Abstract
Many unicellular microorganisms use small signaling molecules to determine their local concentration. The processes involved in the production and recognition of these signals are collectively known as quorum sensing (QS). This form of cell–cell communication is used by unicellular microorganisms to co-ordinate their activities, which allows them to function as multi-cellular systems. Recently, several groups have demonstrated artificial intra-species and inter-species communication through synthetic circuits which incorporate components of bacterial QS systems. Engineered QS-based circuits have a wide range of applications such as production of biochemicals, tissue engineering, and mixed-species fermentations. They are also highly useful in designing microbial biosensors to identify bacterial species present in the environment and within living organisms. In this review, we first provide an overview of bacterial QS systems and the mechanisms developed by bacteria and higher organisms to obstruct QS communications. Next, we describe the different ways in which researchers have designed QS-based circuits and their applications in biotechnology. Finally, disruption of quorum sensing is discussed as a viable strategy for preventing the formation of harmful biofilms in membrane bioreactors and marine transportation.
Similar content being viewed by others
References
Anderson JC, Clarke EJ, Arkin AP, Voigt CA (2006) Environmentally controlled invasion of cancer cells by engineered bacteria. J Mol Biol 355:619–627
Atkinson S, Williams P (2009) Quorum sensing and social networking in the microbial world. J R Soc Interface 6:959–978
Balagadde FK, Song H, Ozaki J, Collins CH, Barnet M, Arnold FH, Quake SR, You L (2008) A synthetic Escherichia coli predator–prey ecosystem. Mol Syst Biol 4:187
Bassler BL, Losick R (2006) Bacterially speaking. Cell 125:237–246
Basu S, Mehreja R, Thiberge S, Chen MT, Weiss R (2004) Spatiotemporal control of gene expression with pulse-generating networks. Proc Natl Acad Sci USA 101:6355–6360
Basu S, Gerchman Y, Collins CH, Arnold FH, Weiss R (2005) A synthetic multicellular system for programmed pattern formation. Nature 434:1130–1134
Bjarnsholt T, Givskov M (2007) Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philos Trans R Soc Lond B Biol Sci 362:1213–1222
Boedicker JQ, Vincent ME, Ismagilov RF (2009) Microfluidic confinement of single cells of bacteria in small volumes initiates high-density behavior of quorum sensing and growth and reveals its variability. Angew Chem Int Ed Engl 48:5908–5911
Brenner K, Karig DK, Weiss R, Arnold FH (2007) Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium. Proc Natl Acad Sci USA 104:17300–17304
Brenner K, You L, Arnold FH (2008) Engineering microbial consortia: a new frontier in synthetic biology. Trends Biotechnol 26:483–489
Bulter T, Lee SG, Wong WW, Fung E, Connor MR, Liao JC (2004) Design of artificial cell–cell communication using gene and metabolic networks. Proc Natl Acad Sci USA 101:2299–2304
Carnes EC, Lopez DM, Donegan NP, Cheung A, Gresham H, Timmins GS, Brinker CJ (2009) Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria. Nat Chem Biol 6:41–45
Cha C, Gao P, Chen YC, Shaw PD, Farrand SK (1998) Production of acyl-homoserine lactone quorum-sensing signals by gram-negative plant-associated bacteria. Mol Plant Microbe Interact 11:1119–1129
Chen MT, Weiss R (2005) Artificial cell–cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nat Biotechnol 23:1551–1555
Chowdhary PK, Keshavan N, Nguyen HQ, Peterson JA, Gonzalez JE, Haines DC (2007) Bacillus megaterium CYP102A1 oxidation of acyl homoserine lactones and acyl homoserines. Biochemistry 46:14429–14437
Czajkowski R, Jafra S (2009) Quenching of acyl-homoserine lactone-dependent quorum sensing by enzymatic disruption of signal molecules. Acta Biochim Pol 56:1–16
de Nys R, Givskov M, Kumar N, Kjelleberg S, Steinberg PD (2006) Furanones. Prog Mol Subcell Biol 42:55–86
DeAngelis KM, Lindow SE, Firestone MK (2008) Bacterial quorum sensing and nitrogen cycling in rhizosphere soil. FEMS Microbiol Ecol 66:197–207
Dobretsov S, Teplitski M, Paul V (2009) Mini-review: quorum sensing in the marine environment and its relationship to biofouling. Biofouling 25:413–427
Dong YH, Xu JL, Li XZ, Zhang LH (2000) AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. Proc Natl Acad Sci USA 97:3526–3531
Emerson RJt, Camesano TA (2004) Nanoscale investigation of pathogenic microbial adhesion to a biomaterial. Appl Environ Microbiol 70:6012–6022
Geisinger E, Muir TW, Novick RP (2009) agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proc Natl Acad Sci USA 106:1216–1221
Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, Parsek MR, Rice SA, Eberl L, Molin S, Hoiby N, Kjelleberg S, Givskov M (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148:87–102
Hooshangi S, Bentley WE (2008) From unicellular properties to multicellular behavior: bacteria quorum sensing circuitry and applications. Curr Opin Biotechnol 19:550–555
Janssens JC, Steenackers H, Robijns S, Gellens E, Levin J, Zhao H, Hermans K, De Coster D, Verhoeven TL, Marchal K, Vanderleyden J, De Vos DE, De Keersmaecker SC (2008) Brominated furanones inhibit biofilm formation by Salmonella enterica serovar Typhimurium. Appl Environ Microbiol 74:6639–6648
Joint I, Tait K, Wheeler G (2007) Cross-kingdom signalling: exploitation of bacterial quorum sensing molecules by the green seaweed Ulva. Philos Trans R Soc Lond B Biol Sci 362:1223–1233
Kavanaugh JS, Thoendel M, Horswill AR (2007) A role for type I signal peptidase in Staphylococcus aureus quorum sensing. Mol Microbiol 65:780–798
Keller L, Surette MG (2006) Communication in bacteria: an ecological and evolutionary perspective. Nat Rev Microbiol 4:249–258
Kobayashi H, Kaern M, Araki M, Chung K, Gardner TS, Cantor CR, Collins JJ (2004) Programmable cells: interfacing natural and engineered gene networks. Proc Natl Acad Sci USA 101:8414–8419
Kohler T, Buckling A, van Delden C (2009) Cooperation and virulence of clinical Pseudomonas aeruginosa populations. Proc Natl Acad Sci USA 106:6339–6344
Konings WN, Kok J, Kuipers OP, Poolman B (2000) Lactic acid bacteria: the bugs of the new millennium. Curr Opin Microbiol 3:276–282
Kruppa M (2009) Quorum sensing and Candida albicans. Mycoses 52:1–10
Kumari A, Pasini P, Daunert S (2008) Detection of bacterial quorum sensing N-acyl homoserine lactones in clinical samples. Anal Bioanal Chem 391:1619–1627
Li L, Hooi D, Chhabra SR, Pritchard D, Shaw PE (2004) Bacterial N-acylhomoserine lactone-induced apoptosis in breast carcinoma cells correlated with down-modulation of STAT3. Oncogene 23:4894–4902
Lin YH, Xu JL, Hu J, Wang LH, Ong SL, Leadbetter JR, Zhang LH (2003) Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes. Mol Microbiol 47:849–860
Liu D, Momb J, Thomas PW, Moulin A, Petsko GA, Fast W, Ringe D (2008) Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis. 1. Product-bound structures. Biochemistry 47:7706–7714
Liu X, Lagenaur LA, Simpson DA, Essenmacher KP, Frazier-Parker CL, Liu Y, Tsai D, Rao SS, Hamer DH, Parks TP, Lee PP, Xu Q (2006) Engineered vaginal Lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N. Antimicrob Agents Chemother 50:3250–3259
Lonn-Stensrud J, Petersen FC, Benneche T, Scheie AA (2007) Synthetic bromated furanone inhibits autoinducer-2-mediated communication and biofilm formation in oral streptococci. Oral Microbiol Immunol 22:340–346
Lutz R, Bujard H (1997) Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements. Nucleic Acids Res 25:1203–1210
Mae A, Montesano M, Koiv V, Palva ET (2001) Transgenic plants producing the bacterial pheromone N-acyl-homoserine lactone exhibit enhanced resistance to the bacterial phytopathogen Erwinia carotovora. Mol Plant Microbe Interact 14:1035–1042
McDougald D, Rice SA, Kjelleberg S (2007) Bacterial quorum sensing and interference by naturally occurring biomimics. Anal Bioanal Chem 387:445–453
Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199
Momb J, Wang C, Liu D, Thomas PW, Petsko GA, Guo H, Ringe D, Fast W (2008) Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis. 2. Substrate modeling and active site mutations. Biochemistry 47:7715–7725
Mullard A (2009) Microbiology: Tinker, bacteria, eukaryote, spy. Nature 459:159–161
Muller H, Westendorf C, Leitner E, Chernin L, Riedel K, Schmidt S, Eberl L, Berg G (2009) Quorum-sensing effects in the antagonistic rhizosphere bacterium Serratia plymuthica HRO-C48. FEMS Microbiol Ecol 67:468–478
Neddermann P, Gargioli C, Muraglia E, Sambucini S, Bonelli F, De Francesco R, Cortese R (2003) A novel, inducible, eukaryotic gene expression system based on the quorum-sensing transcription factor TraR. EMBO Rep 4:159–165
Ng WL, Bassler BL (2009) Bacterial quorum-sensing network architectures. Annu Rev Genet 43:197–222
Novick RP, Geisinger E (2008) Quorum sensing in staphylococci. Annu Rev Genet 42:541–564
Oliver CM, Schaefer AL, Greenberg EP, Sufrin JR (2009) Microwave synthesis and evaluation of phenacylhomoserine lactones as anticancer compounds that minimally activate quorum sensing pathways in Pseudomonas aeruginosa. J Med Chem 52:1569–1575
Olsen SM, Pedersen LT, Laursen MH, Kiil S, Dam-Johansen K (2007) Enzyme-based antifouling coatings: a review. Biofouling 23:369–383
Pacheco AR, Sperandio V (2009) Inter-kingdom signaling: chemical language between bacteria and host. Curr Opin Microbiol 12:192–198
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 71:2632–2641
Purnick PE, Weiss R (2009) The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol 10:410–422
Rao S, Hu S, McHugh L, Lueders K, Henry K, Zhao Q, Fekete RA, Kar S, Adhya S, Hamer DH (2005) Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci USA 102:11993–11998
Rasmussen TB, Givskov M (2006) Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296:149–161
Rasmussen TB, Skindersoe ME, Bjarnsholt T, Phipps RK, Christensen KB, Jensen PO, Andersen JB, Koch B, Larsen TO, Hentzer M, Eberl L, Hoiby N, Givskov M (2005) Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151:1325–1340
Ren D, Bedzyk LA, Ye RW, Thomas SM, Wood TK (2004) Differential gene expression shows natural brominated furanones interfere with the autoinducer-2 bacterial signaling system of Escherichia coli. Biotechnol Bioeng 88:630–642
Ren D, Sims JJ, 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 3:731–736
Rickard AH, Palmer RJ Jr, Blehert DS, Campagna SR, Semmelhack MF, Egland PG, Bassler BL, Kolenbrander PE (2006) Autoinducer 2: a concentration-dependent signal for mutualistic bacterial biofilm growth. Mol Microbiol 60:1446–1456
Sanchez-Contreras M, Bauer WD, Gao M, Robinson JB, Allan Downie J (2007) Quorum-sensing regulation in rhizobia and its role in symbiotic interactions with legumes. Philos Trans R Soc Lond B Biol Sci 362:1149–1163
Schmidt S, Blom JF, Pernthaler J, Berg G, Baldwin A, Mahenthiralingam E, Eberl L (2009) Production of the antifungal compound pyrrolnitrin is quorum sensing-regulated in members of the Burkholderia cepacia complex. Environ Microbiol 11:1422–1437
Silagyi K, Kim SH, Lo YM, Wei CI (2009) Production of biofilm and quorum sensing by Escherichia coli O157:H7 and its transfer from contact surfaces to meat, poultry, ready-to-eat deli, and produce products. Food Microbiol 26:514–519
Steindler L, Venturi V (2007) Detection of quorum-sensing N-acyl homoserine lactone signal molecules by bacterial biosensors. FEMS Microbiol Lett 266:1–9
Stock AM, Robinson VL, Goudreau PN (2000) Two-component signal transduction. Annu Rev Biochem 69:183–215
Stoltz DA, Ozer EA, Taft PJ, Barry M, Liu L, Kiss PJ, Moninger TO, Parsek MR, Zabner J (2008) Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1. J Clin Invest 118:3123–3131
Teiber JF, Horke S, Haines DC, Chowdhary PK, Xiao J, Kramer GL, Haley RW, Draganov DI (2008) Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone. Infect Immun 76:2512–2519
Thiel V, Kunze B, Verma P, Wagner-Dobler I, Schulz S (2009) New structural variants of homoserine lactones in bacteria. Chembiochem 10:1861–1868
Thoendel M, Horswill AR (2009) Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem 284:21828–21838
Turovskiy Y, Kashtanov D, Paskhover B, Chikindas ML (2007) Quorum sensing: fact, fiction, and everything in between. Adv Appl Microbiol 62:191–234
Uroz S, Chhabra SR, Camara M, Williams P, Oger P, Dessaux Y (2005) N-Acylhomoserine lactone quorum-sensing molecules are modified and degraded by Rhodococcus erythropolis W2 by both amidolytic and novel oxidoreductase activities. Microbiology 151:3313–3322
Uroz S, Dessaux Y, Oger P (2009) Quorum sensing and quorum quenching: the yin and yang of bacterial communication. Chembiochem 10:205–216
Uroz S, Heinonsalo J (2008) Degradation of N-acyl homoserine lactone quorum sensing signal molecules by forest root-associated fungi. FEMS Microbiol Ecol 65:271–278
Vendeville A, Winzer K, Heurlier K, Tang CM, Hardie KR (2005) Making ‘sense’ of metabolism: autoinducer-2, LuxS and pathogenic bacteria. Nat Rev Microbiol 3:383–396
Wagner VE, Gillis RJ, Iglewski BH (2004) Transcriptome analysis of quorum-sensing regulation and virulence factor expression in Pseudomonas aeruginosa. Vaccine 22(Suppl 1):S15–S20
Weber W, Daoud-El Baba M, Fussenegger M (2007) Synthetic ecosystems based on airborne inter- and intrakingdom communication. Proc Natl Acad Sci USA 104:10435–10440
Weber W, Fussenegger M (2009) Engineering of synthetic mammalian gene networks. Chem Biol 16:287–297
Weber W, Malphettes L, de Jesus M, Schoenmakers R, El-Baba MD, Spielmann M, Keller B, Weber CC, van de Wetering P, Aubel D, Wurm FM, Fussenegger M (2005) Engineered Streptomyces quorum-sensing components enable inducible siRNA-mediated translation control in mammalian cells and adjustable transcription control in mice. J Gene Med 7:518–525
Weber W, Schoenmakers R, Spielmann M, El-Baba MD, Folcher M, Keller B, Weber CC, Link N, van de Wetering P, Heinzen C, Jolivet B, Sequin U, Aubel D, Thompson CJ, Fussenegger M (2003) Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice. Nucleic Acids Res 31:e71
Williams P, Camara M (2009) Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 12:182–191
Williams SC, Patterson EK, Carty NL, Griswold JA, Hamood AN, Rumbaugh KP (2004) Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells. J Bacteriol 186:2281–2287
Wolanin PM, Thomason PA, Stock JB (2002) Histidine protein kinases: key signal transducers outside the animal kingdom. Genome Biol 3:reviews 3013.1–3013.8
Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S (2000) Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther 7:269–274
Yeon KM, Cheong WS, Oh HS, Lee WN, Hwang BK, Lee CH, Beyenal H, Lewandowski Z (2009) Quorum sensing: a new biofouling control paradigm in a membrane bioreactor for advanced wastewater treatment. Environ Sci Technol 43:380–385
Yoshida A, Ansai T, Takehara T, Kuramitsu HK (2005) LuxS-based signaling affects Streptococcus mutans biofilm formation. Appl Environ Microbiol 71:2372–2380
You L, Cox RS 3rd, Weiss R, Arnold FH (2004) Programmed population control by cell–cell communication and regulated killing. Nature 428:868–871
Yu YA, Shabahang S, Timiryasova TM, Zhang Q, Beltz R, Gentschev I, Goebel W, Szalay AA (2004) Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins. Nat Biotechnol 22:313–320
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Choudhary, S., Schmidt-Dannert, C. Applications of quorum sensing in biotechnology. Appl Microbiol Biotechnol 86, 1267–1279 (2010). https://doi.org/10.1007/s00253-010-2521-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-010-2521-7