1887

Abstract

Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In , QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host innate immune system. Therefore, QS is an obvious target for a novel class of antimicrobial drugs which would function to efficiently block reception of the cognate QS signals , and thereby be capable of inducing chemical attenuation of pathogens. As QS is not directly involved in processes essential for growth of the bacteria, inhibition of QS does not impose harsh selective pressure for development of resistance as with antibiotics. Numerous chemical libraries of both natural and synthetic origin have been screened and several QS-inhibitory compounds have been identified. In animal pulmonary infection models, such inhibitors have proven able to significantly improve clearing of the infecting bacteria and reduce mortality. In addition, several enzymes that are able to inactivate the bacterial QS signal molecules have been identified. This inactivation leads to blockage of QS-mediated virulence of plant pathogens in several models.

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2006-04-01
2024-03-28
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References

  1. Allison C, Lai H. C, Gygi D, Hughes C. 1993; Cell differentiation of Proteus mirabilis is initiated by glutamine, a specific chemoattractant for swarming cells. Mol Microbiol 8:53–60 [CrossRef]
    [Google Scholar]
  2. Anwar H, Dasgupta M. K, Costerton J. W. 1990; Testing the susceptibility of bacteria in biofilms to antibacterial agents. Antimicrob Agents Chemother 34:2043–2046 [CrossRef]
    [Google Scholar]
  3. Arevalo-Ferro C, Hentzer M, Reil G, Gorg A, Kjelleberg S, Givskov M, Riedel K, Eberl L. 2003; Identification of quorum-sensing regulated proteins in the opportunistic pathogen Pseudomonas aeruginosa by proteomics. Environ Microbiol 5:1350–1369 [CrossRef]
    [Google Scholar]
  4. Bjarnsholt T, Jensen P. O, Burmolle M. 9 other authors 2005a; Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151:373–383 [CrossRef]
    [Google Scholar]
  5. Bjarnsholt T, Jensen P. O, Rasmussen T. B. 9 other authors 2005b; Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 151:3873–3880 [CrossRef]
    [Google Scholar]
  6. Borchardt S. A, Allain E. J, Michels J. J, Stearns G. W, Kelly R. F, McCoy W. F. 2001; Reaction of acylated homoserine lactone bacterial signaling molecules with oxidized halogen antimicrobials. Appl Environ Microbiol 67:3174–3179 [CrossRef]
    [Google Scholar]
  7. Byers J. T, Lucas C, Salmond G. P, Welch M. 2002; Nonenzymatic turnover of an Erwinia carotovora quorum-sensing signaling molecule. J Bacteriol 184:1163–1171 [CrossRef]
    [Google Scholar]
  8. Camara M, Williams P, Hardman A. 2002; Controlling infection by tuning in and turning down the volume of bacterial small-talk. Lancet Infect Dis 2:667–676 [CrossRef]
    [Google Scholar]
  9. Campanac C, Pineau L, Payard A, Baziard-Mouysset G, Roques C. 2002; Interactions between biocide cationic agents and bacterial biofilms. Antimicrob Agents Chemother 46:1469–1474 [CrossRef]
    [Google Scholar]
  10. Carlier A, Uroz S, Smadja B, Fray R, Latour X, Dessaux Y, Faure D. 2003; The Ti plasmid of Agrobacterium tumefaciens harbors an attM -paralogous gene, aiiB , also encoding N -acyl homoserine lactonase activity. Appl Environ Microbiol 69:4989–4993 [CrossRef]
    [Google Scholar]
  11. Castang S, Chantegrel B, Deshayes C. 7 other authors 2004; N -Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing. Bioorg Med Chem Lett 14:5145–5149 [CrossRef]
    [Google Scholar]
  12. Chun C. K, Ozer E. A, Welsh M. J, Zabner J, Greenberg E. P. 2004; Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc Natl Acad Sci U S A 101:3587–3590 [CrossRef]
    [Google Scholar]
  13. Costerton J. W, Cheng K. J, Geesey G. G, Ladd T. I, Nickel J. C, Dasgupta M, Marrie T. J. 1987; Bacterial biofilms in nature and disease. Annu Rev Microbiol 41:435–464 [CrossRef]
    [Google Scholar]
  14. Costerton J. W, Stewart P. S, Greenberg E. P. 1999; Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322 [CrossRef]
    [Google Scholar]
  15. Davies D. 2003; Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2:114–122 [CrossRef]
    [Google Scholar]
  16. Davies D. G, Parsek M. R, Pearson J. P, Iglewski B. H, Costerton J. W, Greenberg E. P. 1998; The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280:295–298 [CrossRef]
    [Google Scholar]
  17. Diggle S. P, Winzer K, Chhabra S. R, Worrall K. E, Camara M, Williams P. 2003; 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 50:29–43 [CrossRef]
    [Google Scholar]
  18. Dong Y. H, Xu J. L, Li X. Z, Zhang L. H. 2000; 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 97:3526–3531 [CrossRef]
    [Google Scholar]
  19. Dong Y. H, Wang L. H, Xu J. L, Zhang H. B, Zhang X. F, Zhang L. H. 2001; Quenching quorum-sensing-dependent bacterial infection by an N -acyl homoserine lactonase. Nature 411:813–817 [CrossRef]
    [Google Scholar]
  20. Dong Y. H, Zhang X. F, Xu J. L, Zhang L. H. 2004; Insecticidal Bacillus thuringiensis silences Erwinia carotovora virulence by a new form of microbial antagonism, signal interference. Appl Environ Microbiol 70:954–960 [CrossRef]
    [Google Scholar]
  21. Drenkard E. 2003; Antimicrobial resistance of Pseudomonas aeruginosa biofilms. Microbes Infect 5:1213–1219 [CrossRef]
    [Google Scholar]
  22. Drenkard E, Ausubel F. M. 2002; Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416:740–743 [CrossRef]
    [Google Scholar]
  23. Eberl L. 1999; N -acyl homoserinelactone-mediated gene regulation in gram-negative bacteria. Syst Appl Microbiol 22:493–506 [CrossRef]
    [Google Scholar]
  24. Eberl L, Winson M. K, Sternberg C. 7 other authors 1996; Involvement of N -acyl-l-hormoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens . Mol Microbiol 20:127–136 [CrossRef]
    [Google Scholar]
  25. Engebrecht J, Silverman M. 1984; Identification of genes and gene products necessary for bacterial bioluminescence. Proc Natl Acad Sci U S A 81:4154–4158 [CrossRef]
    [Google Scholar]
  26. Fuqua W. C, Winans S. C, Greenberg E. P. 1994; Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176:269–275
    [Google Scholar]
  27. Gallagher L. A, McKnight S. L, Kuznetsova M. S, Pesci E. C, Manoil C. 2002; Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa . J Bacteriol 184:6472–6480 [CrossRef]
    [Google Scholar]
  28. 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
    [Google Scholar]
  29. Hastings J. W. 2004; Bacterial quorum-sensing signals are inactivated by mammalian cells. Proc Natl Acad Sci U S A 101:3993–3994 [CrossRef]
    [Google Scholar]
  30. Hentzer M, Riedel K, Rasmussen T. B. 9 other authors 2002; Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148:87–102
    [Google Scholar]
  31. Hentzer M, Eberl L, Givskov M. 2005; Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2:37–61 [CrossRef]
    [Google Scholar]
  32. Hentzer M, Wu H, Andersen J. B. 15 other authors 2003; Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815 [CrossRef]
    [Google Scholar]
  33. 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 [CrossRef]
    [Google Scholar]
  34. Hoiby N, Krogh J. H, Moser C, Song Z, Ciofu O, Kharazmi A. 2001; Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth. Microbes Infect 3:23–35 [CrossRef]
    [Google Scholar]
  35. 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 [CrossRef]
    [Google Scholar]
  36. Koch B, Liljefors T, Persson T, Nielsen J, Kjelleberg S, Givskov M. 2005; The LuxR receptor: the sites of interaction with quorum sensing signals and inhibitors. Microbiology 151:3589–3602 [CrossRef]
    [Google Scholar]
  37. Latifi A, Foglino M, Tanaka K, Williams P, Lazdunski A. 1996; A hierarchical quorum-sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationary-phase sigma factor RpoS. Mol Microbiol 21:1137–1146 [CrossRef]
    [Google Scholar]
  38. Leadbetter J. R, Greenberg E. P. 2000; Metabolism of acyl-homoserine lactone quorum-sensing signals by Variovorax paradoxus . J Bacteriol 182:6921–6926 [CrossRef]
    [Google Scholar]
  39. Lee S. J, Park S. Y, Lee J. J, Yum D. Y, Koo B. T, Lee J. K. 2002; Genes encoding the N -acyl homoserine lactone-degrading enzyme are widespread in many subspecies of Bacillus thuringiensis . Appl Environ Microbiol 68:3919–3924 [CrossRef]
    [Google Scholar]
  40. Lewis K. 2001; Riddle of biofilm resistance. Antimicrob Agents Chemother 45:999–1007 [CrossRef]
    [Google Scholar]
  41. Mah T. F, Pitts B, Pellock B, Walker G. C, Stewart P. S, O'Toole G. A. 2003; A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426:306–310 [CrossRef]
    [Google Scholar]
  42. Mahajan-Miklos S, Tan M. W, Rahme L. G, Ausubel F. M. 1999; Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa - Caenorhabditis elegans pathogenesis model. Cell 96:47–56 [CrossRef]
    [Google Scholar]
  43. Manefield M, Turner S. L. 2002; Quorum sensing in context: out of molecular biology and into microbial ecology. Microbiology 148:3762–3764
    [Google Scholar]
  44. 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
    [Google Scholar]
  45. Manny A. J, Kjelleberg S, Kumar N, de Nys R, Read R. W, Stainberg P. 1997; Reinvestigation of the sulfuric acid-catalysed cyclisation of brominated 2-alkyllevulinic acids to 3-alkyl-5-methylene-2(5H)-furanones. Tetrahedron 53:15813–15826 [CrossRef]
    [Google Scholar]
  46. Maximilien R, de Nys R, Holmstrom C, Gram L, Givskov M, Kjelleberg S, Steinberg P. 1998; Chemical mediation of bacterial surface colonisation by secondary metabolites from the red alga Delisea pulchra . Aquat Microb Ecol 15:233–246 [CrossRef]
    [Google Scholar]
  47. McKnight S. L, Iglewski B. H, Pesci E. C. 2000; The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa . J Bacteriol 182:2702–2708 [CrossRef]
    [Google Scholar]
  48. Molina L, Constantinescu F, Michel L, Reimmann C, Duffy B, Defago G. 2003; Degradation of pathogen quorum-sensing molecules by soil bacteria: a preventive and curative biological control mechanism. FEMS Microbiol Ecol 45:71–81 [CrossRef]
    [Google Scholar]
  49. Olsen J. A, Severinsen R, Rasmussen T. B, Hentzer M, Givskov M, Nielsen J. 2002; Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers. Bioorg Med Chem Lett 12:325–328 [CrossRef]
    [Google Scholar]
  50. Park S. Y, Lee S. J, Oh T. K, Oh J. W, Koo B. T, Yum D. Y, Lee J. K. 2003; AhlD, an N -acylhomoserine lactonase in Arthrobacter sp., and predicted homologues in other bacteria. Microbiology 149:1541–1550 [CrossRef]
    [Google Scholar]
  51. Parsek M. R, Val D. L, Hanzelka B. L, Cronan J. E, Greenberg E. P. 1999; Acyl homoserine-lactone quorum-sensing signal generation. Proc Natl Acad Sci U S A 96:4360–4365 [CrossRef]
    [Google Scholar]
  52. Passador L, Tucker K. D, Guertin K. R, Journet M. P, Kende A. S, Iglewski B. H. 1996; Functional analysis of the Pseudomonas aeruginosa autoinducer PAI. J Bacteriol 178:5995–6000
    [Google Scholar]
  53. Pedersen S. S, Shand G. H, Hansen B. L, Hansen G. N. 1990; Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres. APMIS 98:203–211 [CrossRef]
    [Google Scholar]
  54. Persson T, Hansen T. H, Rasmussen T. B, Skinderso M. E, Givskov M, Nielsen J. 2005; Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic. Org Biomol Chem 3:253–262 [CrossRef]
    [Google Scholar]
  55. Pesci E. C, Iglewski B. H. 1997; The chain of command in Pseudomonas quorum sensing. Trends Microbiol 5:132–134 [CrossRef]
    [Google Scholar]
  56. 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
    [Google Scholar]
  57. Pesci E. C, Milbank J. B, Pearson J. P, McKnight S, Kende A. S, Greenberg E. P, Iglewski B. H. 1999; Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa . Proc Natl Acad Sci U S A 96:11229–11234 [CrossRef]
    [Google Scholar]
  58. Rasmussen T. B, Manefield M, Andersen J. B, Eberl L, Anthoni U, Christophersen C, Steinberg P, Kjelleberg S, Givskov M. 2000; How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1. Microbiology 146:3237–3244
    [Google Scholar]
  59. Rasmussen T. B, Bjarnsholt T, Skindersoe M. E, Hentzer M, Kristoffersen P, Kote M, Nielsen J, Eberl L, Givskov M. 2005a; Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187:1799–1814 [CrossRef]
    [Google Scholar]
  60. Rasmussen T. B, Skindersoe M. E, Bjarnsholt T. 10 other authors 2005b; Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151:1325–1340 [CrossRef]
    [Google Scholar]
  61. Reverchon S, Chantegrel B, Deshayes C, Doutheau A, Cotte-Pattat N. 2002; New synthetic analogues of N -acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing. Bioorg Med Chem Lett 12:1153–1157 [CrossRef]
    [Google Scholar]
  62. Salmond G. P, Bycroft B. W, Stewart G. S, Williams P. 1995; The bacterial ‘enigma’: cracking the code of cell-cell communication. Mol Microbiol 16:615–624 [CrossRef]
    [Google Scholar]
  63. Schaefer A. L, Hanzelka B. L, Eberhard A, Greenberg E. P. 1996; Quorum sensing in Vibrio fischeri : probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol 178:2897–2901
    [Google Scholar]
  64. 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 [CrossRef]
    [Google Scholar]
  65. Schuster M, Urbanowski M. L, Greenberg E. P. 2004; Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA binding of purified LasR. Proc Natl Acad Sci U S A 101:15833–15839 [CrossRef]
    [Google Scholar]
  66. Seed P. C, Passador L, Iglewski B. H. 1995; Activation of the Pseudomonas aeruginosa lasI gene by LasR and the Pseudomonas autoinducer PAI: an autoinduction regulatory hierarchy. J Bacteriol 177:654–659
    [Google Scholar]
  67. Smith K. M, Bu Y, Suga H. 2003a; Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs. Chem Biol 10:81–89 [CrossRef]
    [Google Scholar]
  68. Smith K. M, Bu Y, Suga H. 2003b; Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer. Chem Biol 10:563–571 [CrossRef]
    [Google Scholar]
  69. Tan M. W, Mahajan-Miklos S, Ausubel F. M. 1999; Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A 96:715–720 [CrossRef]
    [Google Scholar]
  70. Teitzel G. M, Parsek M. R. 2003; Heavy metal resistance of biofilm and planktonic Pseudomonas aeruginosa . Appl Environ Microbiol 69:2313–2320 [CrossRef]
    [Google Scholar]
  71. Teplitski M, Robinson J. B, Bauer W. D. 2000; 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 13:637–648 [CrossRef]
    [Google Scholar]
  72. Uroz S, D'Angelo-Picard C, Carlier A, Elasri M, Sicot C, Petit A, Oger P, Faure D, Dessaux Y. 2003; Novel bacteria degrading N -acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria. Microbiology 149:1981–1989 [CrossRef]
    [Google Scholar]
  73. Van Delden C, Iglewski B. H. 1998; Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560 [CrossRef]
    [Google Scholar]
  74. 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 [CrossRef]
    [Google Scholar]
  75. Wang L. H, Weng L. X, Dong Y. H, Zhang L. H. 2004; Specificity and enzyme kinetics of the quorum-quenching N -acyl homoserine lactone lactonase (AHL-lactonase). J Biol Chem 279:13645–13651 [CrossRef]
    [Google Scholar]
  76. Winson M. K, Camara M, Latifi A. 7 other authors 1995; Multiple N -acyl-l-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa . Proc Natl Acad Sci U S A 92:9427–9431 [CrossRef]
    [Google Scholar]
  77. Wu H, Song Z, Hentzer M. 8 other authors 2000; Detection of N -acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa . Microbiology 146:2481–2493
    [Google Scholar]
  78. Yates E. A, Philipp B, Buckley C. 8 other authors 2002; 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 70:5635–5646 [CrossRef]
    [Google Scholar]
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