Skip to main content

Advertisement

Log in

Quorum sensing inhibitory drugs as next generation antimicrobials: Worth the effort?

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Bacterial resistance poses a major challenge to the development of new antimicrobial agents. Conventional antibiotics have an inherent obsolescence because they select for development of resistance. Bacterial infections have again become a serious threat in developed countries. Particularly, elderly, immunocompromised, and hospitalized patients are susceptible to infections caused by bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. These bacteria form chronic, biofilm-based infections, which are challenging because bacterial cells living as biofilms are more tolerant to antibiotics than their planktonic counterparts. Therefore, research should identify new antimicrobial agents and their corresponding targets to decrease the biofilm-forming capability or persistence of the infectious bacteria. Here, we review one such drug target: bacterial cell-to-cell communication systems, or quorum sensing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Cohen ML: Changing patterns of infectious disease. Nature 2000, 406:762–767.

    Article  PubMed  CAS  Google Scholar 

  2. Tomasz A: Control of the competent state in Pneumococcus by a hormone-like cell product: an example for a new type of regulatory mechanism in bacteria. Nature 1965, 208:155–159.

    Article  PubMed  CAS  Google Scholar 

  3. Nealson KH, Platt T, Hastings JW: Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 1970, 104:313–322.

    PubMed  CAS  Google Scholar 

  4. Fuqua WC, Winans SC, Greenberg EP: Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994, 176:269–275.

    PubMed  CAS  Google Scholar 

  5. Redfield RJ: Is quorum sensing a side effect of diffusion sensing? Trends Microbiol 2002, 10:365–370.

    Article  PubMed  CAS  Google Scholar 

  6. Soberon-Chavez G, Aguirre-Ramirez M, Ordonez L: Is Pseudomonas aeruginosa only “sensing quorum”? Crit Rev Microbiol 2005, 31:171–182.

    Article  PubMed  CAS  Google Scholar 

  7. Lerat E, Moran NA: The evolutionary history of quorumsensing systems in bacteria. Mol Biol Evol 2004, 21:903–913.

    Article  PubMed  CAS  Google Scholar 

  8. Fuqua C, Parsek MR, Greenberg EP: Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu Rev Genet 2001, 35:439–468.

    Article  PubMed  CAS  Google Scholar 

  9. Fuqua C, Winans SC, Greenberg EP: Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu Rev Microbiol 1996, 50:727–751.

    Article  PubMed  CAS  Google Scholar 

  10. Diggle SP, Winzer K, Chhabra SR, et al.: The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell densitydependency 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 2003, 50:29–43.

    Article  PubMed  CAS  Google Scholar 

  11. Schuster M, Greenberg EP: A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J Med Microbiol 2006, 296:73–81.

    Article  PubMed  CAS  Google Scholar 

  12. Winans SC, Bassler BL: Mob psychology. J Bacteriol 2002, 184:873–883.

    Article  PubMed  CAS  Google Scholar 

  13. Miller MB, Bassler BL: Quorum sensing in bacteria. Annu Rev Microbiol 2001, 55:165–199.

    Article  PubMed  CAS  Google Scholar 

  14. Winzer K, Hardie KR, Burgess N, et al.: LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone. Microbiology 2002, 148:909–922.

    PubMed  CAS  Google Scholar 

  15. Sun J, Daniel R, Wagner-Dobler I, Zeng AP: Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways. BMC Evol Biol 2004, 4:36.

    Article  PubMed  CAS  Google Scholar 

  16. Eberl L, Winson MK, Sternberg C, et al.: Involvement of N-acyl-L-hormoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens. Mol Microbiol 1996, 20:127–136.

    Article  PubMed  CAS  Google Scholar 

  17. Davies DG, Parsek MR, Pearson JP, et al.: The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 1998, 280:295–298.

    Article  PubMed  CAS  Google Scholar 

  18. 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-tocell signaling, and stationary-phase sigma factor expression. Appl Environ Microbiol 2002, 68:2008–2017.

    Article  PubMed  CAS  Google Scholar 

  19. Bjarnsholt T, Jensen PO, Burmolle M, et al.: Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 2005, 151:373–383.

    Article  PubMed  CAS  Google Scholar 

  20. Beatson SA, Whitchurch CB, Semmler AB, Mattick JS: Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J Bacteriol 2002, 184:3598–3604.

    Article  PubMed  CAS  Google Scholar 

  21. MacLehose HG, Gilbert P, Allison DG: Biofilms, homoserine lactones and biocide susceptibility. J Antimicrob Chemother 2004, 53:180–184.

    Article  PubMed  CAS  Google Scholar 

  22. Hentzer M, Eberl L, Givskov M: Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2005, 2:37–61.

    Article  Google Scholar 

  23. Kong KF, Vuong C, Otto M: Staphylococcus quorum sensing in biofilm formation and infection. Int J Med Microbiol 2006, 296:133–139.

    Article  PubMed  CAS  Google Scholar 

  24. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP: Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 2004, 186:1838–1850.

    Article  PubMed  CAS  Google Scholar 

  25. Donlan RM, Costerton JW: Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002, 15:167–193.

    Article  PubMed  CAS  Google Scholar 

  26. Bjarnsholt T, Kirketerp-Møller K, Kristiansen S, et al.: Silver against Pseudomonas aeruginosa biofilms. APMIS 2007, 115:921–928.

    Article  PubMed  CAS  Google Scholar 

  27. Hentzer M, Wu H, Andersen JB, et al.: Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 2003, 22:3803–3815.

    Article  PubMed  CAS  Google Scholar 

  28. Jensen PO, Bjarnsholt T, Phipps R, et al.: Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorumsensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 2007, 153:1329–1338.

    Article  PubMed  CAS  Google Scholar 

  29. Costerton JW, Stewart PS, Greenberg EP: Bacterial biofilms: a common cause of persistent infections. Science 1999, 284:1318–1322.

    Article  PubMed  CAS  Google Scholar 

  30. Favre-Bonte S, Pache JC, Robert J, et al.: Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients. Microb Pathog 2002, 32:143–147.

    Article  PubMed  CAS  Google Scholar 

  31. Baltimore RS, Christie CD, Smith GJ: Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration. Am Rev Respir Dis 1989, 140:1650–1661.

    PubMed  CAS  Google Scholar 

  32. Gjodsbol K, Christensen JJ, Karlsmark T, et al.: Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 2006, 3:225–231.

    Article  PubMed  Google Scholar 

  33. Bjarnsholt T, Kirketerp-Møller K, Jensen PO, et al.: Why chronic wounds won’t heal: a novel hypothesis. Wound Repair Regen 2007, [Epub ahead of print].

  34. Givskov M, de Nys R, Manefield M, et al.: Eukaryotic interference with homoserine lactonemediated prokaryotic signalling. J Bacteriol 1996, 178:6618–6622.

    PubMed  CAS  Google Scholar 

  35. Manefield M, Rasmussen TB, Henzter M, et al.: Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 2002, 148:1119–1127.

    PubMed  CAS  Google Scholar 

  36. Koch B, Liljefors T, Persson T, et al.: The LuxR receptor: the sites of interaction with quorum-sensing signals and inhibitors. Microbiology 2005, 151:3589–3602.

    Article  PubMed  CAS  Google Scholar 

  37. Hentzer M, Riedel K, Rasmussen TB, et al.: Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 2002, 148:87–102.

    PubMed  CAS  Google Scholar 

  38. 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 2004, 53:1054–1061.

    Article  PubMed  CAS  Google Scholar 

  39. Rasch M, Buch C, Austin B, et al.: An inhibitor of bacterial quorum sensing reduces mortalities caused by Vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum). Syst Appl Microbiol 2004, 27:350–359.

    Article  PubMed  CAS  Google Scholar 

  40. Christensen LD, Moser C, Jensen PO, et al.: The impact of Pseudomonas aeruginosa Quorum Sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model. Microbiology 2007, 153:2312–2320.

    Article  PubMed  CAS  Google Scholar 

  41. Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al.: Identity and effects of quorum sensing inhibitors produced by Penicillum species. Microbiology 2005, 151:1325–1340.

    Article  PubMed  CAS  Google Scholar 

  42. Bjarnsholt T, Jensen PO, Rasmussen TB, et al.: Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 2005, 151:3873–3880.

    Article  PubMed  CAS  Google Scholar 

  43. Balaban N, Cirioni O, Giacometti A, et al.: Treatment of Staphylococcus aureus biofilm infection by the quorumsensing inhibitor RIP. Antimicrob Agents Chemother 2007, 51:2226–2229.

    Article  PubMed  CAS  Google Scholar 

  44. Korem M, Gov Y, Kiran MD, Balaban N: Transcriptional profiling of target of RNAIII-activating protein, a master regulator of staphylococcal virulence. Infect Immun 2005, 73:6220–6228.

    Article  PubMed  CAS  Google Scholar 

  45. Yang G, Cheng H, Liu C, et al.: Inhibition of Staphylococcus aureus pathogenesis in vitro and in vivo by RAP-binding peptides. Peptides 2003, 24:1823–1828.

    Article  PubMed  CAS  Google Scholar 

  46. Gov Y, Bitler A, Dell’Acqua G, et al.: RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis. Peptides 2001, 22:1609–1620.

    Article  PubMed  CAS  Google Scholar 

  47. Nalca Y, Jansch L, Bredenbruch F, et al.: Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach. Antimicrob Agents Chemother 2006, 50:1680–1688.

    Article  PubMed  CAS  Google Scholar 

  48. Ichimiya T, Takeoka K, Hiramatsu K, et al.: The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro. Chemotherapy 1996, 42:186–191.

    Article  PubMed  CAS  Google Scholar 

  49. 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 P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr-/—mice. Antimicrob Agents Chemother 2007, 51:3677–3687.

    Article  PubMed  CAS  Google Scholar 

  50. Southern KW, Barker PM: Azithromycin for cystic fibrosis. Eur Respir J 2004, 24:834–838.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Givskov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bjarnsholt, T., Givskov, M. Quorum sensing inhibitory drugs as next generation antimicrobials: Worth the effort?. Curr Infect Dis Rep 10, 22–28 (2008). https://doi.org/10.1007/s11908-008-0006-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-008-0006-y

Keywords

Navigation