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PMID: 14597754 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections.

The Journal of clinical investigation ·Vol. 112 ·No. 9 ·2003-11-00 ·Pages 1300-7

Hentzer M, Givskov M

Abstract

Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum-sensing systems), which orchestrate important temporal events during the infection process, has afforded a novel opportunity to ameliorate bacterial infection by means other than growth inhibition. Compounds able to override bacterial signaling are present in nature. Herein we discuss the known signaling mechanisms and potential antipathogenic drugs that specifically target quorum-sensing systems in a manner unlikely to pose a selective pressure for the development of resistant mutants.

MeSH Terms
4-Butyrolactone/analogs & derivatives,antagonists & inhibitors,physiology Animals Anti-Bacterial Agents/pharmacology Bacterial Infections/drug therapy Biofilms Chronic Disease Furans/pharmacology Humans Signal Transduction/drug effects
Chemicals
Anti-Bacterial Agents Furans homoserine lactone 4-Butyrolactone
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hentzer Morten
Center for Biomedical Microbiology, BioCentrum, Building 301, Technical University of Denmark, DK-2800 Lyngby, Denmark. [email protected]
Givskov Michael
References (53)
53 references, click to expand
  1. The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility.
    Microbiology. 2001 Sep;147(Pt 9):2517-28 PMID: 11535791
  2. LuxS quorum sensing: more than just a numbers game.
    Curr Opin Microbiol. 2003 Apr;6(2):191-7 PMID: 12732311
  3. Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein.
    Microbiology. 1999 Feb;145 ( Pt 2):283-91 PMID: 10075410
  4. Biofilm resistance to antimicrobial agents.
    Microbiology. 2000 Mar;146 ( Pt 3):547-9 PMID: 10746758
  5. Quorum sensing: potential means of treating gram-negative infections?
    Lancet. 1998 Mar 21;351(9106):848-9 PMID: 9525356
  6. Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants.
    J Bacteriol. 2002 Dec;184(23):6481-9 PMID: 12426335
  7. N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa.
    Infect Immun. 2002 Oct;70(10):5635-46 PMID: 12228292
  8. AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3526-31 PMID: 10716724
  9. Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa.
    Antimicrob Agents Chemother. 2001 Jun;45(6):1930-3 PMID: 11353657
  10. Acyl homoserine-lactone quorum-sensing signal generation.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4360-5 PMID: 10200267
  11. Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria.
    Mol Plant Microbe Interact. 2000 Jun;13(6):637-48 PMID: 10830263
  12. Bacterial biofilms: a common cause of persistent infections.
    Science. 1999 May 21;284(5418):1318-22 PMID: 10334980
  13. Functional analysis of the Pseudomonas aeruginosa autoinducer PAI.
    J Bacteriol. 1996 Oct;178(20):5995-6000 PMID: 8830697
  14. N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms.
    Microbiology. 2001 Dec;147(Pt 12):3249-62 PMID: 11739757
  15. Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication.
    Science. 1993 May 21;260(5111):1127-30 PMID: 8493556
  16. The involvement of cell-to-cell signals in the development of a bacterial biofilm.
    Science. 1998 Apr 10;280(5361):295-8 PMID: 9535661
  17. Quorum sensing in Burkholderia cepacia: identification of the LuxRI homologs CepRI.
    J Bacteriol. 1999 Feb;181(3):748-56 PMID: 9922236
  18. Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs.
    Chem Biol. 2003 Jan;10(1):81-9 PMID: 12573701
  19. Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa.
    J Bacteriol. 2002 Dec;184(23):6472-80 PMID: 12426334
  20. New pharmaceuticals from marine organisms.
    Trends Biotechnol. 1997 Sep;15(9):339-41 PMID: 9293031
  21. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors.
    EMBO J. 2003 Aug 1;22(15):3803-15 PMID: 12881415
  22. Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1.
    Mol Microbiol. 1995 Jul;17(2):333-43 PMID: 7494482
  23. Bacterial biofilms in nature and disease.
    Annu Rev Microbiol. 1987;41:435-64 PMID: 3318676
  24. Expression of a luxS gene is not required for Borrelia burgdorferi infection of mice via needle inoculation.
    Infect Immun. 2003 May;71(5):2892-6 PMID: 12704164
  25. Impact of CLOD Pathogen on Pacific Coral Reefs.
    Science. 1995 Mar 3;267(5202):1356-60 PMID: 17812612
  26. Bacterial signals and antagonists: the interaction between bacteria and higher organisms.
    J Mol Microbiol Biotechnol. 1999 Aug;1(1):23-31 PMID: 10941781
  27. Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones.
    Microbiology. 1997 Dec;143 ( Pt 12):3703-11 PMID: 9421896
  28. Riddle of biofilm resistance.
    Antimicrob Agents Chemother. 2001 Apr;45(4):999-1007 PMID: 11257008
  29. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound.
    Microbiology. 2002 Jan;148(Pt 1):87-102 PMID: 11782502
  30. N-acyl homoserinelactone-mediated gene regulation in gram-negative bacteria.
    Syst Appl Microbiol. 1999 Dec;22(4):493-506 PMID: 10794136
  31. Autoregulation of carbapenem biosynthesis in Erwinia carotovora by analogues of N-(3-oxohexanoyl)-L-homoserine lactone.
    J Antibiot (Tokyo). 1993 Mar;46(3):441-54 PMID: 8478262
  32. Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists.
    Appl Environ Microbiol. 2000 May;66(5):2079-84 PMID: 10788385
  33. Production of acyl-homoserine lactone quorum-sensing signals by gram-negative plant-associated bacteria.
    Mol Plant Microbe Interact. 1998 Nov;11(11):1119-29 PMID: 9805399
  34. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria.
    Clin Infect Dis. 1998 Aug;27 Suppl 1:S93-9 PMID: 9710677
  35. Azithromycin reduces the production of virulence factors in Pseudomonas aeruginosa by inhibiting quorum sensing.
    Jpn J Antibiot. 2001 Dec;54 Suppl C:87-9 PMID: 12575427
  36. How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1.
    Microbiology. 2000 Dec;146 Pt 12:3237-44 PMID: 11101681
  37. LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.
    Microbiology. 2002 Apr;148(Pt 4):909-22 PMID: 11932438
  38. 'Subinhibitory' erythromycin represses production of Pseudomonas aeruginosa lectins, autoinducer and virulence factors.
    Chemotherapy. 1999 Sep-Oct;45(5):335-41 PMID: 10473921
  39. Quorum sensing-dependent regulation and blockade of exoprotease production in Aeromonas hydrophila.
    Infect Immun. 1999 Oct;67(10):5192-9 PMID: 10496895
  40. Metabolism of acyl-homoserine lactone quorum-sensing signals by Variovorax paradoxus.
    J Bacteriol. 2000 Dec;182(24):6921-6 PMID: 11092851
  41. Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa.
    Microbiology. 2000 Oct;146 ( Pt 10):2481-93 PMID: 11021924
  42. Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase.
    Nature. 2001 Jun 14;411(6839):813-7 PMID: 11459062
  43. Quorum sensing in Aeromonas hydrophila and Aeromonas salmonicida: identification of the LuxRI homologs AhyRI and AsaRI and their cognate N-acylhomoserine lactone signal molecules.
    J Bacteriol. 1997 Sep;179(17):5271-81 PMID: 9286976
  44. Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling.
    J Bacteriol. 1996 Nov;178(22):6618-22 PMID: 8932319
  45. Halogenated furanones from the red alga, Delisea pulchra, inhibit carbapenem antibiotic synthesis and exoenzyme virulence factor production in the phytopathogen Erwinia carotovora.
    FEMS Microbiol Lett. 2001 Nov 27;205(1):131-8 PMID: 11728727
  46. Analogs of the autoinducer 3-oxooctanoyl-homoserine lactone strongly inhibit activity of the TraR protein of Agrobacterium tumefaciens.
    J Bacteriol. 1998 Oct;180(20):5398-405 PMID: 9765571
  47. Capsular polysaccharide biosynthesis and pathogenicity in Erwinia stewartii require induction by an N-acylhomoserine lactone autoinducer.
    J Bacteriol. 1995 Sep;177(17):5000-8 PMID: 7665477
  48. The regulation of biofilm development by quorum sensing in Aeromonas hydrophila.
    Environ Microbiol. 2002 Jan;4(1):18-28 PMID: 11966822
  49. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs.
    J Bacteriol. 1996 May;178(10):2897-901 PMID: 8631679
  50. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system.
    Mol Microbiol. 2003 Jun;48(6):1647-64 PMID: 12791145
  51. Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2771-6 PMID: 12601166
  52. Structural identification of a bacterial quorum-sensing signal containing boron.
    Nature. 2002 Jan 31;415(6871):545-9 PMID: 11823863
  53. Novel synthetic analogs of the Pseudomonas autoinducer.
    Bioorg Med Chem Lett. 1999 Dec 20;9(24):3447-52 PMID: 10617089
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI20074
Email
[email protected]
Published
2003-11-00
Pages
1300-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC228474
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI20074 PMC Full Text View journal details
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