Applied Microbiology and Biotechnology

, Volume 99, Issue 7, pp 3303–3316 | Cite as

Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens

  • José A. Gutiérrez-Barranquero
  • F. Jerry Reen
  • Ronan R. McCarthy
  • Fergal O’Gara
Environmental biotechnology


The rapid unchecked rise in antibiotic resistance over the last few decades has led to an increased focus on the need for alternative therapeutic strategies for the treatment and clinical management of microbial infections. In particular, small molecules that can suppress microbial virulence systems independent of any impact on growth are receiving increased attention. Quorum sensing (QS) is a cell-to-cell signalling communication system that controls the virulence behaviour of a broad spectrum of bacterial pathogens. QS systems have been proposed as an effective target, particularly as they control biofilm formation in pathogens, a key driver of antibiotic ineffectiveness. In this study, we identified coumarin, a natural plant phenolic compound, as a novel QS inhibitor, with potent anti-virulence activity in a broad spectrum of pathogens. Using a range of biosensor systems, coumarin was active against short, medium and long chain N-acyl-homoserine lactones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key virulence systems were studied in the nosocomial pathogen Pseudomonas aeruginosa. Consistent with suppression of QS, coumarin inhibited biofilm, the production of phenazines and swarming motility in this organism potentially linked to reduced expression of the rhlI and pqsA quorum sensing genes. Furthermore, coumarin significantly inhibited biofilm formation and protease activity in other bacterial pathogens and inhibited bioluminescence in Aliivibrio fischeri. In light of these findings, coumarin would appear to have potential as a novel quorum sensing inhibitor with a broad spectrum of action.


Coumarin Natural compound Quorum sensing inhibition Anti-biofilm Bacterial pathogens 



This research was supported in part by grants awarded by the Science Foundation of Ireland (07/IN.1/B948, 12/TIDA/B2411, 12/TIDA/B2405, 09/RFP/BMT 2350, SSPC212/RC/2275); the Department of Agriculture, Fisheries and Food (FIRM/RSF/CoFoRD; DAFF11/F/009MabS); the Environmental Protection Agency (EPA 2008-PhD/S-2); the Irish Research Council for Science, Engineering and Technology (PD/2011/2414; RS/2010/2413); the European Commission (FP7-PEOPLE-2013-ITN, 607786; FP7-KBBE-2012-6, FP7-KBBE-2012-6, Marie Curie 256596); Marine Microbial Biodiversity, Bioinformatics and Biotechnology (MICRO B3)(OCEAN 2012 287589), Marine Microorganisms: Cultivation Methods for improving their Biotechnological Applications (MACUMBA)(CP-TP 311975), Increasing Value and Flow in the Marine Biodiscovery Pipeline (PharmaSea) (CP-TP 312184) and the Marine Institute (Beaufort award C2CRA 2007/082); Teagasc (Walsh Fellowship 2013) and the Health Research Board (HRA/2009/146).

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  1. Atkinson S, Williams P (2009) Quorum sensing and social networking in the microbial world. J R Soc Interface 6:959–978. doi: 10.1098/rsif.2009.0203 CrossRefPubMedCentralPubMedGoogle Scholar
  2. Bacalso M, Xu T, Yeung K, Zheng D (2011) Biofilm formation of Pseudomonas aeruginosa PA14 required lasI and was stimulated by the Pseudomonas Quinolone Signal although Salicylic acid Inhibition is independent of the pqs pathway. J Exp Microbiol Immun 15:84–89Google Scholar
  3. Baysse C, Cullinane M, Dénervaud V, Burrowes E, Dow JM, Morrissey JP, Tam L, Trevors JT, O’Gara F (2005) Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties. Microbiology 151:2529–2542. doi: 10.1099/mic. 0.28324-0 CrossRefPubMedGoogle Scholar
  4. Bjarnsholt T, Jensen P, Jakobsen TH, Phipps R, Nielsen AK, Rybtke MT, Tolker-Nielsen T, Givskov M, Høiby N, Ciofu O (2010) Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS One 5:e10115. doi: 10.1371/journal.pone.0010115 CrossRefPubMedCentralPubMedGoogle Scholar
  5. Bucolo C, Ward KW, Mazzon E, Cuzzocrea S, Drago F (2009) Protective effects of a coumarin derivative in diabetic rats. Invest Ophthalmol Vis Sci 50:3846–5382. doi: 10.1167/iovs. 08-3328 CrossRefPubMedGoogle Scholar
  6. Caiazza NC, Shanks RMQ, O’Toole GA (2005) Rhamnolipids modulate swarming motility patterns of Pseudomonas aeruginosa. J Bacteriol 187(21):7351–7361. doi: 10.1128/JB.187.21.7351 CrossRefPubMedCentralPubMedGoogle Scholar
  7. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ (2008) The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 6(1):17–27. doi: 10.1038/nrmicro1818 CrossRefPubMedCentralPubMedGoogle Scholar
  8. Choo JH, Rukayadi Y, Hwang JK (2006) Inhibition of bacterial quorum sensing by vanilla extract. Lett Appl Microbiol 42:637–641. doi: 10.1111/j.1472-765X.2006.01928.x PubMedGoogle Scholar
  9. Chu W, Zhou S, Jiang Y, Zhu W, Zhuang X, Fu J (2013) Effect of traditional chinese herbal medicine with antiquorum sensing activity on Pseudomonas aeruginosa. Evid Based Complement Alternat Med Volume 2013, Article ID 648257, 7 doi: 10.1155/2013/648257
  10. Cooper MA, Shlaes D (2011) Fix the antibiotics pipeline. Nature 472:32. doi: 10.1038/472032a CrossRefPubMedGoogle Scholar
  11. Daniels R, Vanderleyden J, Michiels J (2004) Quorum sensing and swarming migration in bacteria. FEMS Microbiol Rev 28:261–289. doi: 10.1016/j.femsre.2003.09.004 CrossRefPubMedGoogle Scholar
  12. Davies DG (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280:295–298. doi: 10.1126/science.280.5361.295 CrossRefPubMedGoogle Scholar
  13. De Kievit TR (2009) Quorum sensing in Pseudomonas aeruginosa biofilms. Environ Microbiol 11:279–288. doi: 10.1111/j.1462-2920.2008.01792.x CrossRefPubMedGoogle Scholar
  14. de Souza SM, Monache FD, Smânia A (2005) Antibacterial activity of coumarins. Z Naturforsch 60:693–700Google Scholar
  15. Devji T, Reddy C, Woo C, Awale S, Kadota S, Carrico-Moniz D (2011) Pancreatic anticancer activity of a novel geranylgeranylated coumarin derivative. Bioorg Med Chem Lett 21:57705773. doi: 10.1016/j.bmcl.2011.08.005 CrossRefGoogle Scholar
  16. Déziel E, Lépine F, Milot S, He J, Mindrinos MN, Tompkins RG, Rahme LG (2004) 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 USA 101:1339–1344. doi: 10.1073/pnas.0307694100 CrossRefPubMedCentralPubMedGoogle Scholar
  17. Dietrich LEP, Price-Whelan A, Petersen A, Whiteley M, Newman DK (2006) The phenazinepyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol Microbiol 61:1308–1321. doi: 10.1111/j.1365-2958.2006.05306.x CrossRefPubMedGoogle Scholar
  18. Dong YH, Xu JL, Li XZ, Zhang LH (2000) AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. Proc Natl Acad Sci 97:3526–3531. doi: 10.1073/pnas.97.7.3526 CrossRefPubMedCentralPubMedGoogle Scholar
  19. Farrand SK, Hwang I, Cook DM (1996) The tra region of the nopaline-type Ti plasmid is a chimera with elements related to the transfer systems of RSF1010, RP4, and F. J Bacteriol 178(14):4233–4247PubMedCentralPubMedGoogle Scholar
  20. Favre-Bonté S, Köhler T, Van Delden C (2003) Biofilm formation by Pseudomonas aeruginosa: role of the C4-HSL cell-to-cell signal and inhibition by azithromycin. J Antimicrob Chemother 52:598–604. doi: 10.1093/jac/dkg397 CrossRefPubMedGoogle Scholar
  21. Felter SP, Vassallo JD, Carlton BD, Daston GP (2006) A safety assessment of coumarin taking into account species-specificity of toxicokinetics. Food Chem Toxicol 44:462–475. doi: 10.1016/j.fct.2005.08.019 CrossRefPubMedGoogle Scholar
  22. Fernández L, Hancock REW (2012) Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 25:661–681. doi: 10.1128/CMR. 00043-12 CrossRefPubMedCentralPubMedGoogle Scholar
  23. Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN (2004) Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr Pharm Des 10:3813–3833. doi: 10.2174/1871520613666131224124445 CrossRefPubMedGoogle Scholar
  24. Girennavar B, Cepeda ML, Soni KA, Vikram A, Jesudhasan P, Jayaprakasha GK, Pillai SD, Patil BS (2008) Grapefruit juice and its furocoumarins inhibits autoinducersignaling and biofilm formation in bacteria. Int J Food Microbiol 125:204–208. doi: 10.1016/j.ijfoodmicro.2008.03.028 CrossRefPubMedGoogle Scholar
  25. Golfakhrabadi F, Abdollahi M, Ardakani MRS, Saeidnia S, Akbarzadeh T, Ahmadabadi AN, Ebrahimi A, Yousefbeyk F, Hassanzadeh A, Khanavi M (2014) Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats. Pharm Biol 52:1335–1340. doi: 10.3109/13880209.2014.892140 CrossRefPubMedGoogle Scholar
  26. González Barrios AF, Zuo R, Hashimoto Y, Yang L, Bentley WE, Wood TK (2006) Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022). J Bacteriol 188:305–316. doi: 10.1128/JB.188.1.305-316.2006 CrossRefPubMedCentralPubMedGoogle Scholar
  27. Gould IM (2009) Antibiotic resistance: the perfect storm. Int J Antimicrob Agents 34:52–55. doi: 10.1016/S0924-8579(09)70549-7 CrossRefGoogle Scholar
  28. Hanson JR (2003) The classes of natural product and their isolation. In: Abel EW (ed) Natural products: the secondary metabolites. Royal Society of Chemistry, Cambridge, pp 1–34CrossRefGoogle Scholar
  29. Häussler S, Becker T (2008) The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas aeruginosa populations. PLoS Pathog 4:e1000166. doi: 10.1371/journal.ppat.1000166
  30. Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song Z, Kristoffersen P, Manefield M, Costerton JW, Molin S, Eberl L, Steinberg P, Kjelleberg S, Høiby N, Givskov M (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815. doi: 10.1093/emboj/cdg366
  31. Høiby N, Ciofu O, Johansen HK, Song Z, Moser C, Jensen P, Molin S, Givskov M, Tolker-Nielsen T, Bjarnsholt T (2011) The clinical impact of bacterial biofilms. Int J Oral Sci 3:55–65. doi: 10.4248/IJOS11026 CrossRefPubMedCentralPubMedGoogle Scholar
  32. Jamier V, Marut W, Valente S, Chereau C, Chouzenoux S, Nicco C, Lemarechal H, Weill B, Kirsch G, Jacob C, Batteux F (2014) Chalcone-Coumarin derivatives as potential anti-cancer drugs: an in vitro and in vivo investigation. Anticancer Agents Med Chem 14(7):963–974. doi: 10.2174/1871520613666131224124445 CrossRefPubMedGoogle Scholar
  33. Kalia VC (2013) Quorum sensing inhibitors: an overview. Biotechnol Adv 31:224–245. doi: 10.1016/j.biotechadv.2012.10.004 CrossRefPubMedGoogle Scholar
  34. Kalia VC, Purohit HJ (2011) Quenching the quorum sensing system: potential antibacterial drug targets. Crit Rev Microbiol 37:121–140. doi: 10.3109/1040841X.2010.532479 CrossRefPubMedGoogle Scholar
  35. Kim C, Kim J, Park HY, Park HJ, Lee JH, Kim CK, Yoon J (2008) Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa. Appl Microbiol Biotechnol 80:37–47. doi: 10.1007/s00253-008-1474-6 CrossRefPubMedGoogle Scholar
  36. Koh CL, Sam CK, Yin WF, Tan LY, Krishnan T, Chong YM, Chan KG (2013) Plant-derived natural products as sources of anti-quorum sensing compounds. Sensors 13:6217–6228. doi: 10.3390/s130506217 CrossRefPubMedCentralPubMedGoogle Scholar
  37. Köhler T, Curty LK, Barja F, Delden CV, Pechère JC (2000) Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996. doi: 10.1128/JB.182.21.5990-5996.2000 CrossRefPubMedCentralPubMedGoogle Scholar
  38. Lake BG (1999) Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. Food Chem Toxicol 37:423–453. doi: 10.1016/S0278-6915(99)00010-1 CrossRefPubMedGoogle Scholar
  39. LaSarre B, Federle MJ (2013) Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 77:73–111. doi: 10.1128/MMBR. 00046-12 CrossRefPubMedCentralPubMedGoogle Scholar
  40. Lau GW, Hassett DJ, Ran H, Kong F (2004) The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10:599–606. doi: 10.1016/j.molmed.2004.10.002 CrossRefPubMedGoogle Scholar
  41. Lebrun I, Marques-Porto R, Pereira AS, Pereira A, Perpetuo EA (2009) Bacterial toxins: an overview on bacterial proteases and their action as virulence factors. Mini Rev Med Chem 9:820–828. doi: 10.2174/138955709788452603 CrossRefPubMedGoogle Scholar
  42. Lee JH, Kim YG, Cho HS, Ryu SY, Cho MH, Lee J (2014) Coumarins reduce biofilm formation and the virulence of Escherichia coli O157:H7. Phytomedicine 21:1037–1042. doi: 10.1016/j.phymed.2014.04.008 CrossRefPubMedGoogle Scholar
  43. Manefield M, Nys R, Kumar N, Read R, Givskov M, Steinberg P, Kjelleberg S (1999) 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 145:283–291. doi: 10.1099/13500872-145-2-283
  44. McCarthy RR, Mooij MJ, Reen FJ, Lesouhaitier O, O’Gara F (2014) A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa. Microbiology 160:1488–1500. doi: 10.1099/mic. 0.075291-0 CrossRefPubMedGoogle Scholar
  45. McClean KH, Winson MK, Fish L, Taylor A, Chhabra SR, Camara M, Daykin M, Lamb JH, Swift S, Bycroft BW, Stewart GSAB, Williams P (1997) Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acyl homoserine lactones. Microbiology 143:3703–3711. doi: 10.1099/00221287-143-12-3703
  46. McGrath S, Wade DS, Pesci EC (2004) Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS). FEMS Microbiol Lett 230:27–34. doi: 10.1016/S0378-1097(03)00849-8 CrossRefPubMedGoogle Scholar
  47. Miller JH (1992) A short course in bacterial genetics. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  48. Milton DL, Hardman A, Camara M, Chhabra SR, Bycroft BW, Stewart GS, Williams P (1997) Quorum sensing in Vibrio anguillarum: characterization of the vanI/vanR locus and identification of the autoinducer N-(3-Oxodecanoyl)-L-homoserine lactone. J Bacteriol 179:3004–3012Google Scholar
  49. Morohoshi T, Inaba T, Kato N, Kanai K, Ikeda T (2004) Identification of quorum-sensing signal molecules and the LuxRI homologs in fish pathogen Edwardsiella tarda. J Biosci Bioeng 98:274–281. doi: 10.1016/S1389-1723(04)00281-6
  50. Ng WL, Bassler BL (2009) Bacterial quorum-sensing network architectures. Annu Rev Genet 43:197–222. doi: 10.1146/annurev-genet-102108-134304 CrossRefPubMedCentralPubMedGoogle Scholar
  51. Njoroge J, Sperandio V (2009) Jamming bacterial communication: new approaches for the treatment of infectious diseases. EMBO Mol Med 1:201–210. doi: 10.1002/emmm.200900032 CrossRefPubMedCentralPubMedGoogle Scholar
  52. O’Toole GA, Kolter R (1998) Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis. Mol Microbiol 28:449–461. doi: 10.1046/j.1365-2958.1998.00797.x CrossRefPubMedGoogle Scholar
  53. Ochsner UA, Fiechter A, Reisers J (1994) Isolation, characterization, and expression in Escherichia coli of the Pseudomonas aeruginosa rhlAB genes encoding a rhamnosyl transferase involved in rhamnolipid biosurfactant synthesis. J Biol Chem 269:19787–19795PubMedGoogle Scholar
  54. Ojala T, Remes S, Haansuu P, Vuorela H, Hiltunen R, Haahtela K, Vuorela P (2000) Antimicrobial activity of some coumarin containing herbal plants growing in Finland. J Ethnopharmacol 73:299–305. doi: 10.1016/S0378-8741(00)00279-8 CrossRefPubMedGoogle Scholar
  55. Payá M, Halliwell B, Hoult JR (1992) Interactions of a series of coumarins with reactive oxygen species. Scavenging of superoxide, hypochlorous acid and hydroxyl radicals. Biochem Pharmacol 44:205–214. doi: 10.1016/0006-2952(92)90002-Z CrossRefPubMedGoogle Scholar
  56. Periasamy S, Joo HS, Duong AC, Bach T-HL, Tan VY, Chatterjee SS, Cheung GYC, Otto M (2012) How Staphylococcus aureus biofilms develop their characteristic structure. Proc Natl Acad Sci USA 109:1281–1286. doi: 10.1073/pnas.1115006109 CrossRefPubMedCentralPubMedGoogle Scholar
  57. Pessi G, Williams F, Hindle Z, Heurlier K, Holden MT, Cámara M, Haas D, Williams P (2001) The global posttranscriptional regulator RsmA modulates production of virulence determinants and N-acylhomoserine lactones in Pseudomonas aeruginosa. J Bacteriol 183:6676–6683. doi: 10.1128/JB.183.22.6676-6683.2001 CrossRefPubMedCentralPubMedGoogle Scholar
  58. Poulter S, Carlton TM, Su X, Spring DR, Salmond GPC (2010) Engineering of new prodigiosin-based biosensors of Serratia for facile detection of short-chain N-acyl homoserine lactone quorum-sensing molecules. Environ Microbiol Rep 2:322–328. doi: 10.1111/j.1758-2229.2010.00140.x
  59. Price-Whelan A, Dietrich LEP, Newman DK (2006) Rethinking “secondary” metabolism: physiological roles for phenazine antibiotics. Nat Chem Biol 2:71–78. doi: 10.1038/nchembio764
  60. Ramos I, Dietrich LEP, Price-Whelan A, Newman DK (2010) Phenazines affect biofilm formation by Pseudomonas aeruginosa in similar ways at various scales. Res Microbiol 161:187–191. doi: 10.1016/j.resmic.2010.01.003 CrossRefPubMedCentralPubMedGoogle Scholar
  61. Rasmussen TB, Givskov M (2006) Quorum sensing inhibitors: a bargain of effects. Microbiology 152:895–904. doi: 10.1099/mic. 0.28601-0 CrossRefPubMedGoogle Scholar
  62. Ruby EG (1996) Lessons from a cooperative, bacterial-animal association: the Vibrio fischeri-Euprymna scolopes light organ symbiosis. Annu Rev Microbiol 50:591–624. doi: 10.1146/annurev.micro.50.1.591
  63. Rutherford ST, Bassler BL (2012) Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. doi: 10.1101/cshperspect.a012427 PubMedCentralPubMedGoogle Scholar
  64. Savoia D (2012) Plant-derived antimicrobial compounds: alternatives to antibiotics. Future Microbiol 7(8):979–990. doi: 10.2217/fmb.12.68 CrossRefPubMedGoogle Scholar
  65. Schertzer JW, Boulette ML, Whiteley M (2009) More than a signal: non-signaling properties of quorum sensing molecules. Trends Microbiol 17:189–195. doi: 10.1016/j.tim.2009.02.001 CrossRefPubMedGoogle Scholar
  66. Shrout JD, Chopp DL, Just CL, Hentzer M, Givskov M, Parsek MR (2006) The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol Microbiol 62:1264–1277. doi: 10.1111/j.1365-2958.2006.05421.x CrossRefPubMedGoogle Scholar
  67. Slater H, Crow M, Everson L, Salmond GPC (2003) Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and carbapenem, in Serratia via both quorum-sensing-dependent and -independent pathways. Mol Microbiol 47:303–320. doi: 10.1046/j.1365-2958.2003.03295.x CrossRefPubMedGoogle Scholar
  68. Solano C, Echeverz M, Lasa I (2014) Biofilm dispersion and quorum sensing. Curr Opin Microbiol 18:96–104. doi: 10.1016/j.mib.2014.02.008 CrossRefPubMedGoogle Scholar
  69. Suppiger A, Schmid N, Aguilar C, Pessi G, Eberl L (2013) Two quorum sensing systems control biofilm formation and virulence in members of the Burkholderia cepacia complex. Virulence 4:400–409. doi: 10.4161/viru.25338
  70. Surette MG, Miller MB, Bassler BL (1999) Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A new family of genes responsible for autoinducer production. Proc Natl Acad Sci USA 96:1639–1644. doi: 10.1073/pnas.96.4.1639
  71. Tanwar J, Das S, Fatima Z, Hameed S (2014) Multidrug resistance: an emerging crisis. Interdiscip Perspect Infect Dis Article ID 541340, 7 doi:  10.1155/2014/541340
  72. Vanamala J, Leonardi T, Patil BS, Taddeo SS, Murphy ME, Pike LM, Chapkin RS, Lupton JR, Turner ND (2006) Suppression of colon carcinogenesis by bioactive compounds in grapefruit. Carcinogenesis 27:1257–1265. doi: 10.1093/carcin/bgi318 CrossRefPubMedGoogle Scholar
  73. Vattem DA, Mihalik K, Crixell SH, McLean RJC (2007) Dietary phytochemicals as quorum sensing inhibitors. Fitoterapia 78:302–310. doi: 10.1016/j.fitote.2007.03.009 CrossRefPubMedGoogle Scholar
  74. Venugopala KN, Rashmi V, Odhav B (2013) Review on natural coumarin lead compounds for their pharmacological activity. Biomed Res IntArticle ID 963248, 14 doi:  10.1155/2013/963248
  75. Verstraeten N, Braeken K, Debkumari B, Fauvart M, Fransaer J, Vermant J, Michiels J (2008) Living on a surface: swarming and biofilm formation. Trends Microbiol 16:496–506. doi: 10.1016/j.tim.2008.07.004 CrossRefPubMedGoogle Scholar
  76. Wilder CN, Diggle SP, Schuster M (2011) Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems. ISME J 5:1332–1343. doi: 10.1038/ismej.2011.13 CrossRefPubMedCentralPubMedGoogle Scholar
  77. Yang L, Nilsson M, Gjermansen M, Givskov M, Tolker-Nielsen T (2009) Pyoverdine and PQS mediated subpopulation interactions involved in Pseudomonas aeruginosa biofilm formation. Mol Microbiol 74(6):1380–1392. doi: 10.1111/j.1365-2958.2009.06934.x CrossRefPubMedGoogle Scholar
  78. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP (2004) Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 186:1838–1850. doi: 10.1128/JB.186.6.1838-1850.2004 CrossRefPubMedCentralPubMedGoogle Scholar
  79. Yin WF, Purmal K, Chin S, Chan XY, Chan KG (2012) Long chain N-acyl homoserine lactone production by Enterobacter sp. isolated from human tongue surfaces. Sensors 12:14307–14314. doi: 10.3390/s121114307 CrossRefPubMedCentralPubMedGoogle Scholar
  80. Zeng Z, Qian L, Cao L, Tan H, Huang Y, Xue X, Shen Y, Zhou S (2008) Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa. Appl Microbiol Biotechnol 79:119–126. doi: 10.1007/s00253-008-1406-5 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • José A. Gutiérrez-Barranquero
    • 1
  • F. Jerry Reen
    • 1
  • Ronan R. McCarthy
    • 1
  • Fergal O’Gara
    • 1
    • 2
  1. 1.BIOMERIT Research Centre, School of MicrobiologyUniversity College Cork, National University of IrelandCorkIreland
  2. 2.School of Biomedical SciencesCurtin UniversityPerthAustralia

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