Functionality of Autoinducer Systems in Complex Environments

Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Cell-to-cell signalling via small diffusible molecules, usually termed quorum sensing (QS), represents a common behaviour in bacteria. This signalling regulates life style switches in many, if not most symbiotic microbial species either beneficial or pathogenic for their eukaryotic hosts, but is also involved in controlling environmental processes such as biofouling, degradation processes in sewage plants or environmental pollutions and N cycling [1–4]. Biochemically, the core of a generic system comprises a cytoplasmatic signal synthase (or several involved enzymes), a small, diffusible signal which is released into the environment, and a signal receptor located in the cell membrane or in the cytoplasma. The signal-receptor complex directly or indirectly controls the expression of target genes (Fig. 5.1). The signal was termed autoinducer (AI), because the same cells produce and react on the signal molecules. For an overview of the various chemical realizations of AI systems see, e.g. Atkinson and Williams [5]. Originally, three main types of AI molecules have been described: (a) Mainly gram-negative proteobacteria, but also some cyanobacteria and archaebacteria employ molecules of the acylhomoserine lactone (AHL) group as AIs, (b) oligopeptide AIs occur in gram-positive bacteria, and (c) AI2 has been described as a universal signal for interspecies communication. Recently, a still increasing number of AIs belonging to various chemical classes have been discovered.


Quorum Sense Push Factor Acylhomoserine Lactone Regulation Architecture Nutrient Influence 



We thank Martin Schuster for the fruitful discussion of our article.


  1. 1.
    Valle A, Bailey MJ, Whiteley AS, Manefield M (2004) N-acyl-l-homoserine lactones (AHLs) affect microbial community composition and function in activated sludge. Environ Microbiol 6:424–433CrossRefGoogle Scholar
  2. 2.
    Antunes LCM, Ferreira RBR, Buckner MMC, Finlay BB (2010) Quorum sensing in bacterial virulence. Microbiology 156:2271–2282CrossRefGoogle Scholar
  3. 3.
    De Clippeleir H, Defoirdt T, Vanhaecke L, Vlaeminck SE, Carballa M, Verstraete W, Bonn N (2011) Long-chain acylhomoserine lactones increase the anoxic ammonium oxidation rate in an OLAND biofilm. Appl Microbiol Biotechnol 90:1511–1519CrossRefGoogle Scholar
  4. 4.
    Shrout JD, Nerenberg R (2012) Monitoring bacterial twitter: Does quorum sensing determine the behaviour of water and wastewater treatment biofilms? Environ Sci Technol 46:1995–2005CrossRefADSGoogle Scholar
  5. 5.
    Atkinson S, Williams P (2009) Quorum sensing and social networking in the microbial world. J R Soc Interface 6:959–978CrossRefGoogle Scholar
  6. 6.
    Goryachev AB (2009) Design principles of the bacterial quorum sensing gene networks. WIREs Syst Biol Med 1:45–60Google Scholar
  7. 7.
    Ulitzur S (1989) The regulatory control of the bacterial luminescence system—a new view. J Biolumin Chemilumin 4:317–325CrossRefGoogle Scholar
  8. 8.
    Goryachev AB (2011) Understanding bacterial cell–cell communication with computational modeling. Chem Rev 111:238–250CrossRefGoogle Scholar
  9. 9.
    Winzer K, Hardie KR, Williams P (2002) Bacterial cell-to-cell communication: sorry, can’t talk now—gone to lunch! Curr Opin Microbiol 5:216–222CrossRefGoogle Scholar
  10. 10.
    Diggle SP, Gardner A, West S, Griffin AS (2007) Evolutionary theory of bacterial quorum sensing: when is a signal not a signal? Phil Trans R Soc Lond B 362:1241–1249Google Scholar
  11. 11.
    Diggle SP, Griffin AS, Campbell GS, West SA (2007) Cooperation and conflict in quorum-sensing bacterial populations. Nature 450:411–414CrossRefADSGoogle Scholar
  12. 12.
    Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199CrossRefGoogle Scholar
  13. 13.
    Whitehead NA, Barnard AML, Slater H, Simpson NJL, Salmond GPC (2001) Quorum-sensing in gram-negative bacteria. FEMS Microbiol Rev 25:65–404CrossRefGoogle Scholar
  14. 14.
    Platt TG, Fuqua C (2010) What’s in a name? The semantics of quorum sensing. Trends Microbiol 18:383–387CrossRefGoogle Scholar
  15. 15.
    Shompole S, Henon KT, Liou LE, Dziewanowska K, Bohach GA, Bayles KW (2003) Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing. Mol Microbiol 49:919–927CrossRefGoogle Scholar
  16. 16.
    Kirisits MJ, Margolis JJ, Purevdorj-Gage BL, Vaughan B, Chopp DL, Stoodley P, Parsek MR (2007) Influence of the hydrodynamic environment on quorum sensing in Pseudomonas aeruginosa biofilms. J Bacteriol 189:8357–8360CrossRefGoogle Scholar
  17. 17.
    Dulla G, Lindow SE (2008) Quorum size of Pseudomonas syringae is small and dictated by water availability on the leaf surface. Proc Natl Acad Sci U S A 105:3082–3087CrossRefADSGoogle Scholar
  18. 18.
    Carnes EC, Lopez DM, Donegan NP, Cheung A, Gresham H, Timmins GS, Brinker CJ (2010) Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria. Nat Chem Biol 6:41–45CrossRefGoogle Scholar
  19. 19.
    Meyer A, Megerle JA, Kuttler C, Müller J, Aguilar C, Eberl L, Hense BA, Rädler JO (2012) Dynamics of AHL mediated quorum sensing under flow and non-flow conditions. Phys Biol 9:026007. doi: 10.1088/1478-3975/9/2/026007 CrossRefADSGoogle Scholar
  20. 20.
    Hense BA, Kuttler C, Müller J, Rothballer M, Hartmann A, Kreft J-U (2007) Does efficiency sensing unify diffusion and quorum sensing? Nat Rev Microbiol 5:230–239CrossRefGoogle Scholar
  21. 21.
    Connell JL, Wessel AK, Parsek MR, Ellington AD, Whiteley M, Shear JB (2010) Probing prokaryotic social behaviors with bacterial “lobster traps”. MBIO 1:e00202–e00210. doi: 10.1128/mBio.00202-10 CrossRefGoogle Scholar
  22. 22.
    Whitaker RD, Pember S, Wallace BC, Brodley CE, Walt DR (2011) Single cell time-resolved quorum responses reveal dependence on cell density and configuration. J Biol Chem 286:21623–21632CrossRefGoogle Scholar
  23. 23.
    Alberghini S, Polone E, Corich V, Carlot M, Seno F, Trovato A, Squartini A (2009) Consequences of relative cellular positioning on quorum sensing and bacterial cell-to-cell communication. FEMS Microbial Lett 292:149–161CrossRefGoogle Scholar
  24. 24.
    Schuster M, Lostroh CP, Ogi T, Greenberg EP (2003) Identification, timing, and signal specifity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol 185:2066–2079CrossRefGoogle Scholar
  25. 25.
    Willcox MDP, Zhu H, Conibear TCR, Hume EBH, Givskov M, Kjelleberg S, Rice SA (2008) Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis. Microbiology 154:2184–2194CrossRefGoogle Scholar
  26. 26.
    Coggan KA, Wolfgang MC (2012) Global regulatory pathways and cross-talk control Pseudomonas aeruginosa environmental lifestyle and virulence phenotype. Curr Issues Mol Biol 14:47–69Google Scholar
  27. 27.
    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 4:400–409CrossRefGoogle Scholar
  28. 28.
    Hassett DJ, Ma JF, Elkins JG, Ochsner UA, West SEH, Huang C-T (1999) Control of catalase and superoxide dismutase by quorum sensing in Pseudomonas aeruginosa: catalase is important is resistance of biofilm organisms to hydrogen peroxide. Mol Microbiol 34: 1082–1093CrossRefGoogle Scholar
  29. 29.
    Pontes MH, Babst MH, Lochhead R, Oakeson K, Smith K, Dale C (2008) Quorum sensing primes the oxidative stress response in the insect endosymbiont, Sodalis glossinidius. PLoS One 3:e3541CrossRefADSGoogle Scholar
  30. 30.
    Studer SV, Mandel MJ, Ruby EG (2008) AinS quorum sensing regulates the Vibrio fischeri acetate switch. J Bacteriol 190:5915–5923CrossRefGoogle Scholar
  31. 31.
    Pierson LS III, Pierson EA (2010) Metabolism and function of phenazines in bacteria: impacts on the behaviour of bacteria in the environment and biotechnological processes. Appl Microbiol Biotechnol 86:1659–1670CrossRefGoogle Scholar
  32. 32.
    Poinar GO, Thomas G, Haygood M, Nealson KH (1980) Growth and luminescence of the symbiotic bacteria associated with the terrestrial nematode, Heterorhabditis bacteriophora. Soil Biol Biochem 12:5–10CrossRefGoogle Scholar
  33. 33.
    Diggles BK, Moss MA, Carson J, Anderson CD (2000) Luminous vibriosis in rock lobster Jasus verreauxi (Decapoda: Palinuridae) phyllosoma larvae associated with infection by Vibrio harveyi. Dis Aquat Organ 43:127–137CrossRefGoogle Scholar
  34. 34.
    Dunlap PV, Kita-Tsukamoto K (2006) Luminous bacteria, 3rd ed., vol 2, The prokaryotes: a handbook on the biology of bacteria. Springer, New York, pp 863–892. doi: 10.1007/0-387-30742-7_27
  35. 35.
    Krin E, Chakroun N, Turlin E, Givaudan A, Gaboriau F, Bonne I et al (2006) Pleiotropic role of quorum-sensing autoinducer AI-2 in Photorhabdus luminescens. Appl Environ Microbiol 72:6439–6451CrossRefGoogle Scholar
  36. 36.
    Münch A, Stingl L, Jung K, Heermann R (2008) Photorhabdus luminescens genes induced upon insect infection. BMC Genomics 9:1–17CrossRefGoogle Scholar
  37. 37.
    McElroy WD, Seliger HH (1962) Origin and evolution of bioluminescence. In: Kasha M, Pullman B (eds) Horizons in biochemistry. Academic, New York, pp 91–101Google Scholar
  38. 38.
    Timmins GS, Jackson SK, Swartz HM (2001) The evolution of bioluminescent oxygen consumption as an ancient oxygen detoxification mechanism. J Mol Evol 52:321–332Google Scholar
  39. 39.
    Szpilewska H, Czyz A, Wegrzyn G (2003) Experimental evidence for the physiological role of bacterial luciferase in the protection of cells against oxidative stress. Curr Microbiol 47: 379–382CrossRefGoogle Scholar
  40. 40.
    Lyzen R, Wegrzyn G (2005) Sensitivity of dark mutants of various strains of luminescent bacteria to reactive oxygen species. Arch Microbiol 183:203–208CrossRefGoogle Scholar
  41. 41.
    Müller J, Hense BA. Efficiency sensing of colonies and environmental engineering, in preparationGoogle Scholar
  42. 42.
    Chopp D, Kiritis M, Moran B, Parsek M (2002) A mathematical model of quorum sensing in a growing bacterial biofilm. J Ind Microbiol Biotechnol 29:339–346CrossRefGoogle Scholar
  43. 43.
    Goryachev A, Toh D, Wee K, Lee T, Zhang H, Zhang L (2005) Transition to quorum sensing in an Agrobacterium population: a stochastic model. PLoS Comput Biol 1:45–60. doi: 10.1371/journal.pcbi.0010037 CrossRefADSGoogle Scholar
  44. 44.
    Ulitzur S, Dunlap PV (1995) Regulatory circuitry controlling luminescence autoinduction in Vibrio fischeri. Photochem Photobiol 62:625–632CrossRefGoogle Scholar
  45. 45.
    Dunlap PV (1999) Quorum regulation of bioluminescence in Vibrio fischeri. J Mol Microbiol Biotechnol 1:5–12Google Scholar
  46. 46.
    Chatterjee J, Miyamoto CM, Zouzoulas A, Lang BF, Skouris N, Meighen EA (2002) MetR and CRP bind to Vibrio harveyi lux promotors and regulate luminescence. Mol Microbiol 46: 101–111CrossRefGoogle Scholar
  47. 47.
    De Lay N, Gottesman S (2009) The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behaviour. J Bacteriol 191:461–476CrossRefGoogle Scholar
  48. 48.
    Mellbye B, Schuster M (2014) A physiological framework for the regulation of quorum-sensing-dependent public goods in Pseudomonas aeruginosa. J Bacteriol 196:1155–1164CrossRefGoogle Scholar
  49. 49.
    Hense BA, Müller J, Kuttler C, Hartmann A (2012) Spatial heterogeneity of autoinducer regulation systems. Sensors 12:4156–4171CrossRefGoogle Scholar
  50. 50.
    Holmgren M, Schefer M (2010) Strong facilitation in mild environments: the stress gradient hypothesis revisited. J Ecol 98:1269–1275CrossRefGoogle Scholar
  51. 51.
    Boyer M, Wisniewski-Dye F (2009) Cell-cell signalling in bacteria: not simply a matter of quorum. FEMS Micobiol Ecol 70:1–19CrossRefGoogle Scholar
  52. 52.
    Olhager J, Östlund B (2009) An integrated push–pull manufacturing strategy. Eur J Oper Res 45:135–142CrossRefGoogle Scholar
  53. 53.
    Van Delden C, Comte R, Bally M (2001) Stringent response activates quorum sensing and modulates cell density dependent gene expression in Pseudomonas aeruginosa. J Bacteriol 183:5376–6384CrossRefGoogle Scholar
  54. 54.
    Hedge M, Wood TK, Jayaraman A (2009) The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the las quorum sensing pathway. Appl Microbiol Biotechnol 84:763–776CrossRefGoogle Scholar
  55. 55.
    Newton JA, Fray RG (2004) Integration of environmental and host-derived signals with quorum sensing during plant-microbe interactions. Cell Microbiol 6:213–224CrossRefGoogle Scholar
  56. 56.
    Perez-Montano F, Guasch-Vidal B, Gonzalez-Barroso S, Lopez-Baena FJ, Cubo T, Ollero FJ, Gil-Serrano AM, Rodriguez-Carvajal MA, Bellogin RA, Espuny MR (2011) Nodulation-gene-inducing flavonoids increase overall production of autoinducers and expression of N-acyl homoserine lactone synthesis genes in rhizobia. Res Microbiol 164:749–760CrossRefGoogle Scholar
  57. 57.
    Kaiser D (1986) Control of multicellular development: Dictyostelium and Myxococcus. Ann Rev Genet 20:539–566CrossRefGoogle Scholar
  58. 58.
    Kreft JU (2004) Conflicts of interest in biofilms. Biofilms 1:265–276CrossRefGoogle Scholar
  59. 59.
    Jacob E, Shapira Y, Tauber A (2006) Seeking the foundations of cognition in bacteria: from Schroedinger’s negative entropy to latent information. Physica A 369:495–524CrossRefGoogle Scholar
  60. 60.
    De Kievit T, Gillis R, Marx S, Brown C, Iglewski B (2001) Quorum sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl Environ Microbiol 67:1865–1873CrossRefGoogle Scholar
  61. 61.
    Lenz A, Williamson K, Pitts B, Stewart P, Franklin M (2008) Localized gene expression in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 74:4463–4471CrossRefGoogle Scholar
  62. 62.
    Perez-Osorio A, Williamson K, Franklin M (2010) Heterogeneous rpoS and rhlR mRNA levels and 16S rRNA/rDNA (rRNA gene) ratios within Pseudomonas aeruginosa biofilms, sampled by laser capture microdissection. J Bacteriol 192:2991–3000CrossRefGoogle Scholar
  63. 63.
    Uecker H, Mueller J, Hense BA (2014) Individual-based model for quorum sensing with background flow. Bull Math Biol. doi: 10.1007/s11538-014-9974-2
  64. 64.
    Drescher K, Nadell CD, Stone HA, Wingreen NS, Bassler BL (2014) Solutions to the public goods dilemma in bacterial biofilms. Curr Biol 24:50–55CrossRefGoogle Scholar
  65. 65.
    Chuang JS, Rivoire O, Leibler S (2009) Simpson’s paradox in a synthetic microbial system. Science 323:272–275CrossRefGoogle Scholar
  66. 66.
    Müller J, Kuttler C, Hense BA, Rothballer M, Hartmann A (2006) Cell–cell communication by quorum sensing and dimension–reduction. J Math Biol 53:672–702MathSciNetCrossRefMATHGoogle Scholar
  67. 67.
    Fekete A, Kuttler C, Rothballer M, Hense BA, Fischer D, Buddrus-Schiemann K, Lucio M, Müller J, Schmitt-Kopplin P, Hartmann A (2010) Dynamic regulation of N-acyl-homoserine lactone production and degradation in Pseudomonas putida IsoF. FEMS Microbiol Ecol 72: 22–34CrossRefGoogle Scholar
  68. 68.
    Englmann M, Fekete A, Kuttler C, Frommberger M, Li X, Gebefügi I, Fekete J, Schmitt-Kopplin P (2007) The hydrolysis of unsubstituted N-acylhomoserine lactones to their homoserine metabolites. Analytical approaches using ultra performance liquid chromatography. J Chromatogr A 1160:184–193CrossRefGoogle Scholar
  69. 69.
    LaSarre B, Federle MJ (2013) Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 77:73–111CrossRefGoogle Scholar
  70. 70.
    Cooley M, Chhabra SR, Williams P (2008) N-acylhomoserine lactone-mediated quorum sensing: a twist in the tail and a blow for host immunity. Chem Biol 15:1141–1147CrossRefGoogle Scholar
  71. 71.
    Charlton TS, de Nys R, Netting A, Kumar N, Hentzer M, Givskov M, Kjelleberg S (2000) A novel and sensitive method for the quantification of N-3-oxoacyl homoserine lactones using gas chromatography–mass spectrometry: application to a model bacterial biofilm. Environ Microbiol 2:530–541CrossRefGoogle Scholar
  72. 72.
    Bernatowicz R, Binder T, Noessner E, Rothballer M, Perez-Velazquez J, Hense BA, Kuttler C, Griese M, Eickelberg O, Hartmann A, Krauss-Etschmann S. 3oxoC12-Homoserine lactone from P. aeruginosa impairs multiple human dendritic cell functions required for priming of T cells. J ImmunGoogle Scholar
  73. 73.
    Swearingen MC, Sabag-Daigle A, Ahmer BMM (2013) Are there acyl-homoserine lactones within mammalian intestines? J Bacteriol 195:173–179CrossRefGoogle Scholar
  74. 74.
    Hassett DJ, Sutton MD, Schurr MJ, Herr AB, Caldwell CC, Matu JO (2009) Pseudomonas aeruginosa hypoxic or anaerobic biofilm infection within cystic fibrosis airways. Trends Microbiol 17:1130–1138CrossRefGoogle Scholar
  75. 75.
    Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer KC et al (2002) Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 109:317–325CrossRefGoogle Scholar
  76. 76.
    Hobbie, R.K.: Intermediate Physics for Medicine and Biology, 2nd ed. Wiley Sons, Incorporated, John, 1988, p. 624.Google Scholar
  77. 77.
    Hense, B.A. and Schuster, M.; Unifying principles of microbial autoinducer systems, submittedGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Helmholtz Zentrum München, Institute of Computational BiologyNeuherberg/MunichGermany
  2. 2.Technical University München, Centre for Mathematical SciencesGarchingGermany

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