Marine Organisms as Source of Quorum Sensing Inhibitors



The search for novel anti-infective agents is an important element in combating threat posed by the multi-drug resistant bacterial pathogens. Due to slow progress in discovery and registration of novel class of antibiotics, alternate strategies such as blocking cell-cell communication called quorum sensing (QS) is identified as a novel anti-pathogenic drug target. In the recent years, excellent review articles have been published indicating potential of QS inhibitors (QSIs) from natural products including microbes, algae, fungi, as well as plants. However, first discovery of QS inhibitors was reported from marine algae Delisea pulchra, little focus has been given to explore marine organisms and their potential to yield QSIs of therapeutic value. Marine organisms are well known for their contribution to provide thousands of biologically active compounds. In this chapter, we have made an attempt to summarize the reports on the anti-QS properties of marine organisms and the nature of their derived compounds and their future perspectives.


Quorum Sense Kojic Acid Quorum Sense System Homoserine Lactone Rhamnolipid Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge the financial support provided by the Department of Science and Technology (DST), New Delhi, India, for awarding INSPIRE fellowship to FMH.


  1. Abed RMM, Dobretsov S, Al-Fori M, Gunasekera SP, Sudesh K, Paul VJ (2013) Quorum-sensing inhibitory compounds from extremophilic microorganisms isolated from a hypersaline cyanobacterial mat. J Ind Microbiol Biotechnol 40:759–772PubMedCrossRefGoogle Scholar
  2. Adonizio A, Kong KF, Mathee K (2008) Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by south Florida plant extracts. Antimicrob Agents Chemother 52:198–203PubMedCrossRefPubMedCentralGoogle Scholar
  3. Ahmad I, Aqil F, Ahmad F, Zahin M, Musarrat J (2008) Quorum sensing in bacteria: Potential in plant health protection. In: Ahmad I et al (eds) Plant–bacteria interactions. Wiley-VCH Verlag GmbH & Co. KGa, Weinheim, pp 129–153. ISBN 978-3-527-31901-5CrossRefGoogle Scholar
  4. Annapoorani A, Jabbar AKKA, Pandian SK, Ravi AV (2012) Inhibition of quorum sensing mediated virulence factors production in urinary pathogen Serratia marcescens PS1 by marine sponges. Ind J Microbiol 52(2):160–166CrossRefGoogle Scholar
  5. Aqil F, Ahmad I, Owais M (2006) Targeted screening of bioactive plant extracts and phytocompounds against problematic groups of Multidrug resistant bacteria. In: Modern Phytomedicine: turning medicinal plants into drugs. Wiley VCH, Weinheim, pp 173–197CrossRefGoogle Scholar
  6. Borchardt SA, Allain EJ, Michels JJ, Stearns GW, Kelly RF, McCoy WF (2001) Reaction of acylated homoserine lactone bacterial signaling molecules with oxidized halogen antimicrobials. Appl Environ Microbiol 67(7):3174–3179PubMedCrossRefPubMedCentralGoogle Scholar
  7. Cam DTV, Nhan DT, Ceuppens S, Hao NV, Dierckens K, Wille M, Sorgeloos P, Bossier P (2009) Effect of N-acyl homoserine lactone degrading enrichment cultures on Macrobrachium rosenbergii larviculture. Aquaculture 294:5–13CrossRefGoogle Scholar
  8. Clark BR, Engene N, Teasdale ME, Rowley DC, Matainaho T, Valeriote FA, Gerwick WH (2008) Natural products chemistry and taxonomy of the marine cyanobacterium Blennothrix cantharidosmum. J Nat Prod 71:1530–1537PubMedCrossRefPubMedCentralGoogle Scholar
  9. Das S, Ward LR, Burke C (2008) Prospects of using marine actinobacteria as probiotics in aquaculture. Appl Microbiol Biotechnol 81:419–429PubMedCrossRefGoogle Scholar
  10. de Nys R, Givskov M, Kumar N, Kjelleberg S, Steinberg PD (2006) Furanones. Prog Mol Subcell Biol 42:55–86PubMedGoogle Scholar
  11. Defoirdt T, Crab R, Wood TK, Sorgeloos P, Verstraete W, Bossier P (2006) Quorum sensing-disrupting brominated furanones protect the gnotobiotic brine shrimp Artemia franciscana from pathogenic Vibrio harveyi, Vibrio campbelii and Vibrio parahaemolyticus isolates. Appl Environ Microbiol 72(9):6419–6423PubMedCrossRefPubMedCentralGoogle Scholar
  12. Defoirdt T, Miyamoto CM, Wood TK, Meighen EA, Sorgeloos P, Verstraete W, Bossier P (2007) The natural furanone (5Z)-4bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone disrupts quorum sensing-regulated gene expression in Vibrio harveyi by decreasing the DNA-binding activity of the transcriptional regulator protein luxR. Environ Microbiol 9(10):2486–2495PubMedCrossRefGoogle Scholar
  13. Dobretsov S, Teplitski M, Alagely A, Gunasekara SP, Paul VJ (2010) Malyngolide from the cyanobacterium Lyngbya majuscula interferes with quorum sensing circuitry. Environ Microbiol Rep 2:739–744PubMedCrossRefGoogle Scholar
  14. Dobretsov S, Teplitski M, Bayer M, Gunasekera S, Proksch P, Paul VJ (2011) Inhibition of marine biofouling by bacterial quorum sensing inhibitors. Biofouling 27:893–905PubMedCrossRefPubMedCentralGoogle Scholar
  15. Dong YH, Gusti AR, Zhang Q, Xu JL, Zhang LH (2002) Identification of quorum-quenching N-acyl homoserine lactonases from Bacillus species. Appl Environ Microbiol 68:1754–1759PubMedCrossRefPubMedCentralGoogle Scholar
  16. Dudler R, Elberl E (2006) Interactions between bacteria and eukaryotes via small molecules. Curr Opin Biotechnol 17:268–273PubMedCrossRefGoogle Scholar
  17. Dworjanyn SA, Steinberg P (1999) Localisation and surface quantitation of secondary metabolites in the red alga Delisea pulchra. Mar Biol 133:727–736CrossRefGoogle Scholar
  18. Fenical W, Jensen PR (2006) Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2:666–673PubMedCrossRefGoogle Scholar
  19. Fuqua WC, Winans SC, Greenberg EP (1994) Quorum sensing in bacteria-the LuxR-LuxI family of cell density responsive transcriptional regulators. J Bacteriol 176:269–275PubMedPubMedCentralGoogle Scholar
  20. Gambello MJ, Kaye S, Iglewski BH (1993) LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxinA expression. Infect Immun 61:1180–1184PubMedPubMedCentralGoogle Scholar
  21. Givskov M, De Nys R, Manefield M, Gram L, Maximilien R, Eberl L, Molin S, Steinberg PD, Kjelleberg S (1996) Eukaryotic interference with homoserine lactone-mediated prokaryotic signaling. J Bacteriol 178:6618–6622PubMedPubMedCentralGoogle Scholar
  22. Gram L, de Nys R, Maximilien R, Givskov SP, Kjelleberg S (1996) Inhibitory effects of secondary metabolites from the red alga Delisea pulchra on swarming motility of Proteus mirabilis. Appl Environ Microbiol 62(11):4284–4287PubMedPubMedCentralGoogle Scholar
  23. Harper MK, Bugni TS, Copp BR, James RD, Lindsay BS, Richardson AD, Schnabel PC, Tasdemir D, VanWagoner RM, Verbitski SM, Ireland CM (2001) Introduction to the chemical ecology of marine natural products. Mar Chem Ecol: 3–69Google Scholar
  24. Hentzer M, Givskov M (2003) Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 112:1300–1307PubMedCrossRefPubMedCentralGoogle Scholar
  25. Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, Parsek MR, Rice SA, Eberl L, Molin S, Høiby N, Kjelleberg S, Michael G (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148(1):87–102PubMedGoogle Scholar
  26. Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song Z, Kristofferson P, Manefield M, Costerton JW, Moiln S, Eberl L, Steinberg P, Kjelleberg S, Hoiby N, Givskov M (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815PubMedCrossRefPubMedCentralGoogle Scholar
  27. Husain FM, Ahmad I, Asif M, Tahseen Q (2013) Influence of clove oil on certain quorum sensing regulated functions and biofilm of Pseudomonas aeruginosa and Aeromonas hydrophila. J Biosci 38:1–10CrossRefGoogle Scholar
  28. Jha B, Kumari K, Westphal J, Hartmann A, Schmidtt-Koplin P (2013) Quorum sensing inhibition by Asparagopsis taxiformis, a marine macro alga: separation of the compounds that interrupts bacterial communication. Mar Drugs 11:253–265PubMedCrossRefPubMedCentralGoogle Scholar
  29. Kalia VC (2013) Quorum sensing inhibitors: an overview. Biotechnol Adv 31:224–245PubMedCrossRefGoogle Scholar
  30. Kanagasabhapathy M, Yamazaki G, Ishida A, Sasaki H, Nagata S (2009) Presence of quorum-sensing inhibitor-like compounds from bacteria isolated from brown alga Colpomenia sinosa. Lett Appl Microbiol 49:573–579PubMedCrossRefGoogle Scholar
  31. Khan MSA, Zahin M, Hasan S, Husain FM, Ahmad I (2009) Inhibition of quorum sensing regulated bacterial functions by plant essential oils with special reference to clove oil. Lett Appl Microbiol 49:354–360PubMedCrossRefGoogle Scholar
  32. Kim JS, Kim YH, Seo YW, Park S (2007) Quorum sensing inhibitors from the red alga, Ahnfeltiopsis flabelliformis. Biotechnol Bioprocess Eng 12:308–311CrossRefGoogle Scholar
  33. Kjelleberg S, Steinberg P (2001) Defences against bacterial colonization of marine plants. In: Lindow SE, Hect-Poinar E, Elliot V (eds) Phyllosphere microbiology. APS Press, St. Paul, pp 157–172Google Scholar
  34. Kwan JC, Teplitski M, Gunasekara SP, Paul VJ, Luesch H (2010) Isolation and biological evaluation of 8-epi-malyngamide C from the Floridian marine cyanobacterium Lyngbya majuscula. J Nat Prod 73:463–466PubMedCrossRefPubMedCentralGoogle Scholar
  35. Kwan JC, Meickle T, Ladwa D, Teplitski M, Paul V, Luesch H (2011) Lyngbyoic acid, a “tagged” fatty acid from marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa. Mol Biosyst 7:1205–1216PubMedCrossRefPubMedCentralGoogle Scholar
  36. LaSarre B, Federle MJ (2013) Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 77:73–111PubMedCrossRefPubMedCentralGoogle Scholar
  37. Majik MS, Naika D, Bhatb C, Tilveb S, Tilvia S, D’Souzaa L (2013) Synthesis of (R)-Norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa. Bioorg Med Chem Lett 23:2353–2356PubMedCrossRefGoogle Scholar
  38. Manefield M, de 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+ 145:283–291PubMedGoogle Scholar
  39. Manefield M, Harris L, Rice SA, de Nys R, Kjelleberg S (2000) Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists. Appl Environ Microbiol 66(5):2079–2084PubMedCrossRefPubMedCentralGoogle Scholar
  40. Manefield M, Rasmussen TB, Henzter M (2002) Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 148(4):1119–1127PubMedGoogle Scholar
  41. Marris E (2006) Marine natural products: drugs from the deep. Nature 443:904–905PubMedCrossRefGoogle Scholar
  42. Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199PubMedCrossRefGoogle Scholar
  43. Morohoshi T, Ebata A, Nakazawa S, Kato N, Ikeda T (2005) N-Acylhomoserine lactone-producing or degrading bacteria isolated from the intestinal microbial flora of Ayu fish (Plecoglossus altivelis). Microbes Environ 20(4):264–268CrossRefGoogle Scholar
  44. Morohoshi T, Nakazawa S, Ebata A, Kato N, Ikeda T (2008) Identification and characterization of N-acylhomoserine lactone acylase from the fish intestinal Shewanella sp. strain MIB015. Biosci Biotechnol Biochem 72(7):1887–1893PubMedCrossRefGoogle Scholar
  45. Musthafa KS, Saroja V, Pandian SK, Ravi AV (2011) Antipathogenic potential of marine Bacillus sp. SS4on N-acyl-homoserine-lactone-mediated virulence factors production in Pseudomonas aeruginosa (PAO1). J Biosci 36:55–67PubMedCrossRefGoogle Scholar
  46. Musthafa KS, Pandian SK, Ravi AV (2012) Inhibition of quorum-sensing-dependent phenotypic expression in Serratia marcescens by marine sediment Bacillus spp. SS4. Ann Microbiol 62:443–447CrossRefGoogle Scholar
  47. Natrah FMI, Defoirdt T, Sorgeloos P, Bossier P (2011) Disruption of bacterial cell-to-cell communication by marine organisms and its relevance to aquaculture. Mar Biotechnol 13:109–126PubMedCrossRefGoogle Scholar
  48. Newman DJ, Cragg GM (2004a) Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 67:1216–1238PubMedCrossRefGoogle Scholar
  49. Newman DJ, Cragg GM (2004b) Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Curr Med Chem 11:1693–1713PubMedCrossRefGoogle Scholar
  50. Nielsen A, Mansson M, Bojer MS, Gram L, Larsen TO, Novick RP, Frees D, Frøkiær H, Ingmer H (2014) Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils. PLoS One 9(1):e84992PubMedCrossRefPubMedCentralGoogle Scholar
  51. Nithya C, Aravindraja C, Pandian SK (2010) Bacillus pumilus of Palk Bay origin inhibits quorum-sensing-mediated virulence factors in Gram-negative bacteria. Res Microbiol 161:293–304PubMedCrossRefGoogle Scholar
  52. Nylund GM, Cervin G, Hermansson M, Pavia H (2005) Chemical inhibition of bacterial colonization by the red algae Bonnemaisonia hamifera. Mar Ecol Prog Ser 302:27–36CrossRefGoogle Scholar
  53. Park SY, Kang HO, Jang HS, Lee JK, Koo BT, Yum DY (2005) Identification of extracellular N-acylhomoserine lactone acylase from a Streptomyces sp. and its application to quorum quenching. Appl Environ Microbiol 71:2632–2641PubMedCrossRefPubMedCentralGoogle Scholar
  54. Paterson I, Anderson EA (2005) The renaissance of natural products as drug candidates. Science 310:451–453PubMedCrossRefGoogle Scholar
  55. Peters L, Konig GM, Wright AD, Pukall R, Stackebrandt E, Eberl L, Riedel K (2003) Secondary metabolites of Flustra foliacea and their influence on bacteria. Appl Environ Microbiol 69:3469–3475PubMedCrossRefPubMedCentralGoogle Scholar
  56. Proksch P, Edrada RA, Ebel R (2002) Drugs from the seas-current status and microbiological implications. Appl Microbiol Biotechnol 59(2–3):125–134PubMedCrossRefGoogle Scholar
  57. Rasch M, Buch C, Austin B, Slierendrecht WJ, Ekmann KS, Larsen JL, Johansen C, Riedel K, Eberl L, Givskov M, Gram L (2004) An inhibitor of bacterial quorum sensing reduces mortalities caused by vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum). Syst Appl Microbiol 27:350–359PubMedCrossRefGoogle Scholar
  58. Rasmussen TB, Manefield M, Andersen JB, Eberl L, Anthoni U, Christopherse C, Steinberg P, Kjelleberg S, Givskov M (2000) How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1. Microbiology+ 146:3237–3244PubMedGoogle Scholar
  59. Rasmussen TB, Bjarnsholt BT, Skindersoe ME, Hentzer M, Kristoffersen P, Kote M, Nielsen J, Eberl L, Givskov M (2005) Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187:1799–1814PubMedCrossRefPubMedCentralGoogle Scholar
  60. Rasmussen TB, Givskov M (2006) Quorum sensing inhibitors: a bargain of effects. Microbiology 152:895–904PubMedCrossRefGoogle Scholar
  61. Reacher MH, Shah A, Livermore DM, Wale MC, Graham C, Johnson AP, Heine H, Monnickendam MA, Barker KF, James D, George RC (2000) Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. Br Med J 320:213–216CrossRefGoogle Scholar
  62. Ren D, Sims J, Wood TK (2001) Inhibition of biofilm formation and swarming of Escherichia coli by (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone. Environ Microbiol 3:731–736PubMedCrossRefGoogle Scholar
  63. Skindersoe ME, Ettinger-Epstein P, Rasmussen TB, Bjarnsholt T, deNys R, Givskov M (2008) Quorum sensing antagonism from marine organisms. Mar Biotechnol 10:56–63PubMedCrossRefGoogle Scholar
  64. Teasdale ME, Liu J, Wallace J, Akhlaghi F, Rowley DC (2009) Secondary metabolites produced by the marine bacterium Halobacillus salinus that inhibit quorum sensing-controlled phenotypes in Gram-negative bacteria. Appl Environ Microbiol 75:567–572PubMedCrossRefPubMedCentralGoogle Scholar
  65. Tenover FC, Hughes JM (1996) The challenges of emerging infectious diseases. Development and spread of multiply-resistant bacterial pathogens. JAMA 275:300–304PubMedCrossRefGoogle Scholar
  66. Teplitski M, Chen H, Rajamani S, Gao M, Merighi M, Sayre RT, Robinson JB, Rolfe BG, Bauer WD (2004) Chlamydomonas reinhardtii secretes compounds that mimic bacterial signals and interference with quorum sensing regulation in bacteria. Plant Physiol 134:137–146PubMedCrossRefPubMedCentralGoogle Scholar
  67. Tinh NTN, Gunasekara RAYS, Boon N, Dierckens K, Sorgeloos P, Bossier P (2007a) N-Acylhomoserine lactone degrading microbial enrichment cultures isolated from Penaeus vannamei shrimp gut and their probiotic properties in Brachionus plicatilis cultures. FEMS Microbiol Ecol 62:45–53PubMedCrossRefGoogle Scholar
  68. Tinh NTN, Lin ND, Wood TK, Dierckens K, Sorgeloos P, Bossier P (2007b) Interference with the quorum sensing systems in a Vibrio harveyi strain alters the growth rate of gnotobiotically cultured rotifer Brachionus plicatilis. J Appl Microbiol 103:194–203PubMedCrossRefGoogle Scholar
  69. Toder DS, Gambello MJ, Iglewski BH (1991) Pseudomonas aeruginosa LasA: a second elastase under the transcriptional control of lasR. Mol Microbiol 5:2003–2010PubMedCrossRefGoogle Scholar
  70. Williams P (2007) Quorum sensing, communication and cross kingdom signaling in the bacterial world. Microbiology 153:3923–3928PubMedCrossRefGoogle Scholar
  71. Wu H, Song Z et al (2004) Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 53(6):1054–1061Google Scholar
  72. You J, Xue X, Cao L, Lu X, Wang J, Zhang L, Zhou S (2007) Inhibition of Vibrio biofilm formation by a marine actinomycete strain A66. Appl Microbiol Cell Physiol 76:1137–1144Google Scholar
  73. Zahin M, Hasan S, Aqil F, Khan MSA, Husain FM, Ahmad I (2010) Screening of Indian medicinal plants for their anti-quorum sensing activity. Ind J Exp Biol 48:1219–1224Google Scholar
  74. Zang T, Lee BWK, Cannon LM, Ritter KA, Dai S, Ren D, Wood TK, Zhou ZS (2009) A naturally occurring brominated furanone covalently modifies and inactivates LuxS. Bioorg Med Chem Lett 19:6200–6204PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  1. 1.Department of Agricultural MicrobiologyAligarh Muslim UniversityAligarhIndia

Personalised recommendations