Quorum sensing for population-level control of bacteria and potential therapeutic applications

Quorum sensing (QS), a microbial cell-to-cell communication process, dynamically regulates a variety of metabolism and physiological activities. In this review, we provide an update on QS applications based on autoinducer molecules including acyl-homoserine lactones (AHLs), auto-inducing peptides (AIPs), autoinducer 2 (AI-2) and indole in population-level control of bacteria, and highlight the potential in developing novel clinical therapies. We summarize the development in the combination of various genetic circuits such as genetic oscillators, toggle switches and logic gates with AHL-based QS devices in Gram-negative bacteria. An overview is then offered to the state-of-the-art of much less researched applications of AIP-based QS devices with Gram-positive bacteria, followed by a review of the applications of AI-2 and indole based QS for interspecies communication among microbial communities. Building on these general-purpose QS applications, we highlight the disruptions and manipulations of QS devices as potential clinical therapies for diseases caused by biofilm formation, antibiotic resistance and the phage invasion. The last part of reviewed literature is dedicated to mathematical modelling for QS applications. Finally, the key challenges and future perspectives of QS applications in monoclonal synthetic biology and synthetic ecology are discussed.

[1]  Ron Weiss,et al.  Genetically programmable pathogen sense and destroy. , 2013, ACS synthetic biology.

[2]  Christopher A. Voigt,et al.  Genetic programs constructed from layered logic gates in single cells , 2012, Nature.

[3]  J. Costerton,et al.  Bacterial biofilms in nature and disease. , 1987, Annual review of microbiology.

[4]  Claudia Schmidt-Dannert,et al.  Applications of quorum sensing in biotechnology , 2010, Applied Microbiology and Biotechnology.

[5]  Gürol M. Süel,et al.  Ion channels enable electrical communication in bacterial communities , 2015, Nature.

[6]  J. Hasty,et al.  Synthetic gene network for entraining and amplifying cellular oscillations. , 2002, Physical review letters.

[7]  R. Grenha,et al.  Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR , 2012, Proceedings of the National Academy of Sciences.

[8]  Qian Ma,et al.  Synthetic cell–cell communication in a three-species consortium for one-step vitamin C fermentation , 2019, Biotechnology Letters.

[9]  K. Tanaka,et al.  Structure of the 5′ upstream region and the regulation of the rpoS gene of Escherichia coli , 1994, Molecular and General Genetics MGG.

[10]  J. Qiao,et al.  Improving nitrogen source utilization from defatted soybean meal for nisin production by enhancing proteolytic function of Lactococcus lactis F44 , 2017, Scientific Reports.

[11]  Bonnie L. Bassler,et al.  Interference with AI-2-mediated bacterial cell–cell communication , 2005, Nature.

[12]  Leopold N. Green,et al.  Control of bacterial population density with population feedback and molecular sequestration , 2017, bioRxiv.

[13]  J. Qiao,et al.  A novel small RNA S042 increases acid tolerance in Lactococcus lactis F44. , 2018, Biochemical and biophysical research communications.

[14]  L. Tsimring,et al.  A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis , 2017, Nature Microbiology.

[15]  Christopher A. Voigt,et al.  Principles of genetic circuit design , 2014, Nature Methods.

[16]  L. Tsimring,et al.  Entrainment of a Population of Synthetic Genetic Oscillators , 2011, Science.

[17]  Rashidul Haque,et al.  Members of the human gut microbiota involved in recovery from Vibrio cholerae infection , 2014, Nature.

[18]  Stephen P. Diggle,et al.  Progress in and promise of bacterial quorum sensing research , 2017, Nature.

[19]  T. Xue,et al.  Autoinducer-2 increases biofilm formation via an ica- and bhp-dependent manner in Staphylococcus epidermidis RP62A. , 2015, Microbes and infection.

[20]  B. Bassler,et al.  Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms. , 2019, Cell host & microbe.

[21]  M. Kube,et al.  ‘Candidatus Phytoplasma phoenicium’ associated with almond witches’-broom disease: from draft genome to genetic diversity among strain populations , 2015, BMC Microbiology.

[22]  Knut Drescher,et al.  A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation , 2013, Proceedings of the National Academy of Sciences.

[23]  E. Greenberg,et al.  A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases , 2013, Proceedings of the National Academy of Sciences.

[24]  Antoine M. van Oijen,et al.  Ever-fluctuating single enzyme molecules: Michaelis-Menten equation revisited , 2006, Nature chemical biology.

[25]  K. Baek,et al.  The multifaceted roles of the interspecies signalling molecule indole in Agrobacterium tumefaciens. , 2015, Environmental microbiology.

[26]  D. Lereclus,et al.  Quorum Sensing in Bacillus thuringiensis Is Required for Completion of a Full Infectious Cycle in the Insect , 2014, Toxins.

[27]  Sean M. Kearney,et al.  Salt-responsive gut commensal modulates TH17 axis and disease , 2017, Nature.

[28]  Arul Jayaraman,et al.  Indole is an inter-species biofilm signal mediated by SdiA , 2007, BMC Microbiology.

[29]  Qing Li,et al.  Inter-kingdom signaling between gut microbiota and their host , 2019, Cellular and Molecular Life Sciences.

[30]  G. Núñez,et al.  Regulated Virulence Controls the Ability of a Pathogen to Compete with the Gut Microbiota , 2012, Science.

[31]  Howard J. Li,et al.  Rapid and tunable post-translational coupling of genetic circuits , 2014, Nature.

[32]  B. Bassler,et al.  Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 in Escherichia coli , 2005, Journal of bacteriology.

[33]  Arpan A Bandyopadhyay,et al.  Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis , 2017, MicrobiologyOpen.

[34]  L. Fontaine,et al.  Modeling of the ComRS Signaling Pathway Reveals the Limiting Factors Controlling Competence in Streptococcus thermophilus , 2015, Front. Microbiol..

[35]  Hideki Kobayashi,et al.  Analysis and design of a genetic circuit for dynamic metabolic engineering. , 2013, ACS synthetic biology.

[36]  Wai-Leung Ng,et al.  Specificity and complexity in bacterial quorum-sensing systems , 2016, FEMS microbiology reviews.

[37]  M. Federle,et al.  Peptide pheromone signaling in Streptococcus and Enterococcus. , 2014, FEMS microbiology reviews.

[38]  Jintae Lee,et al.  Indole oxidation enhances electricity production in an E. coli-catalyzed microbial fuel cell , 2014, Biotechnology and Bioprocess Engineering.

[39]  Laurence Zitvogel,et al.  Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors , 2018, Science.

[40]  Ana Rodríguez,et al.  Phage or foe: an insight into the impact of viral predation on microbial communities , 2018, The ISME Journal.

[41]  Jeff Hasty,et al.  Quorum Sensing Communication Modules for Microbial Consortia. , 2016, ACS synthetic biology.

[42]  J. Prescott,et al.  The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry , 2017, Infection and Immunity.

[43]  C. Ubeda,et al.  Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota. , 2015, Cell reports.

[44]  T. Wood,et al.  Quorum sensing enhancement of the stress response promotes resistance to quorum quenching and prevents social cheating , 2014, The ISME Journal.

[45]  Chenhong Zhang,et al.  Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes , 2018, Science.

[46]  K. Xavier,et al.  AI-2-mediated signalling in bacteria. , 2013, FEMS microbiology reviews.

[47]  S. Leibler,et al.  Biological rhythms: Circadian clocks limited by noise , 2000, Nature.

[48]  M. Federle,et al.  Rgg protein structure–function and inhibition by cyclic peptide compounds , 2015, Proceedings of the National Academy of Sciences.

[49]  Keshav K. Nepal,et al.  Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products. , 2019, Biotechnology advances.

[50]  Shutao Ma,et al.  Recent Advances in the Discovery of PqsD Inhibitors as Antimicrobial Agents , 2017, ChemMedChem.

[51]  Frank Jülicher,et al.  Chemical event chain model of coupled genetic oscillators. , 2018, Physical review. E.

[52]  Jeffrey D Orth,et al.  What is flux balance analysis? , 2010, Nature Biotechnology.

[53]  J. Hasty,et al.  Synchronizing genetic relaxation oscillators by intercell signaling , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[54]  T. Baker,et al.  A specificity-enhancing factor for the ClpXP degradation machine. , 2000, Science.

[55]  S. Rice,et al.  Biofilms: an emergent form of bacterial life , 2016, Nature Reviews Microbiology.

[56]  Mary A. Arugula,et al.  Molecular AND logic gate based on bacterial anaerobic respiration. , 2012, Chemical communications.

[57]  Scott N. Dean,et al.  Burkholderia Diffusible Signal Factor Signals to Francisella novicida To Disperse Biofilm and Increase Siderophore Production , 2015, Applied and Environmental Microbiology.

[58]  U. Sauer,et al.  Coordination of microbial metabolism , 2014, Nature Reviews Microbiology.

[59]  Tian Ding,et al.  Quorum-Sensing Regulation of Antimicrobial Resistance in Bacteria , 2020, Microorganisms.

[60]  M. Bennett,et al.  A fast, robust, and tunable synthetic gene oscillator , 2008, Nature.

[61]  T. Takumi,et al.  Potential contribution of tandem circadian enhancers to nonlinear oscillations in clock gene expression , 2017, Molecular biology of the cell.

[62]  T. Hanai,et al.  Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production. , 2019, Metabolic engineering.

[63]  M. Gölgeli,et al.  Mathematical Modelling of Bacterial Quorum Sensing: A Review , 2016, Bulletin of mathematical biology.

[64]  Lian-Hui Zhang,et al.  Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase , 2001, Nature.

[65]  M. Surette,et al.  Communication in bacteria: an ecological and evolutionary perspective , 2006, Nature Reviews Microbiology.

[66]  Adam M. Feist,et al.  The biomass objective function. , 2010, Current opinion in microbiology.

[67]  Manjunath Hegde,et al.  Synthetic quorum-sensing circuit to control consortial biofilm formation and dispersal in a microfluidic device , 2012, Nature Communications.

[68]  J. Qiao,et al.  Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides. , 2018, Metabolic engineering.

[69]  A. Hill.  The Combinations of Haemoglobin with Oxygen and with Carbon Monoxide. I. , 1913, The Biochemical journal.

[70]  B. McClane,et al.  Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System , 2015, Journal of Bacteriology.

[71]  C. Collins,et al.  Synthetic Quorum Sensing and Cell-Cell Communication in Gram-Positive Bacillus megaterium. , 2016, ACS synthetic biology.

[72]  P. Silver,et al.  Dynamics in the mixed microbial concourse. , 2010, Genes & development.

[73]  M. Zhang,et al.  Attenuation of Edwardsiella tarda Virulence by Small Peptides That Interfere with LuxS/Autoinducer Type 2 Quorum Sensing , 2009, Applied and Environmental Microbiology.

[74]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[75]  G. Stephanopoulos,et al.  Metabolic engineering: past and future. , 2013, Annual review of chemical and biomolecular engineering.

[76]  Jay D. Keasling,et al.  Engineering Static and Dynamic Control of Synthetic Pathways , 2010, Cell.

[77]  J. Xavier.  Social interaction in synthetic and natural microbial communities , 2011, Molecular systems biology.

[78]  Gabriel C. Wu,et al.  Synthetic protein scaffolds provide modular control over metabolic flux , 2009, Nature Biotechnology.

[79]  Chris P. Barnes,et al.  A Statistical Approach Reveals Designs for the Most Robust Stochastic Gene Oscillators , 2015, bioRxiv.

[80]  M. Win,et al.  A modular and extensible RNA-based gene-regulatory platform for engineering cellular function , 2007, Proceedings of the National Academy of Sciences.

[81]  Lingchong You,et al.  Spatiotemporal modulation of biodiversity in a synthetic chemical-mediated ecosystem , 2009, Nature chemical biology.

[82]  Orkun S. Soyer,et al.  Engineering microbial communities using thermodynamic principles and electrical interfaces. , 2018, Current opinion in biotechnology.

[83]  J. S. Chuang,et al.  Engineering multicellular traits in synthetic microbial populations. , 2012, Current opinion in chemical biology.

[84]  Alan R. Davidson,et al.  Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system , 2012, Nature.

[85]  Chueh Loo Poh,et al.  Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen , 2011, Molecular systems biology.

[86]  S. K. Schmidt,et al.  Models for the kinetics of biodegradation of organic compounds not supporting growth , 1985, Applied and environmental microbiology.

[87]  W. Newton,et al.  Formation and Interrelationships of Tryptophanase and Tryptophan Synthetases in Escherichia coli , 1965, Journal of bacteriology.

[88]  T. Wood,et al.  Indole Production Promotes Escherichia coli Mixed-Culture Growth with Pseudomonas aeruginosa by Inhibiting Quorum Signaling , 2011, Applied and Environmental Microbiology.

[89]  U. Keyser,et al.  Indole prevents Escherichia coli cell division by modulating membrane potential , 2012, Biochimica et biophysica acta.

[90]  Fabian J Theis,et al.  Publisher Correction: Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway , 2018, Nature Communications.

[91]  Hyun Seob Cho,et al.  Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus , 2013, Applied Microbiology and Biotechnology.

[92]  S. Abedon.  Spatial Vulnerability: Bacterial Arrangements, Microcolonies, and Biofilms as Responses to Low Rather than High Phage Densities , 2012, Viruses.

[93]  Xingyuan Li,et al.  Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and virulence production in a dose-dependent manner , 2015, BMC Microbiology.

[94]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[95]  K. Severinov,et al.  Come Together: CRISPR-Cas Immunity Senses the Quorum. , 2016, Molecular cell.

[96]  D. Summers,et al.  Indole signalling contributes to the stable maintenance of Escherichia coli multicopy plasmids , 2007, Molecular microbiology.

[97]  A. Griffin,et al.  Cooperation and conflict in quorum-sensing bacterial populations , 2007, Nature.

[98]  M. Crotty,et al.  Terminal room disinfection: how much BETR can it get? , 2017, The Lancet.

[99]  William E Bentley,et al.  Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models , 2017, Nature Communications.

[100]  Bonnie L. Bassler,et al.  Quorum sensing signal–response systems in Gram-negative bacteria , 2016, Nature Reviews Microbiology.

[101]  E. Katz,et al.  Programming the quorum sensing-based AND gate in Shewanella oneidensis for logic gated-microbial fuel cells. , 2015, Chemical communications.

[102]  C. Bell,et al.  Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase. , 2006, Journal of medicinal chemistry.

[103]  Chueh Loo Poh,et al.  Reprogramming microbes to be pathogen-seeking killers. , 2014, ACS synthetic biology.

[104]  Cesar A. Arias,et al.  The rise of the Enterococcus: beyond vancomycin resistance , 2012, Nature Reviews Microbiology.

[105]  Stephen P. Diggle,et al.  Targeting virulence: can we make evolution-proof drugs? , 2014, Nature Reviews Microbiology.

[106]  S. van Calenbergh,et al.  Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR , 2008, BMC Microbiology.

[107]  Jintae Lee,et al.  Indole-3-acetaldehyde from Rhodococcus sp. BFI 332 inhibits Escherichia coli O157:H7 biofilm formation , 2012, Applied Microbiology and Biotechnology.

[108]  Joerg M. Buescher,et al.  Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism , 2012, Science.

[109]  Ivan Razinkov,et al.  Sensing array of radically coupled genetic biopixels , 2011, Nature.

[110]  S. D. De Keersmaecker,et al.  Let LuxS speak up in AI-2 signaling. , 2006, Trends in microbiology.

[111]  E. Greenberg,et al.  Bacterial Quorum Sensing and Metabolic Incentives to Cooperate , 2012, Science.

[112]  Vipin Chandra Kalia,et al.  Quorum sensing inhibitors: an overview. , 2013, Biotechnology advances.

[113]  R. Weiss,et al.  Programmed population control by cell–cell communication and regulated killing , 2004, Nature.

[114]  Tom Coenye,et al.  Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics In Vitro and In Vivo , 2011, Antimicrobial Agents and Chemotherapy.

[115]  L. Hmelo.  Quorum Sensing in Marine Microbial Environments. , 2017, Annual review of marine science.

[116]  Asad U. Khan,et al.  Inhibitory effect of zingiber officinale towards Streptococcus mutans virulence and caries development: in vitro and in vivo studies , 2015, BMC Microbiology.

[117]  M. Kleerebezem,et al.  Stress Physiology of Lactic Acid Bacteria , 2016, Microbiology and Molecular Reviews.

[118]  G. Bongaerts,et al.  A reassessment of the PROPATRIA study and its implications for probiotic therapy , 2016, Nature Biotechnology.

[119]  Adam L. Meadows,et al.  Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation. , 2010, Metabolic engineering.

[120]  K. Foster,et al.  The evolution of the host microbiome as an ecosystem on a leash , 2017, Nature.

[121]  Yiannis N. Kaznessis,et al.  Modified Lactic Acid Bacteria Detect and Inhibit Multiresistant Enterococci , 2014, ACS synthetic biology.

[122]  Douglas R. Call,et al.  Transcriptome analysis of Vibrio parahaemolyticus in type III secretion system 1 inducing conditions , 2014, Front. Cell. Infect. Microbiol..

[123]  B. Bassler,et al.  A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation , 2017, Nature chemical biology.

[124]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[125]  Takafumi Miyamoto,et al.  Synthesizing biomolecule-based Boolean logic gates. , 2013, ACS synthetic biology.

[126]  G. Fichant,et al.  Direct involvement of DprA, the transformation-dedicated RecA loader, in the shut-off of pneumococcal competence , 2012, Proceedings of the National Academy of Sciences.

[127]  Jeff Hasty,et al.  Synchronized DNA cycling across a bacterial population , 2017, Nature Genetics.

[128]  M. Omar Din,et al.  Synchronized cycles of bacterial lysis for in vivo delivery , 2016, Nature.

[129]  K. F. Chen,et al.  Observation of B+-ppK+ , 2002 .

[130]  Vishal Singh,et al.  Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. , 2018, Cell host & microbe.

[131]  T. Hanai,et al.  Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch. , 2014, Metabolic engineering.

[132]  Qunyuan Zhang,et al.  Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children , 2014, Nature.

[133]  I. Hwang,et al.  Bacterial quorum sensing and metabolic slowing in a cooperative population , 2014, Proceedings of the National Academy of Sciences.

[134]  James J Collins,et al.  Designing microbial consortia with defined social interactions , 2018, Nature Chemical Biology.

[135]  Christina A. Cuomo,et al.  Intracellular Action of a Secreted Peptide Required for Fungal Virulence. , 2016, Cell host & microbe.

[136]  M. Federle,et al.  A novel double‐tryptophan peptide pheromone controls competence in Streptococcus spp. via an Rgg regulator , 2010, Molecular microbiology.

[137]  Y. Chen,et al.  Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa , 2016, Journal of applied microbiology.

[138]  K. Winzer,et al.  An agr Quorum Sensing System That Regulates Granulose Formation and Sporulation in Clostridium acetobutylicum , 2011, Applied and Environmental Microbiology.

[139]  T. Elston,et al.  Stochasticity in gene expression: from theories to phenotypes , 2005, Nature Reviews Genetics.

[140]  O. Dror,et al.  Virulence and in planta movement of Xanthomonas hortorum pv. pelargonii are affected by the diffusible signal factor (DSF)-dependent quorum sensing system. , 2015, Molecular plant pathology.

[141]  Y. Benenson.  Biomolecular computing systems: principles, progress and potential , 2012, Nature Reviews Genetics.

[142]  Quanfeng Liang,et al.  Autoinduced AND Gate Controls Metabolic Pathway Dynamically in Response to Microbial Communities and Cell Physiological State. , 2017, ACS synthetic biology.

[143]  Peng Xu,et al.  Production of chemicals using dynamic control of metabolic fluxes. , 2018, Current opinion in biotechnology.

[144]  Tian Yang,et al.  Structure-Function Analyses of a Staphylococcus epidermidis Autoinducing Peptide Reveals Motifs Critical for AgrC-type Receptor Modulation. , 2016, ACS chemical biology.

[145]  Véronique Monnet,et al.  Peptide conversations in Gram-positive bacteria , 2014, Critical reviews in microbiology.

[146]  B. Bassler,et al.  Structural identification of a bacterial quorum-sensing signal containing boron , 2002, Nature.

[147]  Nikhil U. Nair,et al.  Synthetic biology in probiotic lactic acid bacteria: At the frontier of living therapeutics. , 2018, Current opinion in biotechnology.

[148]  S. D. De Keersmaecker,et al.  Impact of luxS and Suppressor Mutations on the Gastrointestinal Transit of Lactobacillus rhamnosus GG , 2008, Applied and Environmental Microbiology.

[149]  E. Greenberg,et al.  Bacterial quorum sensing, cooperativity, and anticipation of stationary-phase stress , 2012, Proceedings of the National Academy of Sciences.

[150]  Jintae Lee,et al.  Indole‐associated predator–prey interactions between the nematode Caenorhabditis elegans and bacteria , 2017, Environmental microbiology.

[151]  J. M. Dow,et al.  Diffusible signal factor‐dependent quorum sensing in pathogenic bacteria and its exploitation for disease control , 2017, Journal of applied microbiology.

[152]  Fuzhong Zhang,et al.  Applications and advances of metabolite biosensors for metabolic engineering. , 2015, Metabolic engineering.

[153]  Jintae Lee,et al.  Indole and 3-indolylacetonitrile inhibit spore maturation in Paenibacillus alvei , 2011, BMC Microbiology.

[154]  Jasmine Shong,et al.  Towards synthetic microbial consortia for bioprocessing. , 2012, Current opinion in biotechnology.

[155]  A. Grenha,et al.  Multifunctional Nanocarriers for Lung Drug Delivery , 2020, Nanomaterials.

[156]  Lian-Hui Zhang,et al.  Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens , 2014, BMC Microbiology.

[157]  J. Collins,et al.  Programmable cells: interfacing natural and engineered gene networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[158]  Taizo Hanai,et al.  Self-induced metabolic state switching by a tunable cell density sensor for microbial isopropanol production. , 2015, Metabolic engineering.

[159]  Andrew B Goryachev,et al.  Understanding bacterial cell-cell communication with computational modeling. , 2011, Chemical reviews.

[160]  M. di Bernardo,et al.  A comparative analysis of synthetic genetic oscillators , 2010, Journal of The Royal Society Interface.

[161]  David R. Johnson,et al.  Synthetic microbial ecology and the dynamic interplay between microbial genotypes. , 2016, FEMS microbiology reviews.

[162]  Martin Fussenegger,et al.  Designer cells programming quorum-sensing interference with microbes , 2018, Nature Communications.

[163]  David Lebeaux,et al.  Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics , 2014, Microbiology and Molecular Reviews.

[164]  F. Weissing,et al.  Quorum sensing integrates environmental cues, cell density and cell history to control bacterial competence , 2016, Nature Communications.

[165]  Nikolaos Anesiadis,et al.  Engineering metabolism through dynamic control. , 2015, Current opinion in biotechnology.

[166]  Nigel P. Minton,et al.  Regulation of Neurotoxin Production and Sporulation by a Putative agrBD Signaling System in Proteolytic Clostridium botulinum , 2010, Applied and Environmental Microbiology.

[167]  Christopher A. Voigt,et al.  Genetic circuit design automation , 2016, Science.

[168]  Lian-Hui Zhang,et al.  The DSF Family of Quorum Sensing Signals: Diversity, Biosynthesis, and Turnover. , 2017, Trends in microbiology.

[169]  E. Greenberg,et al.  Sociomicrobiology: the connections between quorum sensing and biofilms. , 2005, Trends in microbiology.

[170]  K. Coyte,et al.  Understanding Competition and Cooperation within the Mammalian Gut Microbiome , 2019, Current Biology.

[171]  B. Tu,et al.  Metabolic cycles as an underlying basis of biological oscillations , 2006, Nature Reviews Molecular Cell Biology.

[172]  R. Gardan,et al.  Quorum‐sensing regulators in Gram‐positive bacteria: ‘cherchez le peptide ’ , 2015, Molecular microbiology.

[173]  Nan Shang,et al.  D-Ribose Interferes with Quorum Sensing to Inhibit Biofilm Formation of Lactobacillus paraplantarum L-ZS9 , 2017, Front. Microbiol..

[174]  C. Riedel,et al.  AI-2 to the rescue against antibiotic-induced intestinal dysbiosis? , 2015, Trends in microbiology.

[175]  W. R. Cluett,et al.  Dynamic metabolic engineering for increasing bioprocess productivity. , 2008, Metabolic engineering.

[176]  M. Schuster,et al.  Core Principles of Bacterial Autoinducer Systems , 2015, Microbiology and Molecular Reviews.

[177]  M. Federle,et al.  Structural Insights into Streptococcal Competence Regulation by the Cell-to-Cell Communication System ComRS , 2016, PLoS pathogens.

[178]  G. Gościniak,et al.  A proposed role for diffusible signal factors in the biofilm formation and morphological transformation of Helicobacter pylori. , 2017, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[179]  Sayan Mukherjee,et al.  A unifying framework for interpreting and predicting mutualistic systems , 2019, Nature Communications.

[180]  M. Aumont-Nicaise,et al.  A cell–cell communication system regulates protease production during sporulation in bacteria of the Bacillus cereus group , 2011, Molecular microbiology.

[181]  P. Rather,et al.  Indole Can Act as an Extracellular Signal inEscherichia coli , 2001, Journal of bacteriology.

[182]  Rahul Sarpeshkar,et al.  Synthetic analog computation in living cells , 2013, Nature.

[183]  W. van Schaik,et al.  Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era. , 2013, Current opinion in microbiology.

[184]  Heleen Van Acker,et al.  Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. , 2014, Trends in microbiology.

[185]  S. Zouhir,et al.  Peptide-binding dependent conformational changes regulate the transcriptional activity of the quorum-sensor NprR , 2013, Nucleic acids research.

[186]  Lingchong You,et al.  Emerging strategies for engineering microbial communities. , 2019, Biotechnology advances.

[187]  J. Collins,et al.  Bacterial charity work leads to population-wide resistance , 2010, Nature.

[188]  James J. Collins,et al.  Signaling-Mediated Bacterial Persister Formation , 2011, Nature chemical biology.

[189]  Hasan Baig,et al.  Simulation Approach for Timing Analysis of Genetic Logic Circuits. , 2017, ACS synthetic biology.

[190]  Peter C. Fineran,et al.  Regulation of CRISPR-Cas adaptive immune systems. , 2017, Current opinion in microbiology.

[191]  Richard A. Juneau,et al.  Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling , 2010, mBio.

[192]  A. Marina,et al.  Structural Basis of Rap Phosphatase Inhibition by Phr Peptides , 2013, PLoS biology.

[193]  A. Tzika,et al.  Identification of Anti-virulence Compounds That Disrupt Quorum-Sensing Regulated Acute and Persistent Pathogenicity , 2014, PLoS pathogens.

[194]  D. Garmyn,et al.  The Agr communication system provides a benefit to the populations of Listeria monocytogenes in soil , 2014, Front. Cell. Infect. Microbiol..

[195]  R. Weiss,et al.  Directed evolution of a genetic circuit , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[196]  D. Kressler,et al.  Hold on to your friends: Dedicated chaperones of ribosomal proteins , 2017, BioEssays : news and reviews in molecular, cellular and developmental biology.

[197]  J. M. Dow,et al.  Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa , 2008, Molecular microbiology.

[198]  Kristala L. J. Prather,et al.  Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit , 2017, Nature Biotechnology.

[199]  T. Wood,et al.  Roles of indole as an interspecies and interkingdom signaling molecule. , 2015, Trends in microbiology.

[200]  M. Schuster,et al.  Social interactions in bacterial cell-cell signaling. , 2017, FEMS microbiology reviews.

[201]  James J Collins,et al.  Antibiotics and the gut microbiota. , 2014, The Journal of clinical investigation.

[202]  G. Vinnicombe,et al.  Synchronous long-term oscillations in a synthetic gene circuit , 2016, Nature.

[203]  A. Griffin,et al.  Indole: An evolutionarily conserved influencer of behavior across kingdoms , 2017, BioEssays : news and reviews in molecular, cellular and developmental biology.

[204]  Jürgen Tomasch,et al.  The Alternative Sigma Factor SigX Controls Bacteriocin Synthesis and Competence, the Two Quorum Sensing Regulated Traits in Streptococcus mutans , 2015, PLoS genetics.

[205]  S. Hagen,et al.  Intracellular signaling through the comRS system in Streptococcus mutans genetic competence , 2018, bioRxiv.

[206]  Evgeny Katz,et al.  Bacteria-based AND logic gate: a decision-making and self-powered biosensor. , 2011, Chemical communications.

[207]  Bonnie L Bassler,et al.  Bacterial quorum sensing in complex and dynamically changing environments , 2019, Nature Reviews Microbiology.

[208]  Hao Song,et al.  Synthetic microbial consortia: from systematic analysis to construction and applications. , 2014, Chemical Society reviews.

[209]  B. Bassler,et al.  Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence , 1993, Molecular microbiology.

[210]  Christopher A. Voigt,et al.  Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ , 2011, Nature.

[211]  Rotem Sorek,et al.  Communication between viruses guides lysis-lysogeny decisions , 2016, Nature.

[212]  J. Lolkema,et al.  Convergent evolution of the arginine deiminase pathway: the ArcD and ArcE arginine/ornithine exchangers , 2016, MicrobiologyOpen.

[213]  Kristala L. J. Prather,et al.  Layered dynamic regulation for improving metabolic pathway productivity in Escherichia coli , 2018, Proceedings of the National Academy of Sciences.

[214]  F. Wisniewski-Dyé,et al.  Cell-cell signalling in bacteria: not simply a matter of quorum. , 2009, FEMS microbiology ecology.

[215]  S. Hagen,et al.  Intracellular Signaling by the comRS System in Streptococcus mutans Genetic Competence , 2018, mSphere.

[216]  Jagjit S Ludu,et al.  The Francisella pathogenicity island protein IglA localizes to the bacterial cytoplasm and is needed for intracellular growth , 2007, BMC Microbiology.

[217]  E. Guédon,et al.  Quorum-Sensing Regulation of the Production of Blp Bacteriocins in Streptococcus thermophilus , 2007, Journal of bacteriology.

[218]  G. Evans,et al.  Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems , 2016, Molecular cell.

[219]  Jing Yuan,et al.  Bifidobacteria Exhibit LuxS-Dependent Autoinducer 2 Activity and Biofilm Formation , 2014, PloS one.

[220]  Minyong Li,et al.  Inhibitors and antagonists of bacterial quorum sensing , 2009, Medicinal research reviews.

[221]  T. Wood,et al.  Rhizoremediation of Trichloroethylene by a Recombinant, Root-Colonizing Pseudomonas fluorescensStrain Expressing Toluene ortho-Monooxygenase Constitutively , 1998, Applied and Environmental Microbiology.

[222]  L. Håvarstein.  Increasing competence in the genus Streptococcus , 2010, Molecular microbiology.

[223]  Mat E. Barnet,et al.  A synthetic Escherichia coli predator–prey ecosystem , 2008, Molecular systems biology.

[224]  R. Gardan,et al.  Rgg-Associated SHP Signaling Peptides Mediate Cross-Talk in Streptococci , 2013, PloS one.

[225]  K. Burrage,et al.  Stochastic models for regulatory networks of the genetic toggle switch. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[226]  R. Rahim,et al.  A review on Lactococcus lactis: from food to factory , 2017, Microbial Cell Factories.

[227]  T. Wood,et al.  Indole and 7‐hydroxyindole diminish Pseudomonas aeruginosa virulence , 2008, Microbial biotechnology.

[228]  B. Bassler,et al.  Quorum sensing: cell-to-cell communication in bacteria. , 2005, Annual review of cell and developmental biology.

[229]  Jeff Hasty,et al.  Engineered gene circuits , 2002, Nature.

[230]  Bonnie L. Bassler,et al.  Bacterially Speaking , 2006, Cell.

[231]  G. Braus,et al.  One Juliet and four Romeos: VeA and its methyltransferases , 2015, Front. Microbiol..

[232]  M. Mirzaei,et al.  Ménage à trois in the human gut: interactions between host, bacteria and phages , 2017, Nature Reviews Microbiology.

[233]  Lian-Hui Zhang,et al.  Listening to a new language: DSF-based quorum sensing in Gram-negative bacteria. , 2011, Chemical reviews.

[234]  J. Veening,et al.  Antibiotic-Induced Replication Stress Triggers Bacterial Competence by Increasing Gene Dosage near the Origin , 2014, Cell.

[235]  Ji-Liang Tang,et al.  Diffusible signal factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas maltophilia , 2018, BMC Research Notes.

[236]  Jintae Lee,et al.  Indole as an intercellular signal in microbial communities. , 2010, FEMS microbiology reviews.

[237]  Paul Stoodley,et al.  Targeting microbial biofilms: current and prospective therapeutic strategies , 2017, Nature Reviews Microbiology.

[238]  M. Elowitz,et al.  Synthetic Biology: Integrated Gene Circuits , 2011, Science.

[239]  Christopher A. Voigt,et al.  Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases , 2017, Cell.

[240]  M. Blaser,et al.  Antibiotics in early life alter the murine colonic microbiome and adiposity , 2012, Nature.

[241]  S. Basu,et al.  A synthetic multicellular system for programmed pattern formation , 2005, Nature.

[242]  Matthew R. Bennett,et al.  Emergent genetic oscillations in a synthetic microbial consortium , 2015, Science.

[243]  Ryan A. Kellogg,et al.  Noise Facilitates Transcriptional Control under Dynamic Inputs , 2015, Cell.

[244]  S. Remington,et al.  Chemorepulsion from the Quorum Signal Autoinducer-2 Promotes Helicobacter pylori Biofilm Dispersal , 2015, mBio.

[245]  L. Tsimring,et al.  A synchronized quorum of genetic clocks , 2009, Nature.

[246]  Jasmine Shong,et al.  Quorum sensing-modulated AND-gate promoters control gene expression in response to a combination of endogenous and exogenous signals. , 2014, ACS synthetic biology.

[247]  Karina Bivar Xavier.  Bacterial interspecies quorum sensing in the mammalian gut microbiota. , 2018, Comptes rendus biologies.