Ther.1(4),667–683 (2003).Crossref, Medline, Google Scholar
169 Maeda T, Garcia-Contreras R, Pu M et al. Quorum quenching quandary: resistance to antivirulence compounds. ISME J.6(3),493–501 (2012).Crossref, Medline, CAS, Google Scholar
170 Chen H, Yi C, Zhang J et al. Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR. EMBO Rep.11(9),685–690 (2010).Crossref, Medline, CAS, Google Scholar
171 Pearson JP, Van Delden C, Iglewski BH. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals. J. Bacteriol.181(4),1203–1210 (1999).Crossref, Medline, CAS, Google Scholar
172 Mellbye B, Schuster M. The sociomicrobiology of antivirulence drug resistance: a proof of concept. MBio2(5),e00131-11 (2011).▪ Important investigation showing that a QSI-resistant subpopulation in a culture is unlikely to spread to the entire culture.Crossref, Medline, Google Scholar
173 Ciofu O, Mandsberg LF, Bjarnsholt T, Wassermann T, Hoiby N. 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. Microbiology156(Pt 4),1108–1119 (2010).Crossref, Medline, CAS, Google Scholar
174 Folkesson A, Jelsbak L, Yang L et al. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat. Rev. Microbiol.10(12),841–851 (2012).Crossref, Medline, CAS, Google Scholar
175 Bjarnsholt T, Jensen PO, Jakobsen TH et al. Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS ONE5(4),e10115 (2010).Crossref, Medline, Google Scholar
176 Bielecki P, Komor U, Bielecka A et al. Ex vivo transcriptional profiling reveals a common set of genes important for the adaptation of Pseudomonas aeruginosa to chronically infected host sites. Environ. Microbiol.15(2),570–587 (2013).Crossref, Medline, CAS, Google Scholar
177 D’Argenio DA, Wu M, Hoffman LR et al. Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol. Microbiol.64(2),512–533 (2007).Crossref, Medline, Google Scholar
178 Heurlier K, Denervaud V, Haas D. Impact of quorum sensing on fitness of Pseudomonas aeruginosa. Int J. Med. Microbiol.296(2–3),93–102 (2006).Crossref, Medline, CAS, Google Scholar
179 Schaber JA, Carty NL, McDonald NA et al. Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa. J. Med. Microbiol.53(Pt 9),841–853 (2004).Crossref, Medline, CAS, Google Scholar
180 Erickson DL, Endersby R, Kirkham A et al. Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect. Immun.70(4),1783–1790 (2002).Crossref, Medline, CAS, Google Scholar
181 Middleton B, Rodgers HC, Camara M, Knox AJ, Williams P, Hardman A. Direct detection of N-acylhomoserine lactones in cystic fibrosis sputum. FEMS Microbiol. Lett.207(1),1–7 (2002).Crossref, Medline, CAS, Google Scholar
182 Chambers CE, Visser MB, Schwab U, Sokol PA. Identification of N-acylhomoserine lactones in mucopurulent respiratory secretions from cystic fibrosis patients. FEMS Microbiol. Lett.244(2),297–304 (2005).Crossref, Medline, CAS, Google Scholar
183 Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature407(6805),762–764 (2000).▪ First investigation showing the presence of QS signal molecules in sputum samples from cystic fibrosis patients infected with Pseudomonas aeruginosa.Crossref, Medline, CAS, Google Scholar
184 Wilder CN, Allada G, Schuster M. Instantaneous within-patient diversity of Pseudomonas aeruginosa quorum-sensing populations from cystic fibrosis lung infections. Infect. Immun.77(12),5631–5639 (2009).Crossref, Medline, CAS, Google Scholar
185 Diggle SP, Griffin AS, Campbell GS, West SA. Cooperation and conflict in quorum-sensing bacterial populations. Nature450(7168),411–414 (2007).▪ Investigation showing the social evolution of QS in a P. aeruginosa culture.Crossref, Medline, CAS, Google Scholar
186 Kohler T, Buckling A, van Delden C. Cooperation and virulence of clinical Pseudomonas aeruginosa populations. Proc. Natl Acad. Sci. USA106(15),6339–6344 (2009).▪ Investigation determining the social evolution of QS in vivo. The percentage of QS cheaters (lasR mutants) increases during infection periods, leading to diverse cultures.Crossref, Medline, CAS, Google Scholar
187 Kohler T, Perron GG, Buckling A, van Delden C. Quorum sensing inhibition selects for virulence and cooperation in Pseudomonas aeruginosa. PLoS Pathog.6(5),e1000883 (2010).Crossref, Medline, Google Scholar
188 Musken M, Di Fiore S, Romling U, Haussler S. A 96-well-plate-based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application to susceptibility testing. Nat. Protoc.5(8),1460–1469 (2010).Crossref, Medline, Google Scholar
201 Kumar N, Read R. Production of furanones. EP1787988 A3 (2007).Google Scholar

Vol. 8, No. 7

Metrics

Downloaded 925 times

History

Published online 10 July 2013

Published in print July 2013

Information

Keywords

Financial & competing interests disclosure

Work on quorum sensing and quorum sensing inhibition has over the years been supported by two grants from the Danish Strategical Research Council, the German CF organization, the Villum foundation and Novoseeds to M Givskov and the Lundbeckfonden to T Bjarnsholt. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download