Biotechnological Applications of Quorum-Sensing Inhibitors in Aquacultures

  • Faseela Hamza
  • Ameeta Ravi Kumar
  • Smita Zinjarde


Aquaculture is an important food production sector that is estimated to increase rapidly in the future. This segment is challenged with issues such as disease outbreaks and emergence of antibiotic-resistant pathogenic strains. In most of the aquatic pathogens, the importance of quorum sensing for survival and development of virulence factors is well-documented. An understanding on the molecular basis of this phenomenon has led to the development of new strategies for disease control and a search for molecules interfering with related processes. This chapter briefly describes the quorum-sensing systems prevalent in the major aquaculture and aquatic pathogens Vibrio harveyi and Pseudomonas aeruginosa, details the structural features of quorum-sensing inhibitors (QSIs) of biological and chemical origin, discusses their mode of action, and highlights their use as alternative control agents. Such QSIs may in the future prove to be effective and sustainable alternatives and help in replacing the currently used antibiotics or sanitizers to some extent.


Quorum Sense Boronic Acid Kojic Acid Quorum Sense System Vibrio Species 
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.



All authors thank University Grants Commission for funding under UPE Phase II. FH thanks DST, India, for financial support under WOS-B scheme.


  1. Agersø Y, Bruun MS, Dalsgaard I, Larsen JL (2007) Tetracycline resistance gene tet(E) is frequently occurring and present on large horizontally transferable plasmids in Aeromonas spp. from fish farms. Aquaculture 266:47–52CrossRefGoogle Scholar
  2. Akinbowale OL, Peng H, Barton MD (2007) Diversity of tetracycline resistance genes in bacteria from aquaculture sources in Australia. J Appl Microbiol 103:2016–2025PubMedCrossRefGoogle Scholar
  3. Austin B, Zhang XH (2006) Vibrio harveyi: a significant pathogen of marine vertebrates and invertebrates. Lett Appl Microbiol 43:119–124PubMedCrossRefGoogle Scholar
  4. Ayyappan S, Jena JN (2001) Sustainable freshwater aquaculture in India. In: Pandian TJ (ed) Sustainable Indian fisheries. National Academy of Agricultural Sciences, New Delhi, pp 83–133Google Scholar
  5. Bartley DM, Bondad-Reantaso MG, Subasinghe RP (2006) A risk analysis framework for aquatic animal health management in marine stock enhancement programmes. Fish Res 80:28–36CrossRefGoogle Scholar
  6. Bell JD, Bartley DM, Lorenzen K, Loneragan NR (2006) Restocking and stock enhancement of coastal fisheries: potential, problems and progress. Fish Res 80:1–8CrossRefGoogle Scholar
  7. Bondad-Reantaso MG, Subasinghe RP, Arthur JR, Ogawa K, Chinabut S, Adlard R, Tan Z, Shariff M (2005) Disease and health management in Asian aquaculture. Vet Parasitol 132:249–272PubMedCrossRefGoogle Scholar
  8. Brackman G, Defoirdt T, Miyamoto C, Bossier P, Van Calenbergh S, Nelis H, Coenye T (2008) Cinnamaldehyde and cinnamaldehyde analogs reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR. BMC Microbiol 8:149PubMedCrossRefPubMedCentralGoogle Scholar
  9. Brackman G, Celen S, Baruah K, Bossier P, Van Calenbergh S, Nelis HJ, Coenye T (2009) AI-2 quorum sensing inhibitors affect the starvation response and reduce virulence in several Vibrio species, most likely by interfering with LuxPQ. Microbiology 155:4114–4122PubMedCrossRefGoogle Scholar
  10. Brackman G, Celen S, Hillaert U, Calenbergh SV, Cos P, Maes L, Nelis HJ, Coenye T (2011) Structure–activity relationship of cinnamaldehyde analogs as inhibitors of AI-2 based quorum sensing and their effect on virulence of Vibrio spp. PLoS One 6:1–10CrossRefGoogle Scholar
  11. Bruun MS, Schmidt AS, Madsen I, Dalsgaard I (2000) Antimicrobial resistance patterns in Danish isolates of Flavobacterium psychrophilum. Aquaculture 187:201–212CrossRefGoogle Scholar
  12. Cady NC, McKean KA, Behnke J (2012) Inhibition of biofilm formation, quorum sensing and infection in Pseudomonas aeruginosa by natural products-inspired organosulfur compounds. PLoS One 7:1–12CrossRefGoogle Scholar
  13. Cam DTV, Nhan DT, Ceuppens S, Hao NV, Dierckens K, Wille M, Sorgeloos P, Bossier P (2009a) Effect of N-acyl homoserine lactone-degrading enrichment cultures on Macrobrachium rosenbergii larviculture. Aquaculture 294:5–13CrossRefGoogle Scholar
  14. Cam DTV, Hao NV, Dierckens K, Defoirdt T, Boon N, Sorgeloos P, Bossier P (2009b) Novel approach of using homoserine lactone degrading and poly-β-hydroxybutyrate accumulating bacteria to protect Artemia from the pathogenic effects of Vibrio harveyi. Aquaculture 291:23–30CrossRefGoogle Scholar
  15. Campbell B, Pauly D (2013) Mariculture: a global analysis of production trends since 1950. Mar Policy 39:94–100CrossRefGoogle Scholar
  16. 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
  17. Costerton JW, Cheng KJ, Geesey GG, Ladd T, Nickel JC, Dasgupta M, Marrie TJ (1987) Bacterial biofilms in nature and disease. Annu Rev Microbiol 41:435–464PubMedCrossRefGoogle Scholar
  18. Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322PubMedCrossRefGoogle Scholar
  19. Dass BKM, Venugopal MN, Karunasagar I, Karunasagar I (2007) Bacteria associated with biofilms in a Macrobrachium rosenbergii hatchery. Asian Fish Sci 20:299–307Google Scholar
  20. De Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68:4839–4849PubMedCrossRefPubMedCentralGoogle Scholar
  21. 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 campbellii, and Vibrio parahaemolyticus isolates. Appl Environ Microbiol 72:6419–6423PubMedCrossRefPubMedCentralGoogle Scholar
  22. Defoirdt T, Miyamoto CM, Wood TK, Meighen EA, Sorgeloos P, Verstraete W, Bossier P (2007) The natural furanone (5Z)-4-bromo-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 9:2486–2495PubMedCrossRefGoogle Scholar
  23. Defoirdt T, Benneche T, Brackman G, Coenye T, Sorgeloos P, Scheie AA (2012) A quorum sensing-disrupting brominated thiophenone with a promising therapeutic potential to treat luminescent Vibriosis. PLoS One 7:1–7CrossRefGoogle Scholar
  24. Defoirdt T, Pande GSJ, Baruah K, Bossier P (2013) The apparent quorum sensing inhibitory activity of pyrogallol is a side effect of peroxide production. Antimicrob Agents Chemother. doi: 10.1128/AAC.00401-13 PubMedPubMedCentralGoogle Scholar
  25. 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
  26. Dunny GM, Leonard BAB (1997) Cell-cell communication in gram-positive bacteria. Annu Rev Microbiol 51:527–564PubMedCrossRefGoogle Scholar
  27. Dusane DH, Zinjarde SS, Venugopalan VP, McLean RJC, Weber MM, Rahman PKSM (2010) Quorum sensing: implications on rhamnolipid biosurfactant production. Biotechnol Genet Eng Rev 27:159–184PubMedCrossRefGoogle Scholar
  28. FAO (2012) The state of world fisheries and aquaculture 2012. U.N. Food and Agricultural Organization, RomeGoogle Scholar
  29. Faruque SM, Biswas K, Udden SM, Ahmad QS, Sack DA, Nair GB, Mekalanos JJ (2006) Transmissibility of cholera: in vivo-formed biofilms and their relationship to infectivity and persistence in the environment. Proc Natl Acad Sci USA 103:6350–6355PubMedCrossRefPubMedCentralGoogle Scholar
  30. Gonzalez SF, Krug MJ, Nielsen ME, Santos Y, Call DR (2004) Simultaneous detection of marine fish pathogens by using multiplex PCR and a DNA microarray. J Clin Microbiol 42:1414–1419PubMedCrossRefPubMedCentralGoogle Scholar
  31. Hall SJ, Hilborn R, Andrew NL, Allison EH (2013) Innovations in capture fisheries are an imperative for nutrition security in the developing world. Proc Natl Acad Sci USA 110:8393–8398PubMedCrossRefPubMedCentralGoogle Scholar
  32. Henke JM, Bassler BL (2004) Three parallel quorum–sensing systems regulate gene expression in Vibrio harveyi. J Bacteriol 186:6902–6914PubMedCrossRefPubMedCentralGoogle Scholar
  33. Husain FM, Ahmad I, Asif M, Tahseeni Q (2013) Influence of clove oil on certain quorum-sensing-regulated functions and biofilm of Pseudomonas aeruginosa and Aeromonas hydrophila. J Biosci 38:835–844PubMedCrossRefGoogle Scholar
  34. Jayaprakash NS, Kumar R, Philip VJ, Bright Singh IS (2006) Vibrios associated with Macrobrachium rosenbergii (De Man, 1879) larvae from three hatcheries on the Indian southwest coast. Aquac Res 37:351–358CrossRefGoogle Scholar
  35. Jayaraman A, Wood TK (2008) Bacterial quorum sensing: Signals, circuits, and implications for biofilms and disease. Annu Rev Biomed Eng 10:145–167PubMedCrossRefGoogle Scholar
  36. Jayasree LP, Janakiram PR, Madhavi R (1999) Shell disease in freshwater prawn Macrobrachium rosenbergii (de Man) aetiology, pathogenicity and antibiotic sensitivity. J Aquac Trop 14:289–298Google Scholar
  37. Joseph B, Otta SK, Karunasagar I, Karunasagar I (2001) Biofilm formation by Salmonella spp. on food contact surfaces and their sensitivity to sanitizers. Int J Food Microbiol 64:367–372PubMedCrossRefGoogle Scholar
  38. Kanagasabhapathy M, Yamazaki G, Ishida A, Sasaki H, Nagata S (2009) Presence of quorum-sensing inhibitor-like compounds from bacteria isolated from the brown alga Colpomenia sinuosa. Lett Appl Microbiol 49:573–579PubMedCrossRefGoogle Scholar
  39. Karunasagar I, Otta SK, Karunasagar I (1996) Biofilm formation by Vibrio harveyi on surfaces. Aquaculture 140:241–245CrossRefGoogle Scholar
  40. Kim J, Kim Y, Seo Y, Park S (2007) Quorum sensing inhibitors from the red alga, Ahnfeltiopsis flabelliformis. Biotechnol Bioprocess Eng 12:308–311CrossRefGoogle Scholar
  41. 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 80:37–47PubMedCrossRefGoogle Scholar
  42. King RK, Flick GJ, Smith SA, Pierson MD, Boardman GD, Coale CW (2008) Response of bacterial biofilms in recirculating aquaculture systems to various sanitizers. J Appl Aquac 20:79–92CrossRefGoogle Scholar
  43. Liu HB, Koh KP, Kim JS, Seo Y, Park S (2008) The effects of betonicine, floridoside, and isethionic acid from the red alga Ahnfeltiopsis flabelliformis on quorum-sensing activity. Bioprocess Biosyst Eng 13:458–463CrossRefGoogle Scholar
  44. Lombardi JV, Labao V (1991) Diseases and conditioning factors of mortality in larval culture of prawns of the genus Macrobrachium. In: Proceedings of the 3rd Brazilian symposium on shrimp culture, Joao Pes–sao, Paraiba, Brazil, pp 401–408Google Scholar
  45. Lundin CG (1996) Global attempts to address shrimp disease. Marine/Environmental paper no. 4 Land, Water and Natural Habitats Division, Environment Department, The World Bank, p 45Google Scholar
  46. 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 66:2079–2084PubMedCrossRefPubMedCentralGoogle Scholar
  47. Moriarty DJW (1998) Control of luminous Vibrio species in penaeid aquaculture ponds. Aquaculture 164:351–358CrossRefGoogle Scholar
  48. Müh U, Schuster M, Heim R, Singh A, Olson ER, Greenberg EP (2006) Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen. Antimicrob Agents Chemother 50:3674–3679PubMedCrossRefPubMedCentralGoogle Scholar
  49. Muroga K (2001) Viral and bacterial diseases of marine fish and shellfish in Japanese hatcheries. Aquaculture 202:23–44CrossRefGoogle Scholar
  50. Natrah FMI, Kenmegne MM, WiyotoW SP, Bossier P, Defoirdt T (2011) Effect of micro-algae commonly used in aquaculture on acyl homoserine lactone quorum sensing. Aquaculture 317:53–57CrossRefGoogle Scholar
  51. Nealson KH, Platt T, Hastings W (1970) Cellular control of the synthesis and activity of the bacterial biolumionescent system. J Bacteriol 104:313–322PubMedPubMedCentralGoogle Scholar
  52. Nhan DT, Cam DTV, Wille M, Defoirdt T, Bossier P, Sorgeloos P (2010) Quorum quenching bacteria protect Macrobrachium rosenbergii larvae from Vibrio harveyi infection. J Appl Microbiol 109:1007–1016PubMedCrossRefGoogle Scholar
  53. Ni N, Choudhary G, Li M, Wang B (2008) Pyrogallol and its analogs can antagonize bacterial quorum sensing in Vibrio harveyi. Bioorg Med Chem Lett 18:1567–1572PubMedCrossRefGoogle Scholar
  54. Ni V, Choudhary G, Li M, Wang B (2009a) A new phenothiazine structural scaffold as inhibitors of bacterial quorum sensing in Vibrio harveyi. Biochem Biophys Res Commun 382:153–156PubMedCrossRefGoogle Scholar
  55. Ni N, Choudhary G, Peng H, Li M, Chou HT, Lu CD, Gilbert ES, Wang B (2009b) Inhibition of quorum sensing in Vibrio harveyi by boronic acids. Chem Biol Drug Des 74:51–56PubMedCrossRefGoogle Scholar
  56. O’Loughlina CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler BL (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci USA 110:17981–17986CrossRefGoogle Scholar
  57. Olivier G (2002) Disease interactions between wild and cultured fish-perspectives from the American Northeast (Atlantic Provinces). Bull Eur Assoc Fish Pathol 22:103–108Google Scholar
  58. Otta SK, Karunasagar I, Karunasagar I (1999) Bacterial flora associated with shrimp culture ponds growing Penaeus monodon in India. J Aquac Trop 14:309–318Google Scholar
  59. Otta SK, Karunasagar I, Karunasagar I (2001) Bacterial flora associated with shrimp culture ponds, Penaeus monodon Fabricius hatcheries in India. J Appl Ichtyol 17:59–63CrossRefGoogle Scholar
  60. Pillai NGK, Katiha PK (2004) Evolution of fisheries and aquaculture in India. Niseema Printers and Publishers, KochiGoogle Scholar
  61. Skindersoe ME, Epstein PE, Rasmussen TB (2008) Quorum-sensing antagonism from marine organisms. Mar Biotechnol 10:56–63PubMedCrossRefGoogle Scholar
  62. Steenackers HP, Levin J, Janssens JC, De Weerdt A, Balzarini J, Vanderleyden J, De Vos DE, De Keersmaecker SC (2010) Structure-activity relationship of brominated 3-alkyl-5-methylene-2(5H)-furanones and alkylmaleic anhydrides as inhibitors of Salmonella biofilm formation and quorum sensing regulated bioluminescence in Vibrio harveyi. Bioorg Med Chem 18:5224–5233PubMedCrossRefGoogle Scholar
  63. Subasinghe R, Bartly DM, Mcgladdery S, Barg U (1998) Sustainable shrimp culture development: biotechnological issues and challenges. In: Flegel TW (ed) Advances in shrimp biotechnology. National Centre for Genetic Engineering and Biotechnology, Bangkok, pp 13–18Google Scholar
  64. Subasinghe RP, Bonad-Reantaso MG, McGladdery ME (2001) Aquaculture development, health and wealth. In: Subasinghe RP, Bueno P, Phillips MJ, Hough C, McGladdery SE, Arthur JR (eds), Aquaculture in the third millennium. Technical proceedings of the conference on aquaculture in the third millennium, Bangkok, Thailand, February 2000. Network of Aquaculture Centers in Asia and the Pacific, Bangkok, pp 167–192Google Scholar
  65. Swem LR, Swem DL, O’Loughlina CT, Gatmaitan R, Zhao B, Ulrich SM, Bassler BL (2009) A quorum–sensing antagonist targets both membrane–bound and cytoplasmic receptors and controls bacterial pathogenicity. Mol Cell 35:143–153PubMedCrossRefPubMedCentralGoogle Scholar
  66. Teplitki M, Robinson JB, Bauer WD (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 13:637–648CrossRefGoogle Scholar
  67. Teplitki M, Chen H, Rajamani S, Gao M, Merighi M, Sayre RT, Robinson JB, Rolfe BG, Bauer WD (2004) Chlamydomonas reinhardtii secretes compound that mimic bacterial signals and interfere with quorum sensing regulation in bacteria. Plant Physiol 134:137–146CrossRefGoogle Scholar
  68. Thompson FL, Abreu PC, Wasielesky W (2002) Importance of biofilm for water quality and nourishment in intensive shrimp culture. Aquaculture 203:263–278CrossRefGoogle Scholar
  69. Tinh NTN, Yen VHN, Dierckens K, Sorgeloos P, Bossier P (2008) An acyl homoserine lactone-degrading microbial community improves the survival of first feeding turbot larvae (Scophthalmus maximus L.). Aquaculture 285:56–62CrossRefGoogle Scholar
  70. Wai SN, Mizunoe Y, Takade A, Kawabata SI, Yoshida SI (1998) Vibrio cholerae O1 strain TSI-4 produces the exopolysaccharide materials that determine colony morphology, stress resistance, and biofilm formation. Appl Environ Microbiol 64:3648–3655PubMedPubMedCentralGoogle Scholar
  71. Wang SY, Lauritz J, Jass J, Milton DL (2003) Role for the major outer-membrane protein from Vibrio anguillarum in bile resistance and biofilm formation. Microbiology 149:1061–1071PubMedCrossRefGoogle Scholar
  72. Watnick PI, Kolter R (1999) Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol 34:586–595PubMedCrossRefPubMedCentralGoogle Scholar
  73. Watnick PI, Lauriano CM, Klose KE, Croal L, Kolter R (2001) The absence of a flagellum leads to altered colony morphology, biofilm development and virulence in Vibrio cholerae O139. Mol Microbiol 39:223–235PubMedCrossRefPubMedCentralGoogle Scholar
  74. Zhang XH, Austin B (2000) Pathogenicity of Vibrio harveyi to salmonids. J Fish Dis 23:93–102CrossRefGoogle Scholar
  75. Zhu J, Mekalanos JJ (2003) Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. Dev Cell 5:647–656PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2015

Authors and Affiliations

  • Faseela Hamza
    • 1
  • Ameeta Ravi Kumar
    • 1
  • Smita Zinjarde
    • 1
  1. 1.Institute of Bioinformatics and BiotechnologyUniversity of PunePuneIndia

Personalised recommendations