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Bonnie L Bassler - One of the best experts on this subject based on the ideXlab platform.
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Bacterial Quorum Sensing in complex and dynamically changing environments
Nature Reviews Microbiology, 2019Co-Authors: Sampriti Mukherjee, Bonnie L BasslerAbstract:Quorum Sensing is a process of bacterial cell-to-cell chemical communication that relies on the production, detection and response to extracellular signalling molecules called autoinducers. Quorum Sensing allows groups of bacteria to synchronously alter behaviour in response to changes in the population density and species composition of the vicinal community. Quorum-Sensing-mediated communication is now understood to be the norm in the bacterial world. Elegant research has defined Quorum-Sensing components and their interactions, for the most part, under ideal and highly controlled conditions. Indeed, these seminal studies laid the foundations for the field. In this Review, we highlight new findings concerning how bacteria deploy Quorum Sensing in realistic scenarios that mimic nature. We focus on how Quorums are detected and how Quorum Sensing controls group behaviours in complex and dynamically changing environments such as multi-species bacterial communities, in the presence of flow, in 3D non-uniform biofilms and in hosts during infection. Most bacteria live in fluctuating environments that can have complex topographies and multiple species present. In this Review, Mukherjee and Bassler discuss how factors such as flow, geometry, biofilms and the presence of the host microbiota influence bacterial Quorum Sensing.
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Surface-attached molecules control Staphylococcus aureus Quorum Sensing and biofilm development
Nature Microbiology, 2017Co-Authors: Aishan Zhao, Ashley Wang, Zachary Z. Brown, Tom W. Muir, Howard A. Stone, Bonnie L BasslerAbstract:Bacteria use a process called Quorum Sensing to communicate and orchestrate collective behaviours, including virulence factor secretion and biofilm formation. Quorum Sensing relies on the production, release, accumulation and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with Quorum-Sensing-manipulation molecules as a method to control collective behaviours. We probe this strategy using Staphylococcus aureus . Pro- and anti-Quorum-Sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviours. We investigate key features of the compounds, linkers and surfaces necessary to appropriately position molecules to interact with cognate receptors and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviours of bacteria on surfaces. Covalent attachment of Quorum-modulating peptides to surfaces can regulate Staphyloccocus aureus biofilm formation.
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Quorum Sensing signal response systems in gram negative bacteria
Nature Reviews Microbiology, 2016Co-Authors: Kai Papenfort, Bonnie L BasslerAbstract:Bacteria use Quorum Sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum Sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of Quorum Sensing signal-response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host-microbial associations and antibacterial therapy.
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Quorum Sensing signal–response systems in Gram-negative bacteria
Nature Reviews Microbiology, 2016Co-Authors: Kai Papenfort, Bonnie L BasslerAbstract:Bacteria use Quorum Sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum Sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of Quorum Sensing signal–response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host–microbial associations and antibacterial therapy. Quorum Sensing is used to control the behaviour of bacterial communities. In this Review, Papenfort and Bassler highlight recent discoveries about Quorum Sensing in Gram-negative bacteria, such as novel autoinducers and signalling networks that promote communication that ranges from intra-species to inter-kingdom. Quorum Sensing is a cell–cell communication process that enables bacteria to obtain information about cell density and species composition of the vicinal community and adjust their gene expression profiles accordingly. Quorum Sensing involves the production, release and detection of extracellular signalling molecules known as autoinducers. Group-wide detection of autoinducers enables bacteria to collectively execute behaviours. Autoinducers are small molecules that control Quorum Sensing. In Gram-negative bacteria, autoinducers are often produced from S -adenosylmethionine (SAM). Autoinducers interact with specific receptors to elicit behaviours that are controlled by Quorum Sensing. Quorum Sensing receptors are either membrane-bound histidine sensor kinases or cytoplasmic transcription factors. Autoinduction occurs when the detection of autoinducers induces the increased production of the same autoinducer molecule, forming a feed-forward regulatory loop. Other features, such as positive and negative feedback loops and small regulatory RNAs, optimize the integration of the autoinducer-encoded information and provide ideal Quorum Sensing dynamics. Signal integration is a process that takes place in most Gram-negative bacteria when several autoinducers and receptors work in parallel, or in series, to synchronize functions that are controlled by Quorum Sensing. Processes such as bioluminescence, the production of virulence factors and the formation of biofilms are controlled by Quorum Sensing. Quorum Sensing shapes the composition of microbial communities. For example, bacterial species in the human gut microbiota produce and respond to autoinducers. There is increasing evidence that Quorum Sensing controls key physiological processes in the gut and may affect the virulence programmes of invading pathogens. Host cells are also known to produce autoinducer mimics. Synthetic Quorum Sensing modulators are molecules that agonize or antagonize Quorum Sensing and they are being developed as anti-virulence medicines. Distinct from traditional antibiotics, Quorum Sensing modulators do not affect the growth of pathogenic bacteria, but rather, disrupt their virulence programmes.
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A Quorum-Sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation
Proceedings of the National Academy of Sciences, 2013Co-Authors: C. T. O'loughlin, L. C. Miller, Albert Siryaporn, Martin F. Semmelhack, Karla Drescher, Bonnie L BasslerAbstract:Quorum Sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling Quorum-Sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses Quorum Sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa Quorum-Sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.
Juan E Gonzalez - One of the best experts on this subject based on the ideXlab platform.
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role of Quorum Sensing in sinorhizobium meliloti alfalfa symbiosis
Journal of Bacteriology, 2009Co-Authors: Nataliya Gurich, Juan E GonzalezAbstract:The ExpR/Sin Quorum-Sensing system of the gram-negative soil bacterium Sinorhizobium meliloti plays an important role in the establishment of symbiosis with its host plant Medicago sativa. A mutant unable to produce autoinducer signal molecules (sinI) is deficient in its ability to invade the host, but paradoxically, a strain lacking the Quorum-Sensing transcriptional regulator ExpR is as efficient as the wild type. We compared the whole-genome expression profile of the wild-type strain with strains missing one of the Quorum-Sensing regulatory components to identify genes controlled by the ExpR/Sin system throughout the different phases of the bacterial growth cycle, as well as in planta. Our analyses revealed that ExpR is a highly versatile regulator with a unique ability to show different regulatory capabilities in the presence or absence of an autoinducer. In addition, this study provided us with insight into the plant invasion defect displayed by the autoinducer mutant. We also discovered that the ExpR/Sin Quorum-Sensing system is repressed after plant invasion. Therefore, Quorum Sensing plays a crucial role in the regulation of many cell functions that ensures the successful invasion of the host and is inactivated once symbiosis is established.
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regulation of motility by the expr sin Quorum Sensing system in sinorhizobium meliloti
Journal of Bacteriology, 2008Co-Authors: Hanh H Hoang, Nataliya Gurich, Juan E GonzalezAbstract:A successful symbiotic relationship between Sinorhizobium meliloti and its host Medicago sativa (alfalfa) depends on several signaling mechanisms, such as the biosynthesis of exopolysaccharides (EPS) by S. meliloti. Previous work in our laboratory has shown that a Quorum-Sensing mechanism controls the production of the symbiotically active EPS II. Recent microarray analysis of the whole-genome expression profile of S. meliloti reveals that the ExpR/Sin Quorum-Sensing system regulates additional physiological processes that include low-molecular-weight succinoglycan production, nitrogen utilization, metal transport, motility, and chemotaxis. Nearly half of the flagellar genes and their dependence on Quorum Sensing are prominently displayed in our microarray analyses. We extend those observations in this work and confirm the findings by real-time PCR expression analysis of selected genes, including the flaF, flbT, flaC, cheY1, and flgB genes, involved in motility and chemotaxis. These genes code for regulators of flagellum synthesis, the chemotactic response, or parts of the flagellar apparatus. Gene expression analyses and visualization of flagella by electron microscopy performed at different points in the growth phase support our proposed model in which Quorum Sensing downregulates motility in S. meliloti. We demonstrate that the ExpR/Sin Quorum-Sensing system controls motility gene expression through the VisN/VisR/Rem relay. We also show that the ExoS-dependent two-component system suppresses motility gene expression through VisN and Rem in parallel to Quorum Sensing. This study contributes to our understanding of the mechanisms that govern motility in S. meliloti.
Paul Williams - One of the best experts on this subject based on the ideXlab platform.
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Significant immunomodulatory effects of Pseudomonas aeruginosa Quorum-Sensing signal molecules: possible link in human sepsis
Clinical Science, 2008Co-Authors: Pisake Boontham, Miguel Cámara, Paul Williams, Adrian R. Robins, Palanichamy Chandran, David Pritchard, Suebwong Chuthapisith, Alasdair Mckechnie, Brian J. Rowlands, Oleg EreminAbstract:Pathogenic bacteria use Quorum-Sensing signal molecules to coordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of Quorum-Sensing signal molecules. We have examined the impact of these molecules on normal human immune function in vitro, and compared this with immune changes in patients with sepsis where Quorum-Sensing signal molecules were detected in patients' sera. Quorum-Sensing signal molecules inhibited normal dentritic cell and T cell activation and proliferation, down-regulated expression of co-stimulatory molecules on dendritic cells; in mixed lymphocyte dendritic cell reactions (MLDCRs), secretion of IL-4 and IL-10 was enhanced, but TNF-α, IFN-γ and IL-6 was reduced. Quorum-Sensing signal molecules induced apoptosis in dendritic cells and CD4+ cells, but not CD8+ cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4+ Th 1}/Th 2} apoptotic rate, and modified Th 1}/Th 2} cytokine profiles in mixed lymphocyte dendritic cell reactions were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of Quorum-Sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that Quorum-Sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis.
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look who s talking communication and Quorum Sensing in the bacterial world
Philosophical Transactions of the Royal Society B, 2007Co-Authors: Paul Williams, Klaus Winzer, Weng C Chan, Miguel CámaraAbstract:For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term ‘Quorum Sensing’ has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum Sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of Quorum Sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of Quorum Sensing-dependent genes. Quorum Sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum Sensing also crosses the prokaryotic–eukaryotic boundary since Quorum Sensing-dependent signalling can be exploited or inactivated by both plants and mammals.
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Quorum Sensing in Vibrio cholerae
Nature Genetics, 2002Co-Authors: Miguel Cámara, Andrea Hardman, Paul Williams, Debra MiltonAbstract:Bacteria can communicate with members of their own species and others to coordinate their behavior in response to cell density. This phenomenon, known as Quorum Sensing, relies on the production and Sensing of one or more secreted signal molecules. A recent study identifies a complex Quorum Sensing network in the human pathogen Vibrio cholerae .
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Quorum Sensing as an integral component of gene regulatory networks in Gram-negative bacteria.
Current opinion in microbiology, 2001Co-Authors: Helen Withers, Simon Swift, Paul WilliamsAbstract:Bacterial cell-to-cell communication (Quorum Sensing) relies upon the interaction of a small diffusible signal molecule with a sensor or transcriptional activator to couple gene expression with cell population density. In Gram-negative bacteria, it is now clear that N-acylhomoserine lactones bind directly to LuxR homologues and can be synthesized via one of three unrelated bacterial protein families and by transgenic plants. New chemical classes of signal molecules have been identified, some of which exhibit crosstalk with N-acylhomoserine-lactone-mediated Quorum Sensing. As the determinant of cell population density, Quorum Sensing is emerging as an integral component of bacterial global gene regulatory networks responsible for facilitating bacterial adaptation to environmental stress. N-acylhomoserine lactones are produced during experimental animal and human infections, and a function beyond Quorum Sensing has been suggested by their intrinsic immunomodulatory and pharmacological activities.
E P Greenberg - One of the best experts on this subject based on the ideXlab platform.
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a new class of homoserine lactone Quorum Sensing signals
Nature, 2008Co-Authors: Amy L Schaefer, E P Greenberg, Colin M Oliver, Yasuhiro Oda, Jean J Huang, Gili Bittanbanin, Caroline M Peres, Silke Schmidt, Katarina Juhaszova, Janice R SufrinAbstract:Quorum Sensing is a term used to describe cell-to-cell communication that allows cell-density-dependent gene expression. Many bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL Quorum-Sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. Here we show that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium sp. and Silicibacter pomeroyi. This discovery extends the range of possibilities for acyl-HSL Quorum Sensing and raises fundamental questions about Quorum Sensing within the context of environmental signalling.
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qscr a modulator of Quorum Sensing signal synthesis and virulence in pseudomonas aeruginosa
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Sudha Chugani, Marvin Whiteley, Kimberly M Lee, E P Greenberg, David A Dargenio, Colin ManoilAbstract:The opportunistic pathogenic bacterium Pseudomonas aeruginosa uses Quorum-Sensing signaling systems as global regulators of virulence genes. There are two Quorum-Sensing signal receptor and signal generator pairs, LasR–LasI and RhlR–RhlI. The recently completed P. aeruginosa genome-sequencing project revealed a gene coding for a homolog of the signal receptors, LasR and RhlR. Here we describe a role for this gene, which we call qscR . The qscR gene product governs the timing of Quorum-Sensing-controlled gene expression and it dampens virulence in an insect model. We present evidence that suggests the primary role of QscR is repression of lasI . A qscR mutant produces the LasI-generated signal prematurely, and this results in premature transcription of a number of Quorum-Sensing-regulated genes. When fed to Drosophila melanogaster , the qscR mutant kills the animals more rapidly than the parental P. aeruginosa . The repression of lasI by QscR could serve to ensure that Quorum-Sensing-controlled genes are not activated in environments where they are not useful.
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regulation of gene expression by cell to cell communication acyl homoserine lactone Quorum Sensing
Annual Review of Genetics, 2001Co-Authors: Clay Fuqua, Matthew R Parsek, E P GreenbergAbstract:Quorum Sensing is an example of community behavior prevalent among diverse bacterial species. The term "Quorum Sensing" describes the ability of a microorganism to perceive and respond to microbial population density, usually relying on the production and subsequent response to diffusible signal molecules. A significant number of gram-negative bacteria produce acylated homoserine lactones (acyl-HSLs) as signal molecules that function in Quorum Sensing. Bacteria that produce acyl-HSLs can respond to the local concentration of the signaling molecules, and high population densities foster the accumulation of inducing levels of acyl-HSLs. Depending upon the bacterial species, the physiological processes regulated by Quorum Sensing are extremely diverse, ranging from bioluminescence to swarming motility. Acyl-HSL Quorum Sensing has become a paradigm for intercellular signaling mechanisms. A flurry of research over the past decade has led to significant understanding of many aspects of Quorum Sensing including the synthesis of acyl-HSLs, the receptors that recognize the acyl-HSL signal and transduce this information to the level of gene expression, and the interaction of these receptors with the transcriptional machinery. Recent studies have begun to integrate acyl-HSL Quorum Sensing into global regulatory networks and establish its role in developing and maintaining the structure of bacterial communities.
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identification of genes controlled by Quorum Sensing in pseudomonas aeruginosa
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Marvin Whiteley, Kimberly M Lee, E P GreenbergAbstract:Bacteria communicate with each other to coordinate expression of specific genes in a cell density-dependent fashion, a phenomenon called Quorum Sensing and response. Although we know that Quorum Sensing via acyl-homoserine lactone (HSL) signals controls expression of several virulence genes in the human pathogen Pseudomonas aeruginosa, the number and types of genes controlled by Quorum Sensing have not been studied systematically. We have constructed a library of random insertions in the chromosome of a P. aeruginosa acyl-HSL synthesis mutant by using a transposon containing a promoterless lacZ. This library was screened for acyl-HSL induction of lacZ. Thirty-nine Quorum Sensing-regulated genes were identified. The genes were organized into classes depending on the pattern of regulation. About half of the genes appear to be in seven operons, some seem organized in large patches on the genome. Many of the Quorum Sensing-regulated genes code for putative virulence factors or production of secondary metabolites. Many of the genes identified showed a high level of induction by acyl-HSL signaling.
Melissa B Miller - One of the best experts on this subject based on the ideXlab platform.
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csra and three redundant small rnas regulate Quorum Sensing in vibrio cholerae
Molecular Microbiology, 2005Co-Authors: Derrick H Lenz, Melissa B Miller, Jun Zhu, Rahul V Kulkarni, Bonnie L BasslerAbstract:Bacteria communicate using a process called Quorum Sensing which involves production, secretion and detection of signalling molecules called autoinducers. Quorum Sensing allows populations of bacteria to simultaneously regulate gene expression in response to changes in cell density. The human pathogen, Vibrio cholerae, uses a Quorum-Sensing circuit composed of parallel systems that transduce information through four redundant regulatory small RNAs (sRNAs) called Quorum regulatory RNAs (Qrr) to control the expression of numerous genes, most notably those required for virulence. We show that the VarS/VarA two-component sensory system comprises an additional regulatory input controlling Quorum-Sensing-dependent gene expression in V. cholerae. VarS/VarA controls transcription of three previously unidentified small regulatory RNAs (sRNAs) that are similar to the sRNAs CsrB and CsrC of Escherichia coli. The three V. cholerae sRNAs, which we name CsrB, CsrC and CsrD, act redundantly to control the activity of the global regulatory protein, CsrA. The VarS/VarA-CsrA/BCD system converges with the V. cholerae Quorum-Sensing systems to regulate the expression of the Qrr sRNAs, and thus, the entire Quorum-Sensing regulon.
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parallel Quorum Sensing systems converge to regulate virulence in vibrio cholerae
Cell, 2002Co-Authors: Melissa B Miller, Derrick H Lenz, Karen Skorupski, Ronald K Taylor, Bonnie L BasslerAbstract:The marine bacterium Vibrio harveyi possesses two Quorum Sensing systems (System 1 and System 2) that regulate bioluminescence. Although the Vibrio cholerae genome sequence reveals that a V. harveyi-like System 2 exists, it does not predict the existence of a V. harveyi-like System 1 or any obvious Quorum Sensing-controlled target genes. In this report we identify and characterize the genes encoding an additional V. cholerae autoinducer synthase and its cognate sensor. Analysis of double mutants indicates that a third as yet unidentified sensory circuit exists in V. cholerae. This Quorum Sensing apparatus is unusually complex, as it is composed of at least three parallel signaling channels. We show that in V. cholerae these communication systems converge to control virulence.
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Quorum Sensing in bacteria
Annual Review of Microbiology, 2001Co-Authors: Melissa B Miller, Bonnie L BasslerAbstract:▪ Abstract Quorum Sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum Sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use Quorum Sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. In general, Gram-negative bacteria use acylated homoserine lactones as autoinducers, and Gram-positive bacteria use processed oligo-peptides to communicate. Recent advances in the field indicate that cell-cell communication via autoinducers occurs both within and between bacterial species. Furthermore, there is mounting data suggesting that ba...
