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.
Similar content being viewed by others
References and Recommended Reading
Cohen ML: Changing patterns of infectious disease. Nature 2000, 406:762–767.
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.
Nealson KH, Platt T, Hastings JW: Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 1970, 104:313–322.
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.
Redfield RJ: Is quorum sensing a side effect of diffusion sensing? Trends Microbiol 2002, 10:365–370.
Soberon-Chavez G, Aguirre-Ramirez M, Ordonez L: Is Pseudomonas aeruginosa only “sensing quorum”? Crit Rev Microbiol 2005, 31:171–182.
Lerat E, Moran NA: The evolutionary history of quorumsensing systems in bacteria. Mol Biol Evol 2004, 21:903–913.
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.
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.
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.
Schuster M, Greenberg EP: A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J Med Microbiol 2006, 296:73–81.
Winans SC, Bassler BL: Mob psychology. J Bacteriol 2002, 184:873–883.
Miller MB, Bassler BL: Quorum sensing in bacteria. Annu Rev Microbiol 2001, 55:165–199.
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.
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.
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.
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.
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.
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.
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.
MacLehose HG, Gilbert P, Allison DG: Biofilms, homoserine lactones and biocide susceptibility. J Antimicrob Chemother 2004, 53:180–184.
Hentzer M, Eberl L, Givskov M: Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2005, 2:37–61.
Kong KF, Vuong C, Otto M: Staphylococcus quorum sensing in biofilm formation and infection. Int J Med Microbiol 2006, 296:133–139.
Yarwood JM, Bartels DJ, Volper EM, Greenberg EP: Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 2004, 186:1838–1850.
Donlan RM, Costerton JW: Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002, 15:167–193.
Bjarnsholt T, Kirketerp-Møller K, Kristiansen S, et al.: Silver against Pseudomonas aeruginosa biofilms. APMIS 2007, 115:921–928.
Hentzer M, Wu H, Andersen JB, et al.: Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 2003, 22:3803–3815.
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.
Costerton JW, Stewart PS, Greenberg EP: Bacterial biofilms: a common cause of persistent infections. Science 1999, 284:1318–1322.
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.
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.
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.
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].
Givskov M, de Nys R, Manefield M, et al.: Eukaryotic interference with homoserine lactonemediated prokaryotic signalling. J Bacteriol 1996, 178:6618–6622.
Manefield M, Rasmussen TB, Henzter M, et al.: Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 2002, 148:1119–1127.
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.
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.
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.
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.
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.
Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al.: Identity and effects of quorum sensing inhibitors produced by Penicillum species. Microbiology 2005, 151:1325–1340.
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.
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.
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.
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.
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.
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.
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.
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.
Southern KW, Barker PM: Azithromycin for cystic fibrosis. Eur Respir J 2004, 24:834–838.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11908-008-0006-y