Supporting (BibTeX).bib

@Article{DeSordi2009,
author = {De Sordi, L and Mühlschlegel, FA}, 
title = {Quorum sensing and fungal-bacterial interactions in {\emph{Candida albicans:}} a communicative network regulating microbial coexistence and virulence.}, 
journal = {FEMS Yeast Res}, 
volume = {9}, 
number = {7}, 
pages = {990--999}, 
year = {2009}, 
abstract = {Microorganisms have evolved a complex signature of communication termed quorum sensing (QS), which is based on the exchange and sensing of low molecular- weight signal compounds. The ability to communicate within the microbial population gives the advantage to coordinate a groups behaviour leading to a higher fitness in the environment. The polymorphic fungus Candida albicans is an opportunistic human pathogen able to regulate virulence traits through the production of at least two QS signal molecules: farnesol and tyrosol. The ability to adopt multiple morphotypes and form biofilms on infected surfaces are the most important pathogenic characteristics regulated by QS and are of clinical relevance. In fact, traditional antimicrobial approaches are often ineffective towards these characteristics. Moreover, the intimate association between C. albicans and other pathogens, such as Pseudomonas aeruginosa, increases the complexity of the infection system. This review outlines the current knowledge on fungal QS and fungal-bacterial interactions emphasizing on C. albicans. Further investigations need to concentrate on the molecular mechanisms and the genetic regulation of these phenomena in order to identify putative novel therapeutic options.}, 
location = {Department of Biosciences, University of Kent, Canterbury, UK.}, }

@Article{Donabedian2003,
author = {Donabedian, H}, 
title = {Quorum sensing and its relevance to infectious diseases.}, 
journal = {J Infect}, 
volume = {46}, 
number = {4}, 
pages = {207--214}, 
year = {2003}, 
abstract = {Quorum sensing allows bacteria to detect the density of their own species and alter their metabolism to take advantage of this density. Quorum sensing is used by a wide variety of bacteria including human pathogens. Quorum sensing genes are important for the pathogenic potential of Pseudomonas aeruginosa and Staphylococcus aureus, as well as other invasive bacteria. An understanding of quorum sensing may lead to new therapeutic strategies.}, 
location = {Departments of Internal Medicine, Microbiology and Immunology, Division of Infectious Diseases, Medical College of Ohio, Toledo, OH 43614, USA. h.donabedian@mco.edu}, }

@Article{GarcíaReyes2020,
author = {García-Reyes, S and Soberón-Chávez, G and Cocotl-Yanez, M}, 
title = {The third quorum-sensing system of {\emph{Pseudomonas aeruginosa:}} Pseudomonas quinolone signal and the enigmatic PqsE protein.}, 
journal = {J Med Microbiol}, 
volume = {69}, 
number = {1}, 
pages = {25--34}, 
year = {2020}, 
abstract = {Pseudomonas aeruginosa is an opportunistic pathogen that produces several virulence factors such as lectin A, pyocyanin, elastase and rhamnolipids. These compounds are controlled transcriptionally by three quorum-sensing circuits, two based on the synthesis and detection of N-acyl-homoserine-lactone termed the Las and Rhl system and a third system named the Pseudomonas quinolone signal (PQS) system, which is responsible for generating 2-alkyl-4(1 h)-quinolones (AQs). The transcriptional regulator called PqsR binds to the promoter of pqsABCDE in the presence of PQS or HHQ creating a positive feedback-loop. PqsE, encoded in the operon for AQ synthesis, is a crucial protein for pyocyanin production, activating the Rhl system by a still not fully understood mechanism. In turn, the regulation of the PQS system is modulated by Las and Rhl systems, which act positively and negatively, respectively. This review focuses on the PQS system, from its discovery to its role in Pseudomonas pathogenesis, such as iron depletion and pyocyanin synthesis that involves the PqsE protein - an intriguing player of this system.}, 
location = {Departamento de Biología molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Apdo Postal 70228, C.P. 04510, Ciudad de México, Mexico. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México. Av. Universidad 3000, Cd. Universitaria, C.P. 04510, Coyoacán, Ciudad de México, Mexico.}, }

@Article{Heurlier2006,
author = {Heurlier, K and Dénervaud, V and Haas, D}, 
title = {Impact of quorum sensing on fitness of {\emph{Pseudomonas aeruginosa.}}}, 
journal = {Int J Med Microbiol}, 
volume = {296}, 
number = {2-3}, 
pages = {93--102}, 
year = {2006}, 
abstract = {In Pseudomonas aeruginosa, cell-cell communication based on N-acyl-homoserine lactone (AHL) signal molecules (termed quorum sensing) is known to control the production of extracellular virulence factors. Hence, in pathogenic interactions with host organisms, the quorum-sensing (QS) machinery can confer a selective advantage on P. aeruginosa. However, as shown by transcriptomic and proteomic studies, many intracellular metabolic functions are also regulated by quorum sensing. Some of these serve to regenerate the AHL precursors methionine and S-adenosyl-methionine and to degrade adenosine via inosine and hypoxanthine. The fact that a significant percentage of clinical and environmental isolates of P. aeruginosa is defective for QS because of mutation in the major QS regulatory gene lasR, raises the question of whether the QS machinery can have a negative impact on the organism's fitness. In vitro, lasR mutants have a higher probability to escape lytic death in stationary phase under alkaline conditions than has the QS-proficient wild type. Similar selective forces might also operate in natural environments.}, 
location = {Institute of Infection, Immunity, and Inflammation, Centre for Biomolecular Sciences, Nottingham University, Nottingham NG7 2RD, UK.}, }

@Article{Jakobsen2013,
author = {Jakobsen, TH and Bjarnsholt, T and Jensen, PØ and Givskov, M and Høiby, N}, 
title = {Targeting quorum sensing in {\emph{Pseudomonas aeruginosa}} biofilms: current and emerging inhibitors.}, 
journal = {Future Microbiol}, 
volume = {8}, 
number = {7}, 
pages = {901--921}, 
year = {2013}, 
abstract = {Bacterial resistance to conventional antibiotics combined with an increasing acknowledgement of the role of biofilms in chronic infections has led to a growing interest in new antimicrobial strategies that target the biofilm mode of growth. In the aggregated biofilm mode, cell-to-cell communication systems involved in the process known as quorum sensing regulate coordinated expression of virulence with immune shielding mechanisms and antibiotic resistance. For two decades, the potential of interference with quorum sensing by small chemical compounds has been investigated with the aim of developing alternative antibacterial strategies. Here, we review state of the art research of quorum sensing inhibitors against the opportunistic human pathogen Pseudomonas aeruginosa, which is found in a number of biofilm-associated infections and identified as the predominant organism infecting the lungs of cystic fibrosis patients.}, 
location = {Costerton Biofilm Center, Department of International Health, Immunology \& Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark.}, }

@Article{Juhas2005,
author = {Juhas, M and Eberl, L and Tümmler, B}, 
title = {Quorum sensing: the power of cooperation in the world of {\emph{Pseudomonas.}}}, 
journal = {Environ Microbiol}, 
volume = {7}, 
number = {4}, 
pages = {459--471}, 
year = {2005}, 
abstract = {Work over the past few years has provided evidence that quorum sensing is a generic regulatory mechanism that allows bacteria to launch a unified, coordinated response in a population density-dependent manner to accomplish tasks which would be difficult, if not impossible, to achieve for a single bacterial cell. Quorum sensing systems are widespread among pseudomonads and the one of the human opportunistic pathogen Pseudomonas aeruginosa belongs to the most extensively studied cell-to-cell communication systems. In this organism, quorum sensing is highly complex and is made up of two interlinked N-acyl homoserine lactone (AHL)-dependent regulatory circuits, which are further modulated by a non-AHL-related signal molecule and numerous regulators acting both at the transcriptional and post-transcriptional level. This genetic complexity may be one of the key elements responsible for the tremendous environmental versatility of P. aeruginosa. Work of the past few years showed that quorum sensing is essential for the expression of a battery of virulence factors as well as for biofilm formation in P. aeruginosa and thus represents an attractive target for the design of novel drugs for the treatment of P. aeruginosa infections. Furthermore, the cell-to-cell communication ability was also demonstrated in a number of additional pseudomonads.}, 
location = {University of Oxford, Nuffield Department of Clinical Laboratory Sciences, Headington, Oxford OX3 9DU, UK. juhas_mario@pobox.sk}, }

@Article{LeBerre2006,
author = {Le Berre, R and Faure, K and Nguyen, S and Pierre, M and Ader, F and Guery, B}, 
title = {[Quorum sensing: a new clinical target for {\emph{Pseudomonas aeruginosa}}?].}, 
journal = {Med Mal Infect}, 
volume = {36}, 
number = {7}, 
pages = {349--357}, 
year = {2006}, 
abstract = {Pseudomonas aeruginosa is an opportunistic bacteria causing a wide variety of infections. The bacterial virulence depends on a large panel of cell-associated and extracellular factors. Quorum sensing (QS) allows cell-to-cell communication: sensing the environment, this system coordinates the expression of various genes within the bacterial population. QS is based on an interaction between a small diffusible molecule, an acylhomoserine lactone (AHL), and a transcriptionnal activator. Two QS systems, the las and rhl systems, have been identified in P. aeruginosa. The las system associates the transcriptionnal activator protein LasR and LasI responsible for the synthesis of a specific AHL: C12-HSL. This system was shown to activate the expression of a large number of virulence factors. Similarly, the rhl system associates the transcriptionnal activator protein RhlR with RhlI, which is responsible for the synthesis of another AHL: C4-HSL. Synthesis and secretion of a number of virulence factors are controlled by QS. Utilization of different animals models showed the crucial role of QS in the pathogenesis of P. aeruginosa infections. The discovery of QS has given a new opportunity to treat bacterial infection by another means than growth inhibition. New drugs inhibiting QS were recently discovered: furanone compounds can repress a large number of QS-regulated genes, including numerous P. aeruginosa virulence factor genes. Furanone administration to mice infected with P. aeruginosa significantly reduced lung bacterial load compared with the control group.}, 
location = {Laboratoire de recherche en pathologie infectieuse, EA 2689, faculté de médecine de Lille, 59045 Lille, France. rozenn2@libertysurf.fr}, }

@Article{Papaioannou2013,
author = {Papaioannou, E and Utari, PD and Quax, WJ}, 
title = {Choosing an appropriate infection model to study quorum sensing inhibition in {\emph{Pseudomonas}} infections.}, 
journal = {Int J Mol Sci}, 
volume = {14}, 
number = {9}, 
pages = {19309--19340}, 
year = {2013}, 
abstract = {Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review.}, 
location = {Department of Pharmaceutical Biology, University of Groningen, Groningen 9713AV, The Netherlands. w.j.quax@rug.nl.}, }

@Article{Proctor2020,
author = {Proctor, CR and McCarron, PA and Ternan, NG}, 
title = {Furanone quorum-sensing inhibitors with potential as novel therapeutics against {\emph{Pseudomonas aeruginosa.}}}, 
journal = {J Med Microbiol}, 
volume = {69}, 
number = {2}, 
pages = {195--206}, 
year = {2020}, 
abstract = {Micro-organisms use quorum sensing (QS), a cell density-dependent process, to communicate. This QS mode of interchange leads to the production of a variety of virulence factors, co-ordination of complex bacterial behaviours, such as swarming motility, degradation of host tissue and biofilm formation. QS is implicated in numerous human infections and consequently researchers have sought ways of effectively inhibiting the process in pathogenic bacteria. Two decades ago, furanones were the first class of chemical compounds identified as Pseudomonas aeruginosa QS inhibitors (QSIs). P. aeruginosa is a ubiquitous organism, capable of causing a wide range of infections in humans, including eye and ear infections, wound infections and potentially fatal bacteraemia and thus novel treatments against this organism are greatly needed. This review provides a brief background on QS and the use of furanones as QSIs. Based on the effectiveness of action, both in vivo and in vitro, we will explore the use of furanones as potential antimicrobial therapeutics and conclude with open questions.}, 
location = {Nutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Northern Ireland, UK. School of Pharmacy and Pharmaceutical Sciences, Ulster University, Northern Ireland, UK. School of Pharmacy and Pharmaceutical Sciences, Ulster University, Northern Ireland, UK. Nutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Northern Ireland, UK.}, }

@Article{Reuter2016,
author = {Reuter, K and Steinbach, A and Helms, V}, 
title = {Interfering with Bacterial Quorum Sensing.}, 
journal = {Perspect Medicin Chem}, 
volume = {8}, 
pages = {1--15}, 
year = {2016}, 
abstract = {Quorum sensing (QS) describes the exchange of chemical signals in bacterial populations to adjust the bacterial phenotypes according to the density of bacterial cells. This serves to express phenotypes that are advantageous for the group and ensure bacterial survival. To do so, bacterial cells synthesize autoinducer (AI) molecules, release them to the environment, and take them up. Thereby, the AI concentration reflects the cell density. When the AI concentration exceeds a critical threshold in the cells, the AI may activate the expression of virulence-associated genes or of luminescent proteins. It has been argued that targeting the QS system puts less selective pressure on these pathogens and should avoid the development of resistant bacteria. Therefore, the molecular components of QS systems have been suggested as promising targets for developing new anti-infective compounds. Here, we review the QS systems of selected gram-negative and gram-positive bacteria, namely, Vibrio fischeri, Pseudomonas aeruginosa, and Staphylococcus aureus, and discuss various antivirulence strategies based on blocking different components of the QS machinery.}, 
location = {Center for Bioinformatics, Saarland University, Saarbrücken, Germany.; Saarbrücken Graduate School of Computer Science, Saarland University, Saarbrücken, Germany. Department of Drug Design and Optimization, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Saarbrücken, Germany. Center for Bioinformatics, Saarland University, Saarbrücken, Germany.}, }

@Article{Roy2011,
author = {Roy, V and Adams, BL and Bentley, WE}, 
title = {Developing next generation antimicrobials by intercepting AI-2 mediated quorum sensing.}, 
journal = {Enzyme Microb Technol}, 
volume = {49}, 
number = {2}, 
pages = {113--123}, 
year = {2011}, 
abstract = {Bacteria have been evolving antibiotic resistance since their discovery in the early twentieth century. Most new antibiotics are derivatives of older generations and there are now bacteria that are virtually resistant to almost all antibiotics. This poses a global threat to human health and has been classified as a clinical , which has necessitated research into new antimicrobials that inhibit bacterial virulence while minimizing selective pressures that lead to the emergence of resistant strains. Quorum sensing (QS), the process of population dependent bacterial cell-cell signaling, can accelerate bacterial virulence and is an increasingly interesting target for developing next generation antimicrobials. Most QS inhibitors target species-specific signals, such as acylhomoserine lactones (AHLs) and oligopeptides. Methodologies for intercepting the cross-species signal, autoinducer-2 (AI-2), have only recently emerged. We review these strategies to prevent the relay of the AI-2 signal amongst pathogens, including Escherichia coli, Salmonella enterica serovar Typhimurium, Vibrio cholerae and Pseudomonas aeruginosa. Inhibition mechanisms are categorized based on the target (i.e., enzymes for signal generation, the signal molecule itself, or the various components of the signal transduction process). The universal nature of the AI-2 signal imparts on its inhibitors the potential for broad spectrum use.}, 
location = {Graduate Program in Molecular and Cell Biology, University of Maryland, College Park, MD 20742, USA.}, }

@Article{Rutherford2012,
author = {Rutherford, ST and Bassler, BL}, 
title = {Bacterial quorum sensing: its role in virulence and possibilities for its control.}, 
journal = {Cold Spring Harb Perspect Med}, 
volume = {2}, 
number = {11}, 
pages = {a012427}, 
year = {2012}, 
abstract = {Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.}, 
location = {Department of Molecular Biology, Princeton University, New Jersey 08544, USA.}, }

@Article{Schuster2013,
author = {Schuster, M and Sexton, DJ and Diggle, SP and Greenberg, EP}, 
title = {Acyl-homoserine lactone quorum sensing: from evolution to application.}, 
journal = {Annu Rev Microbiol}, 
volume = {67}, 
pages = {43--63}, 
year = {2013}, 
abstract = {Quorum sensing (QS) is a widespread process in bacteria that employs autoinducing chemical signals to coordinate diverse, often cooperative activities such as bioluminescence, biofilm formation, and exoenzyme secretion. Signaling via acyl-homoserine lactones is the paradigm for QS in Proteobacteria and is particularly well understood in the opportunistic pathogen Pseudomonas aeruginosa. Despite thirty years of mechanistic research, empirical studies have only recently addressed the benefits of QS and provided support for the traditional assumptions regarding its social nature and its role in optimizing cell-density-dependent group behaviors. QS-controlled public-goods production has served to investigate principles that explain the evolution and stability of cooperation, including kin selection, pleiotropic constraints, and metabolic prudence. With respect to medical application, appreciating social dynamics is pertinent to understanding the efficacy of QS-inhibiting drugs and the evolution of resistance. Future work will provide additional insight into the foundational assumptions of QS and relate laboratory discoveries to natural ecosystems.}, 
location = {Department of Microbiology, Oregon State University, Corvallis, Oregon 97331; email: martin.schuster@oregonstate.edu , sextond@science.oregonstate.edu.}, }

@Article{Soukarieh2018,
author = {Soukarieh, F and Williams, P and Stocks, MJ and Cámara, M}, 
title = {{\emph{Pseudomonas aeruginosa}} Quorum Sensing Systems as Drug Discovery Targets: Current Position and Future Perspectives.}, 
journal = {J Med Chem}, 
volume = {61}, 
number = {23}, 
pages = {10385--10402}, 
year = {2018}, 
abstract = {Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multidrug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the severity of this crisis and implemented action plans to contain its adverse consequences and prolong the utility of conventional antibiotics. Hence, there is a pressing need for new classes of antibacterial agents with novel modes of action. Quorum sensing (QS), a communication system employed by bacterial populations to coordinate virulence gene expression, is a potential target that has been intensively investigated over the past decade. This Perspective will focus on recent advances in targeting the three main quorum sensing systems ( las, rhl, and pqs) of a major opportunistic human pathogen, Pseudomonas aeruginosa, and will specifically evaluate the medicinal chemistry strategies devised to develop QS inhibitors from a drug discovery perspective.}, 
location = {School of Life Sciences, Centre for Biomolecular Sciences , University of Nottingham , Nottingham , NG7 2RD , U.K. School of Pharmacy, Centre for Biomolecular Sciences , University of Nottingham , Nottingham , NG7 2RD , U.K. School of Life Sciences, Centre for Biomolecular Sciences , University of Nottingham , Nottingham , NG7 2RD , U.K.}, }

@Article{Tateda2005,
author = {Tateda, K}, 
title = {[{\emph{Pseudomonas aeruginosa}} infection and the quorum-sensing mechanism].}, 
journal = {Nihon Naika Gakkai Zasshi}, 
volume = {94}, 
number = {5}, 
pages = {999--1004}, 
year = {2005}, }

@Article{Welsh2016,
author = {Welsh, MA and Blackwell, HE}, 
title = {Chemical probes of quorum sensing: from compound development to biological discovery.}, 
journal = {FEMS Microbiol Rev}, 
volume = {40}, 
number = {5}, 
pages = {774--794}, 
year = {2016}, 
abstract = {Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a method of cell-cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues.}, 
location = {Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA. Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA blackwell@chem.wisc.edu.}, }

@Article{Williams2007,
author = {Williams, P and Winzer, K and Chan, WC and Cámara, M}, 
title = {Look who's talking: communication and quorum sensing in the bacterial world.}, 
journal = {Philos Trans R Soc Lond B Biol Sci}, 
volume = {362}, 
number = {1483}, 
pages = {1119--1134}, 
year = {2007}, 
abstract = {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.}, 
location = {Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, School of Molecular Medical Sciences, University of Nottingham, Nottingham NG7 2RD, UK. paul.williams@nottingham.ac.uk}, }

@Article{Winzer2001,
author = {Winzer, K and Williams, P}, 
title = {Quorum sensing and the regulation of virulence gene expression in pathogenic bacteria.}, 
journal = {Int J Med Microbiol}, 
volume = {291}, 
number = {2}, 
pages = {131--143}, 
year = {2001}, 
abstract = {For many pathogens, the outcome of the interaction between host and bacterium is strongly affected by the bacterial population size. Coupling the production of virulence factors with cell population density ensures that the mammalian host lacks sufficient time to mount an effective defence against consolidated attack. Such a strategy depends on the ability of an individual bacterial cell to sense other members of the same species and in response, differentially express specific sets of genes. Such cell-cell communication is called  and involves the direct or indirect activation of a response regulator by a small diffusible signal molecule. A number of chemically distinct quorum-sensing signal molecules have been described including the N-acyl-L-homoserine lactones (AHLs) in Gram-negative bacteria and post-translationally modified peptides in Gram-positive bacteria. For example, the human pathogens Pseudomonas aeruginosa and Staphylococcus aureus employ AHLs and peptides, respectively, to control the expression of multiple virulence genes in concert with cell population density. Apart from their role in signal transduction, certain quorum-sensing signal molecules, notably N-(3-oxododecanoyl)homoserine lactone, possess intrinsic pharmacological and immunomodulatory activities such that they may function as virulence determinants per se. While quorum-sensing signal molecules have been detected in tissues in experimental animal model and human infections, the mutation of genes involved in either quorum-sensing signal generation or signal transduction frequently results in the attenuation of virulence. Thus, interference with quorum sensing represents a promising strategy for the therapeutic or prophylactic control of infection.}, 
location = {Institute of Infections \& Immunity, Queen's Medical Centre, University of Nottingham, UK.}, }

@Article{Yong2013,
author = {Yong, YC and Zhong, JJ}, 
title = {Impacts of quorum sensing on microbial metabolism and human health.}, 
journal = {Adv Biochem Eng Biotechnol}, 
volume = {131}, 
pages = {25--61}, 
year = {2013}, 
abstract = {Bacteria were considered to be lonely `mutes' for hundreds of years. However, recently it was found that bacteria usually coordinate their behaviors at the population level by producing (speaking), sensing (listening), and responding to small signal molecules. This so-called quorum sensing (QS) regulation enables bacteria to live in a `society' with cell-cell communication and controls many important bacterial behaviors. In this chapter, QS systems and their signal molecules for Gram-negative and Gram-positive bacteria are introduced. Most interestingly, QS regulates the important bacterial behaviors such as metabolism and pathogenesis. QS-regulated microbial metabolism includes antibiotic synthesis, pollutant biodegradation, and bioenergy production, which are very relevant to human health. QS is also well-known for its involvement in bacterial pathogenesis, such as iin nfections by Pseudomonas aeruginosa and Staphylococcus aureus. Novel disease diagnosis strategies and antimicrobial agents have also been developed based on QS regulation on bacterial infections. In addition, to meet the requirements for the detection/quantification of QS signaling molecules for research and application, different biosensors have been constructed, which will also be reviewed here. QS regulation is essential to bacterial survival and important to human health. A better understanding of QS could lead better control/manipulation of bacteria, thus making them more helpful to people.}, 
location = {Biofuels Institute, School of the Environment, Jiangsu University, 301 Xuefu Road,  212013, Zhenjiang, Jiangsu Province, China.}, }

@Article{Cornforth2014,
author = {Cornforth, DM and Popat, R and McNally, L and Gurney, J and Scott-Phillips, TC and Ivens, A and Diggle, SP and Brown, SP}, 
title = {Combinatorial quorum sensing allows bacteria to resolve their social and physical environment.}, 
journal = {Proc Natl Acad Sci U S A}, 
volume = {111}, 
number = {11}, 
pages = {4280--4284}, 
year = {2014}, 
abstract = {Quorum sensing (QS) is a cell-cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay between its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic  responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication.}, 
location = {Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.}, 
keywords = {logic, lasB},}

@Article{Rattray2022,
author = {Rattray, JB and Thomas, SA and Wang, Y and Molotkova, E and Gurney, J and Varga, JJ and Brown, SP}, 
title = {Bacterial Quorum Sensing Allows Graded and Bimodal Cellular Responses to Variations in Population Density.}, 
journal = {mBio}, 
volume = {13}, 
number = {3}, 
pages = {e0074522}, 
year = {2022}, 
abstract = {Quorum sensing (QS) is a mechanism of cell-cell communication that connects gene expression to environmental conditions (e.g., cell density) in many bacterial species, mediated by diffusible signal molecules. Current functional studies focus on qualitatively distinct QS ON/OFF states. In the context of density sensing, this view led to the adoption of a  analogy in which populations sense when they are above a sufficient density (i.e., ) to efficiently turn on cooperative behaviors. This framework overlooks the potential for intermediate, graded responses to shifts in the environment. In this study, we tracked QS-regulated protease (lasB) expression and showed that Pseudomonas aeruginosa can deliver a graded behavioral response to fine-scale variation in population density, on both the population and single-cell scales. On the population scale, we saw a graded response to variation in population density (controlled by culture carrying capacity). On the single-cell scale, we saw significant bimodality at higher densities, with separate OFF and ON subpopulations that responded differentially to changes in density: a static OFF population of cells and increasing intensity of expression among the ON population of cells. Together, these results indicate that QS can tune gene expression to graded environmental change, with no critical cell mass or  at which behavioral responses are activated on either the individual-cell or population scale. In an infection context, our results indicate there is not a hard threshold separating a quorate  mode from a subquorate  mode. IMPORTANCE Bacteria can be highly social, controlling collective behaviors via cell-cell communication mechanisms known as quorum sensing (QS). QS is now a large research field, yet a basic question remains unanswered: what is the environmental resolution of QS? The notion of a threshold, or  separating coordinated ON and OFF states is a central dogma in QS, but recent studies have shown heterogeneous responses at a single cell scale. Using Pseudomonas aeruginosa, we showed that populations generate graded responses to environmental variation through shifts in the proportion of cells responding and the intensity of responses. In an infection context, our results indicate that there is not a hard threshold separating a quorate  mode and a subquorate  mode.}, 
location = {School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Graduate Program in Quantitative Biosciences (QBioS), Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. The Institute for Data Engineering and Science (IDEaS), Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. School of Biological Sciences, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA. Center for Microbial Dynamics and Infection, Georgia Institute of Technologygrid.213917.f, Atlanta, Georgia, USA.}, }