Quorum Sensing in Bacterial Pathogenesis and Virulence

  • Parasuraman Paramanantham
  • Subhaswaraj Pattnaik
  • Siddhardha Busi


Quorum sensing (QS) is a widespread and highly conserved cell-to-cell communication that coordinates the social instincts of bacteria and also regulates the gene expression in an efficient manner. The QS phenomenon relies upon the production and detection of highly specific chemical signaling molecules popularly known as autoinducers. The diversity of autoinducer molecules produced by bacteria enables the bacteria to communicate within the species level as well as in between the genus level when present beyond a particular threshold level of autoinducer in the environment. Gram-positive and Gram-negative bacteria specifically synthesize different kinds of autoinducers to control the expression of different genes. Pathogenic bacterial population exploit the high throughput signaling phenomenon to regulate genes for the process of invasion, defense and more importantly to generate virulence determinants such as toxins, enzymes and ultimately leads to the formation of biofilm. Biofilm formation has been well documented in most of the pathogenic bacteria utilizing the highly synchronized QS phenomena that will give the bacterial community an impinge to confer resistance against wide array of antibiotics and other antimicrobial drugs in an efficient manner thereby possess serious threat to immunocompromised individuals. The emergence of multi drug resistant pathogens and their ability to form biofilm, infers a current need for development of alternative therapeutic strategies towards the bacterial quorum sensing phenomenon.


Quorum sensing Biofilm Multidrug resistance Virulence Pathogenicity 


  1. 1.
    Annapoorani, A., Kalpana, B., Musthafa, K. S., Pandian, S. K., & Ravi, A. V. (2013). Antipathogenic potential of Rhizophora spp. against the quorum sensing mediated virulence factors production in drug resistant Pseudomonas aeruginosa. Phytomedicine, 20, 956–963.CrossRefGoogle Scholar
  2. 2.
    Ansari, M. A., Khan, H. M., Khan, A. A., Cameotra, S. S., Saquib, Q., & Mussarat, J. (2014). Gum arabic capped-silver nanoparticles inhibit biofilm formation by multi-drug resistant strains of Pseudomonas aeruginosa. Journal of Basic Microbiology, 54, 688–699.CrossRefGoogle Scholar
  3. 3.
    Antunes, L. C. M., Ferreira, R. B. R., Buckner, M. M. C., & Finlay, B. B. (2010). Quorum sensing in bacterial virulence. Microbiology, 156, 2271–2282.CrossRefGoogle Scholar
  4. 4.
    Appelbaum, P. C. (2012). 2012 and beyond: Potential for the start of a second pre-antibiotic era. Journal of Antimicrobial Agents and Chemotherapy, 67, 2062–2068.CrossRefGoogle Scholar
  5. 5.
    Asfour, H. Z. (2017). Antiquorum sensing natural compounds. Journal of Microscopy and Ultrastructure.
  6. 6.
    Babapour, E., Haddadi, A., Mirnejad, R., Angaji, S. A., & Amirmozafari, N. (2016). Biofilm formation in clinical isolates of nosocomial Acinetobacter baumannii and its relationship with multidrug resistance. Asian Pacific Journal of Tropical Biomedicine, 6(6), 528–533.CrossRefGoogle Scholar
  7. 7.
    Balaban, N., Cirioni, O., Giacometti, A., Ghiselli, R., Braunstein, J. B., Silvestri, C., Mocchegiani, F., Saba, V., & Scalise, G. (2007). Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrobial Agents and Chemotherapy, 51(6), 2226–2229. Scholar
  8. 8.
    Bjarnsholt, T., Jensen, P. Ø., Jakobsen, T. H., Phipps, R., Nielsen, A. K., Rybtke, M. T., 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(4), e10115. Scholar
  9. 9.
    Brackman, G., & Coenye, T. (2014). Quorum sensing inhibitors as anti-biofilm agents. Current Pharmaceutical Design, 21(1), 5–11. Scholar
  10. 10.
    Chu, W., Liu, Y., Jiang, Y., Zhu, W., & Zhuang, X. (2013). Production of N-acyl Homoserine Lactones and virulence factors of waterborne Aeromonas hydrophila. Indian Journal of Microbiology, 53(3), 264–268.CrossRefGoogle Scholar
  11. 11.
    D’Almeida, R. E., Molina, R. D. I., Viola, C. M., Luciardi, M. C., Penalver, C. N., Bardon, A., & Arena, M. E. (2017). Comparison of seven structurally related coumarins on the inhibition of quorum sensing of Pseudomonas aeruginosa and Chromobacterium violaceum. Bioorganic Chemistry, 73, 37–42.CrossRefGoogle Scholar
  12. 12.
    Decho, A. W., Norman, R. S., & Visscher, P. T. (2010). Quorum sensing in natural environments: Emerging views from microbial mats. Trends in Microbiology, 18(2), 73–80.CrossRefGoogle Scholar
  13. 13.
    Deep, A., Chaudhary, U., & Gupta, V. (2011). Quorum sensing and bacterial pathogenicity: From molecules to disease. Journal of Laboratory Physician, 3(1), 4–11.CrossRefGoogle Scholar
  14. 14.
    El-Hamid, M. I. A. (2016). A new promising target for plant extracts: Inhibition of bacterial quorum sensing. Journal of Molecular Biology and Biotechnology, 1(1), 4.Google Scholar
  15. 15.
    Federle, M. J., & Bassler, B. L. (2003). Interspecies communication in bacteria. The Journal of Clinical Investigation, 112, 1291–1299.CrossRefGoogle Scholar
  16. 16.
    Figueroa, M., Jarmusch, A. K., Raja, H. A., El-Elimat, T., Kavanaugh, J. S., Horswill, A. R., Cooks, R. G., Cech, N. B., & Oberlies, N. H. (2014). Polyhydroxyanthraquinones as quorum sensing inhibitors from the guttates of Penicillium restrictum and their analysis by desorption electrospray ionization mass spectrometry. Journal of Natural Products, 77(6), 1351–1358. Scholar
  17. 17.
    Galloway, W. R. J. D., Hodgkinson, J. T., Bowden, S., Welch, M., & Spring, D. R. (2012). Applications of small molecule activators and inhibitors of quorum sensing in Gram-negative bacteria. Trends in Microbiology, 20(9), 449–458. Scholar
  18. 18.
    Gohar, M., Faegri, K., Perchat, S., Ravnum, S., Økstad, O. A., Gominet, M., Kolstø, A. B., & Lereclus, D. (2008). The PlcR virulence regulon of Bacillus cereus. PLoS One, 3(7), e002793.CrossRefGoogle Scholar
  19. 19.
    Gohar, M., Økstad, O. A., Gilois, N., Sanchis, V., Kolst, A. B., & Lereclus, D. (2002). Two-dimensional electrophoresis analysis of the extracellular proteome of Bacillus cereus reveals the importance of the PlcR regulon. Proteomics, 2(6), 784–791.CrossRefGoogle Scholar
  20. 20.
    Gonzalez, J. E., & Keshavan, N. D. (2006). Messing with bacterial quorum sensing. Microbiology and Molecular Biology Reviews, 70(4), 859–875. Scholar
  21. 21.
    Jimenez, P. N., Koch, G., Thompson, J. A., Xavier, K. B., Cool, R. H., & Quax, W. J. (2012). The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiology and Molecular Biology Reviews, 76(1), 46–65.CrossRefGoogle Scholar
  22. 22.
    Jung, S. A., Chapman, C. A., & Ng, W. L. (2015). Quadruple quorum-sensing inputs control Vibrio cholerae virulence and maintain system robustness. PLoS Pathogens, 11(4), e1004837. Scholar
  23. 23.
    Kalia, V. C. (2013). Quorum sensing inhibitors: An overview. Biotechnology Advances, 31(2), 224–245. Scholar
  24. 24.
    Kalishwaralal, K., Barathmanikanth, S., Pandian, S. R. K., Deepak, V., & Gurunathan, S. (2010). Silver nanoparticles impede the biofilm formation by Pseudomonas aeruginosa and Staphylococcus epidermidis. Colloids and Surfaces B: Biointerfaces, 79, 340–344.CrossRefGoogle Scholar
  25. 25.
    Karminik, A., Baseri-Salehi, M., & Kheirkhah, B. (2017). Pseudomonas aeruginosa quorum sensing modulates immune responses: An updated review article. Immunology Letters, 190, 1–6.CrossRefGoogle Scholar
  26. 26.
    Kavanaugh, J. S., Thoendel, M., & Horswill, A. R. (2007). A role for type I signal peptidase in Staphylococcus aureus quorum sensing. Molecular Microbiology, 65(3), 780–798. Scholar
  27. 27.
    Lasarre, B., & Federle, M. J. (2013). Exploiting quorum sensing to confuse bacterial pathogens. Microbiology and Molecular Biology Reviews, 77(1), 73–111. Scholar
  28. 28.
    Lee, J., Wu, J., Deng, Y., Wang, J., Wang, C., Wang, J., Chang, C., Dong, Y., Williams, P., & Zhang, L. H. (2013). A cell-cell communication signal integrates quorum sensing and stress response. Nature Chemical Biology, 9, 339–343.CrossRefGoogle Scholar
  29. 29.
    Lee, J., & Zhang, L. (2015). The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein & Cell, 6(1), 26–41.CrossRefGoogle Scholar
  30. 30.
    Lereclus, D., Agaisse, H., Gominet, M., Salamitou, S., & Sanchis, V. (1996). Identification of a Bacillus thuringiensis gene that positively regulates transcription of the phosphatidylinositol-specific phospholipase C gene at the onset of the stationary phase. Journal of Bacteriology, 178(10), 2749–2756.CrossRefGoogle Scholar
  31. 31.
    Li, Z., & Nair, S. K. (2012). Quorum sensing: How bacteria can coordinate activity and synchronize their response to external signals? Protein Science, 21, 1403–1417.CrossRefGoogle Scholar
  32. 32.
    Luciardi, M. C., Blazquez, M. A., Cartagena, E., Bardon, A., & Arena, M. E. (2016). Mandarin essential oils inhibit quorum sensing and virulence factors of Pseudomonas aeruginosa. LWT- Food Science and Technology, 68, 373–380.CrossRefGoogle Scholar
  33. 33.
    Matson, J. S., Withey, J. H., & Dirita, V. J. (2007). Regulatory networks controlling Vibrio cholerae virulence gene expression. Infection and Immunity, 75(12), 5542–5549. Scholar
  34. 34.
    McCarthy, R. R., & O’Gara, F. (2015). The impact of phytochemicals present in the dieton microbial signaling in the human gut. Journal of Functional Foods, 14, 684–691.CrossRefGoogle Scholar
  35. 35.
    Miller, M. B., & Bassler, B. L. (2001). Quorum sensing in bacteria. Annual Review in Microbiology, 55, 165–199.CrossRefGoogle Scholar
  36. 36.
    Miller, M. B., Skorupski, K., Lenz, D. H., Taylor, R. K., & Bassler, B. L. (2002). Parallel quorum sensing systems converge to regulate virulence in Vibrio cholera. Cell, 110, 303–314.CrossRefGoogle Scholar
  37. 37.
    Milton, D. L. (2006). Quorum sensing in Vibrios: Complexity for diversification. International Journal of Medical Microbiology, 296(2–3), 61–71. Scholar
  38. 38.
    Mori, Y., Ishikawa, S., Ohnishi, H., Shimatani, M., Morikawa, Y., Hayashi, K., Ohnishi, K., Kiba, A., Kai, K., & Hikichi, Y. (2017). Involvement of ralfuranones in the quorum sensing signalling pathway and virulence of Ralstonia solanacearum strain OE1-1. Molecular Plant Pathology. Scholar
  39. 39.
    Myszka, K., Schmidt, M. T., Majcher, M., Juzwa, W., Olkowicz, M., & Czaczyk, K. (2016). Inhibition of quorum sensing-related biofilm of Pseudomonas fluorescens KM121 by Thymus vulgare essential oil and its major bioactive compounds. International Biodeterioration and Biodegradation, 114, 252–259.CrossRefGoogle Scholar
  40. 40.
    Nazzaro, F., Fratianni, F., & Coppola, R. (2013). Quorum sensing and phytochemicals. International Journal of Molecular Sciences, 14(6), 12607–12619.CrossRefGoogle Scholar
  41. 41.
    Norizan, S. N. M., Yin, W. F., & Chan, K. G. (2013). Caffeine as a potential quorum sensing inhibitor. Sensors, 13, 5117–5129.CrossRefGoogle Scholar
  42. 42.
    O’Loughlin, C. T., Miller, L. C., Siryaporn, A., Drescher, K., Semmelhack, M. F., & Bassler, B. L. (2013). A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proceedings of the National Academy of Sciences, 110(44), 17981–17986. Scholar
  43. 43.
    Okada, M., Nakamura, Y., Hayashi, S., Ozaki, K., & Usami, S. (2015). Chemical structure and biological activity of a quorum sensing pheromone from Bacillus subtilis subsp. natto. Biorganic and Medicinal Chemistry Letters., 25(19), 4293–4296.CrossRefGoogle Scholar
  44. 44.
    Omer Bendori, S., Pollak, S., Hizi, D., & Eldar, A. (2015). The RapP-PhrP quorum-sensing system of Bacillus subtilis strain NCIB3610 affects biofilm formation through multiple targets, due to an atypical signal-insensitive allele of RapP. Journal of Bacteriology, 197(3), 592–602. Scholar
  45. 45.
    Oslizlo, A., Stefanic, P., Dogsa, I., & Mandic-Mulec, I. (2014). Private link between signal and response in Bacillus subtilis quorum sensing. Proceedings of the National Academy of Sciences, 111(4), 1586–1591. Scholar
  46. 46.
    Ouyang, J., Sun, F., Feng, W., Sun, Y., Qiu, X., Xiong, L., Liu, Y., & Chen, Y. (2016). Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa. Journal of Applied Microbiology, 120, 966–974.CrossRefGoogle Scholar
  47. 47.
    Packiavathy, I. A. S. V., Priya, S., Pandian, S. K., & Ravi, A. V. (2014). Inhibition of biofilm development of uropathogens by curcumin – An anti-quorum sensing agent from Curcuma longa. Food Chemistry, 148, 453–460.CrossRefGoogle Scholar
  48. 48.
    Park, H., Lee, K., Yeo, S., Shin, H., & Holzapfel, W. H. (2017). Autoinducer-2 quorum sensing influences viability of Escherichia coli O157:H7 under osmotic and in vitro gastrointestinal stress conditions. Frontiers in Microbiology, 8, 1077.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Quave, C. L., Plano, L. R., & Bennett, B. C. (2011). Quorum sensing inhibitors of Staphylococcus aureus from Italian medicinal plants. Planta Medica, 77(2), 188–195.CrossRefGoogle Scholar
  50. 50.
    Rahman, M. R. T., Lou, Z., Yu, F., Wang, P., & Wang, H. (2017). Anti-quorum sensing and anti-biofilm activity of Amomum tsaoko (Amommum tsao-ko Crevost et Lemarie) on foodborne pathogens. Saudi Journal of Biological Sciences, 24(2), 324–330.CrossRefGoogle Scholar
  51. 51.
    Rajesh, P. S., & Rai, V. R. (2014). Quorum quenching activity in cell-free lysate of endophytic bacteriaisolated from Pterocarpus santalinus Linn., and its effect on quorum sensing regulated biofilm in Pseudomonas aeruginosa PAO1. Microbiological Research, 169, 561–569.CrossRefGoogle Scholar
  52. 52.
    Rasamiravaka, T., Jedrzejowski, A., Kiendrebeogo, M., Rajaonson, S., Randriamampionona, D., Rebemanantsoa, C., Andriantsimahavandy, A., Rasamindrakotroka, A., Duez, P., El Jaziri, M., & Vandeputte, O. M. (2013). Endemic Malagasy Dalbergia species inhibit quorum sensing in Pseudomonas aeruginosa PAO1. Microbiology, 159, 924–938.CrossRefGoogle Scholar
  53. 53.
    Rasmussen, T. B., & Givskov, M. (2006). Quorum-sensing inhibitors as anti-pathogenic drugs. International Journal of Medical Microbiology, 296(2–3), 149–161. Scholar
  54. 54.
    Reading, N. C., & Sperandio, V. (2006). Quorum sensing: The many languages of bacteria. FEMS Microbiology Letters, 254, 1–11.CrossRefGoogle Scholar
  55. 55.
    Rumbaugh, K. P., Diggle, S. P., Watters, C. M., Ross-Gillespie, A., Griffin, A. S., & West, S. A. (2009). Quorum sensing and the social evolution of bacterial virulence. Current Biology, 19, 341–345.CrossRefGoogle Scholar
  56. 56.
    Rutherford, S. T., & Bassler, B. L. (2012). Bacterial quorum sensing: Its role in virulence and possibilities for its control. Cold Spring Harbor Perspectives in Medicine, 2, a012427.CrossRefGoogle Scholar
  57. 57.
    Sakuragi, Y., & Kolter, R. (2007). Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa. Journal of Bacteriology, 189(14), 5383–5386.CrossRefGoogle Scholar
  58. 58.
    Schauder, S., & Bassler, B. L. (2001). The languages of bacteria. Genes and Development, 15, 1468–1480.CrossRefGoogle Scholar
  59. 59.
    Schertzer, J. W., Boulette, M. L., & Whiteley, M. (2009). More than a signal: Non-signaling properties of quorum sensing molecules. Trends in Microbiology, 17(5), 189–195.CrossRefGoogle Scholar
  60. 60.
    Smith, R. S., & Iglewski, B. S. (2003a). P. aeruginosa quorum-sensing systems and virulence. Current Opinion in Microbiology, 6, 56–60.CrossRefGoogle Scholar
  61. 61.
    Smith, R. S., & Iglewski, B. H. (2003b). Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. Journal of Clinical Investigation, 112(10), 1460–1465. Scholar
  62. 62.
    Starkey, M., Lepine, F., Maura, D., Bandyopadhaya, A., Lesic, B., He, J., Kitao, T., Righi, V., Milot, S., Tzika, A., & Rahme, L. (2014). Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity. PLoS One, 10(8), e1004321.Google Scholar
  63. 63.
    Teshler, J. K., Zamorano-Sanchez, D., Utada, A. S., Warner, C. J. A., Wong, G. C. L., Linington, R. G., & Yildiz, F. H. (2015). Living in the matrix: Assembly and control of Vibrio cholerae biofilms. Nature Reviews Microbiology, 13, 255–268.CrossRefGoogle Scholar
  64. 64.
    Vendeville, A., Winzer, K., Heurlier, K., Tang, C. M., & Hardie, K. R. (2005). Making “sense” of metabolism: Autoinducer-2, LUXS and pathogenic bacteria. Nature Reviews Microbiology, 3(5), 383–396. Scholar
  65. 65.
    Wang, H., Tu, F., Gui, Z., Lu, X., & Chu, W. (2013). Antibiotic resistance profiles and quorum sensing-dependent virulence factors in clinical isolates of Pseudomonas aeruginosa. Indian Journal of Microbiology, 53(2), 163–167.CrossRefGoogle Scholar
  66. 66.
    Waters, C. M., & Bassler, B. L. (2005). Quorum sensing: Cell-to-cell communication in bacteria. Annual Review in Cell and Developmental Biology, 21, 319–346.CrossRefGoogle Scholar
  67. 67.
    West, S. A., Winzer, K., Gardner, A., & Diggle, S. P. (2012). Qurom sensing and the confusion about diffusion. Trends in Microbiology, 20(12), 586–594.CrossRefGoogle Scholar
  68. 68.
    Whiteley, M., Diggle, S. P., & Greenberg, E. P. (2017). Progress in and promise of bacterial quorum sensing research. Nature, 551, 313–320.CrossRefGoogle Scholar
  69. 69.
    Williams, P., & Camara, M. (2009). Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: A tale of regulatory networks and multifunctional signal molecules. Current Opinion in Microbiology, 12, 182–191.CrossRefGoogle Scholar
  70. 70.
    Williams, P. (2007). Quorum sensing, communication and cross-kingdom signalling in the bacterial world. Microbiology, 153, 3923–3938.CrossRefGoogle Scholar
  71. 71.
    Winzer, K., & Williams, P. (2001). Quorum sensing and the regulation of virulence gene expression in pathogenic bacteria. International Journal of Medical Microbiology, 291, 131–143.CrossRefGoogle Scholar
  72. 72.
    Wynendaele, E., Pauwels, E., Van de Wiele, C., Burvenich, C., & De Spiegeleer, B. (2012). The potential role of quorum-sensing peptides in oncology. Medical Hypotheses, 78, 814–817.CrossRefGoogle Scholar
  73. 73.
    Yang, S., Abdel-Razek, O. A., Cheng, F., Bandyopadhyay, D., Shetye, G. S., Wang, G., & Luk, Y. Y. (2014). Bicyclic brominated furanones: A new class of quorum sensing modulators that inhibit bacterial biofilm formation. Bioorganic and Medicinal Chemistry, 22, 1313–1317.CrossRefGoogle Scholar
  74. 74.
    Zhu, J., Miller, M. B., Vance, R. E., Dziejman, M., Bassler, B. L., & Mekalanos, J. J. (2002). Quorum-sensing regulatorscontrol virulence gene expression in Vibrio cholerae. Proceedings of the National Academy of Sciences, 99(5), 3129–3134.CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Parasuraman Paramanantham
    • 1
  • Subhaswaraj Pattnaik
    • 1
  • Siddhardha Busi
    • 1
  1. 1.Department of Microbiology, School of Life SciencesPondicherry UniversityPuducherryIndia

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