Quorum Sensing in Vibrio fischeri Quorum Sensing (QS) is a type of bacterial cell-to-cell communication, which enables a single cell to sense the number (concentration) of bacteria within a population. QS is achieved through the production, release and detection of special signaling molecules called autoinducers. Each cell produces autoinducer molecules and releases them into the environment. By continuously monitoring the concentration of these molecules in the environment each cell can sense the number of bacteria in the population. Many bacterial systems with QS behavior have been discovered and studied. The marine bioluminescent bacteria Vibrio fischeri is one such interesting and well-studied system. The V.fischeri bacterium exists in a free-living state or as a symbiont of certain luminescent fish or squid. The bacteria luminesce only when present in large concentrations and do not emit light when in the free-living state. Research into the regulatory mechanism of bioluminescence in these bacteria led to the discovery of QS behavior in the system. The luminescence genes turn on only when the cell density is high. QS in V.fischeri relies on the synthesis, release and subsequent sensing of a signal molecule (autoinducer) known as N-acyl homserine lactone (AHL). AHL is synthesized by the protein LuxI and sensed by the protein LuxR. When cell density is low, concentration of AHL in the surrounding area is low. As cell density increases, concentration of AHL increases. When the AHL in the environment reaches a specific threshold concentration, it interacts with the LuxR protein to form a complex. The LuxR-AHL complex then causes the luminescence genes to be switched on. This complex also causes AHL to be produced in large quantities than before. Thus, the AHL is able to autoinduce its own synthesis. There is a vast amount of experimental literature available about this system. Efforts to model the QS behavior in this system are mostly based on differential equations. Few authors have also adopted a hybrid modeling approach. This is a very interesting system to study and I will delve into the details of the existing modeling approaches and key biological findings over the next week. Given below is a list of references which seemed relevant at first glance. Bibliography: 1. Belta, C., Schug, J., Dang, T., Kumar, V., Pappas, G. J., Rubin, H. and Dunlap, P. V. (2001) Stability and reachability analysis of a hybrid model of luminescence in the marine bacterium V.fischeri. Grasp lab, University of Pennsylvania, Philadelphia, PA. 2. Brookfield, J. F. Y. (1998) Quorum Sensing and Group Selection. Evolution. 52, 1263-1269. 1
3. Brown, S. P. and Johnstone, R. A. (2001) Cooperation in the dark: signalling and collective action in quorum-sensing bacteria. Proc. R. Soc. Lond. B, 268, 961-965. 4. Callahan, S. M., Dunlap, P. V. (2000) LuxR and acyl-homoserine-lactonecontrolled non-lux genes define a quorum-sensing regulon in Vibrio fischeri. J. Bacteriol., 182, 2811-2822. 5. Davies, D. G., Parsek, M. R., Pearson, J. P. Iglewski, B. H. Costerton, J. W. and Greenberg, E. P. (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science. 280 295-298 6. Dockery, J.D. and Keener, J.P. (2001) A mathematical model for quorum sensing in Pseudomonas aeruginosa. Bull. Math. Biol., 63, 95-116. 7. Dunlap, P. V. and Kuo, A. (1992) Cell density-dependent modulation pf the Vibrio fischeri luminescence system in the absence of autoinducer and LuxR protein. J. Bacteriol. 174(8), 2440-2448. 8. Dunlap, P. V. (2000) Quorum regulation of luminescence in Vibrio fischeri. In D. Bartlett (ed), Mol. Marine Microbial. Horizon Press, Norfolk, UK, 3-21 9. Engebrecht, J., Nealson, K. and Silverman, M. (1983) Bacterial bioluminescence: Isolation and genetic analysis of functions from Vibrio fischeri. Cell 32, 773-781. 10. Engebrecht, J. and Silverman, M. (1986) Regulation of expression of bacterial genes for bioluminescence. In Genetic engineering Setlow, J.K. and Hollaender, A (eds), Plenum, New York, 31-44. 11. Fuqua, C., Parsek, M. R. & Greenberg, E. P. (2001) Regulation of gene expression by cell-to-cell communication: Acyl homoserine lactone quorum sensing. Annu. Rev. Genet. 35, 439-468. 12. Fuqua, C., Winans, S. C. & Greenberg, E. P. (1996). Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu. Rev. Microbiol. 50, 727-751. 13. Gray, K.M., Passador, L., Iglewski, B.H. and Greenberg, E.P. (1994) Interchangeability and specificity of components from the quorum-sensing regulatory systems of Vibrio fischeri and Pseudomonas aeruginosa. J. Bacteriol. 176, 3076-3080. 14. James, S., Nilsson, P., James, G., Kjelleberg, S. and Fagerstrom, T. (2000) Luminescence control in the marine bacterium Vibrio fischeri: An analysis of the dynamics of lux regulation. J. Mol. Biol. Academic Press. 296, 1127-1137. 15. Kaiser, D. and Losick, R. (1993) How and why bacteria talk to each other. Cell, 73, 873-885 2
16. Kaplan, H.B. and Greenberg, E.P. (1987) Overproduction and purification of the luxr gene product: Transcriptional activator of the Vibrio fischeri luminescence system. Proc. Natl. Acad. Sci. USA 84, 6639-6643. 17. Kuo, A., Blough, N.V. and Dunlap, P.V. (1994) Multiple N-acyl-homoserine lactone autoinducers of luminescence in the marine symbiotic bacterium Vibrio fischeri. J. Bacteriol. 176, 7588-7565. 18. Kuo, A., Callahan, S.M. and Dunlap, P.V. (1996) Modulation of luminescence operon expression by N-octanoyl-L-homoserine lactone in ains mutants of Vibrio fischeri. J. Bacteriol. 178, 971-976. 19. Meighen, E.A. (1994) Genetics of bacterial bioluminescence. Annu. Rev. Genet. 28, 117-139. 20. Miller, M. B. and Bassler, B. L. (2001) Quorum sensing in Bacteria. Annu. Rev. Microbiol. 55, 165-199. 21. Miyamoto, C.M., Lin, Y.H. and Meighen, E.A. (2000) Control of bioluminescence in Vibrio fischeri by the LuxO signal response regulator. Mol. Microbiol. 36, 594-607. 22. Pearson, J. P. (2002) Early activation of quorum sensing. J. Bacteriol., 184, 2569-2571. 23. Picioreanu, C., van Loosdrecht, M.C.M, Heijnen, J.J. (1998) Mathematical modelling of biofilm structure with a hybrid differential-discrete cellular automaton approach. Biotech. Bioeng., 58, 101-116. 24. Picioreanu, C., van Loosdrecht, M.C.M, Heijnen, J.J. (1998) A new combined differential discrete cellular automaton approach for biofilm modelling: application for growth in gel beds. Biotech. Bioeng., 57, 718-731. 25. Pritchett, L.A., Dockery, J.D. (2001) Steady state solutions of a 1 dimensional biofilm model. Math. Comput. Model., 33, 255-263. 26. Rittmann, B.E., Manem, J.A. (1992) Development and experimental evaluation of a steadystate, multispecies biofilm model. Biotech. Bioeng., 39, 914-922. 27. Ruby, E.G. (1996) Lessons from a cooperative,bacterial-animal association: The Vibrio fischeri Euprymna Scolopes Light organ symbiosis. Annu. Rev. Microbiol. 50, 591-624. 28. Ruby, E.G. and Nealson, K.H. (1976) Symbiotic association of Photobacterium fischeri with the marine luminous fish Monocentris japonica: A model of symbiosis based on bacterial studies. Biol. Bull. 151, 574-586. 3
29. Ruby, E. G. & McFall-Ngai, M. J. (1992). A squid that glows in the night: development of an animal-bacterial mutualism. J. Bacteriol. 174, 4865-4870. 30. Salmond, G.P.C., Bycroft, B.W., Stewart, G.S.A.B. and Williams, P. (1995) The bacterial enigma : Cracking the code of cell-cell communication. Mol. Microbiol. 16, 615-624 31. Schaefer, A.L., Hanzelka, B.L., Eberhard, A. and Greenberg, E.P. (1996) Quorum sensing in Vibrio fischeri: probing autoinducer-luxr interactions with autoinducer analogs. J. Bacteriol. 178, 2897-2901. 32. Schaefer, A.L., Val, D.L., Hanzelka, B.L., Cronan, J.E. and Greenberg, E.P. (1996) Generation of cell-to-cell signals in quorum sensing: Acyl homoserine lactone synthase activity of a purified Vibrio fischeri LuxI protein. Proc. Natl. Acad. Sci. USA 93, 9505-9509. 33. Shadel, G.S. and Baldwin, T.O. (1991) The Vibrio fischeri LuxR protein is capable of bidirectional stimulation of transcription and both positive and negative regulation of the luxr gene. J. Bacteriol. 173, 568-574. 34. Shadel, G.S. and Baldwin, T.O. (1992) Positive autoregulation of the Vibrio fischeri luxr gene. J. Biol. Chem. 267, 7696-7702. 35. Shapiro, J.A. (1998) Thinking of bacteria as multicellular organisms. Annu. Rev. Microbiol. 52, 81-104 36. Sitnikov, D.M., Schineller, J.B. and Baldwin, T.O. (1995) Transcriptional regulation of bioluminescence genes from Vibrio fischeri. Mol. Microbiol. 17, 801-812 37. Stevens, A.M. and Greenberg, E.P. (1997) Quorum sensing in Vibrio fischeri: Essential elements for activation of the luminescence genes. J. Bacteriol. 179, 557-562. 38. Ulitzur, S. and Dunlap, P. V. (1995) Regulatory circuitry controlling luminescence autoinduction in Vibrio fischeri. Photochem. Photobiol. 62, 625-632. 39. Ulitzur, S. and Kuhn, J. (1988) The transcription of bacterial luminescence is regulated by sigma 32. J. Biolumin. Chemilumin. 2, 81-93. 40. Ulitzur, S. (1989) The regulatory control of the bacterial luminescence system a new view. J. Biolumin. Chemilumin. 4, 317-325. 41. Visick, K.L., Foster, J., Doino, J., McFall-Ngai, M.J. and Ruby, E.G. (2000) Vibrio fischeri lux play an important role in colonization and development of the host light organ. J. Bacteriol. 182, 4578-4586. 4
42. Visick, K.L. and McFall-Ngai, M.J. (2000) An exclusive contract: specificity in the Vibrio fischeri-eupymna scolopes partership. J. Bacteriol. 182, 1779-1787 43. Wanner, O., Gujer, W. (1986) A multispecies biofilm model. Biotech. Bioeng., 28, 314-328. 44. Wanner, O., Reichert, P. (1995) Mathematical modelling of mixed-culture biofilms. Biotech. Bioeng., 49, 172-184. 45. Ward, J.P., King, J.R., Koerber, A.J., Williams, P., Croft, J.M., Sockett, R.E. (2001) Mathematical model of quorum sensing in bacteria. IMA J. Math. Appl. Med. Biol., 18, 263-292. 5