Quorum sensing regulation in bacteria of the family enterobacteriaceae

Bacteria are able to sense an increase in population density and can respond to it by coordinated regulation of the expression of certain sets of genes in the total population of bacteria. This specific mode of regulation is known as Quorum Sensing (QS). The QS systems include low-molecular-weight signaling molecules of different chemical nature and the regulatory proteins that interact with the signaling molecules. The QS systems are global regulators of bacterial gene expression. They play an important role in controlling metabolic processes in bacteria. This review describes QS systems in members of the bacterial family Enterobacteriaceae functioning with the involvement of various signaling molecules, including N-acyl-homoserine lactones, AI-2, AI-3, peptides, and indole. The differences of the QS system in these bacteria from those in other taxonomic groups of bacteria are discussed. Data on the role of different types of QS systems in the regulation of different cellular processes in bacteria, i.e., their virulence, the synthesis of enzymes and antibiotics, biofilm formation, apoptosis, etc. are presented.     

Quorum-sensing regulation of gene expression: Fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.     

Quorum-sensing regulation of gene expression: fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.     

Presence of Quorum-Sensing-Mediated Gene Regulation in Pathogenic Ice-Nucleation-Active (INA) Bacteria

Nine out of a total of 20 pathogenic ice-nucleation-active bacteria, with different levels of inducible INA, were tested and found positive for their ability to synthesize quorum-sensing (QS) signals. The bacteria were isolated from willow plants and belonged to the genera Bacillus, Erwinia, Pseudomonas and Sphingomonas. As reporter bacteria, to detect the homoserine lactone (HSL) autoinducer, Agrobacterium tumefaciens, Chromobacterium violaceum, Pseudomonas aeroginosa, Aeromonas hydrophila and Vibrio fischeri strains were used. We thus provide evidence that pathogenic ice-nucleation bacteria with inducible INA produce QS signals that in other bacteria have been shown to be in the control of genes of importance for pathogenicity.     

Distinctive features of the Gac-Rsm pathway in plant-associated Pseudomonas

Productive plant–bacteria interactions, either beneficial or pathogenic, require that bacteria successfully sense, integrate and respond to continuously changing environmental and plant stimuli. They use complex signal transduction systems that control a vast array of genes and functions. The Gac-Rsm global regulatory pathway plays a key role in controlling fundamental aspects of the apparently different lifestyles of plant beneficial and phytopathogenic Pseudomonas as it coordinates adaptation and survival while either promoting plant health (biocontrol strains) or causing disease (pathogenic strains). Plant-interacting Pseudomonas stand out for possessing multiple Rsm proteins and Rsm RNAs, but the physiological significance of this redundancy is not yet clear. Strikingly, the components of the Gac-Rsm pathway and the controlled genes/pathways are similar, but the outcome of its regulation may be opposite. Therefore, identifying the target mRNAs bound by the Rsm proteins and their mode of action (repression or activation) is essential to explain the resulting phenotype. Some technical considerations to approach the study of this system are also given. Overall, several important features of the Gac-Rsm cascade are now understood in molecular detail, particularly in Pseudomonas protegens CHA0, but further questions remain to be solved in other plant-interacting Pseudomonas.     

The substrate-dependent regulatory effects of the AfeI/R system in Acidithiobacillus ferrooxidans reveals the novel regulation strategy of quorum sensing in acidophiles

A LuxI/R-like quorum sensing (QS) system (AfeI/R) has been reported in the acidophilic and chemoautotrophic Acidithiobacillus spp. However, the function of AfeI/R remains unclear because of the difficulties in the genetic manipulation of these bacteria. Here, we constructed different afeI mutants of the sulfur- and iron-oxidizer A. ferrooxidans, identified the N-acyl homoserine lactones (acyl-HSLs) synthesized by AfeI, and determined the regulatory effects of AfeI/R on genes expression, extracellular polymeric substance synthesis, energy metabolism, cell growth and population density of A. ferrooxidans in different energy substrates. Acyl-HSLs-mediated distinct regulation strategies were employed to influence bacterial metabolism and cell growth of A. ferrooxidans cultivated in either sulfur or ferrous iron. Based on these findings, an energy-substrate-dependent regulation mode of AfeI/R in A. ferrooxidans was illuminated that AfeI/R could produce different types of acyl-HSLs and employ specific acyl-HSLs to regulate specific genes in response to different energy substrates. The discovery of the AfeI/R-mediated substrate-dependent regulatory mode expands our knowledge on the function of QS system in the chemoautotrophic sulfur- and ferrous iron-oxidizing bacteria, and provides new insights in understanding energy metabolism modulation, population control, bacteria-driven bioleaching process, and the coevolution between the acidophiles and their acidic habitats.     

Multiplicity of Quorum Quenching Enzymes: A Potential Mechanism to Limit Quorum Sensing Bacterial Population

Bacteria express certain of their characteristics especially, pathogenicity factors at high cell densities. The process is termed as quorum sensing (QS). QS operates via signal molecules such as acylhomoserine lactones (AHLs). Other bacteria inhibit QS through the inactivation of AHL signals by producing enzymes like AHL-lactonases and -acylases. Comparative genomic analysis has revealed the multiplicity of genes for AHL lactonases (up to 12 copies per genome) among Bacillus spp. and that of AHL-acylases (up to 5 copies per genome) among Pseudomonas spp. This genetic evolution can be envisaged to enable host to withstand the attacks from bacterial population, which regulates its functioning through QS.     

Bacterial cell‐to‐cell signaling promotes the evolution of resistance to parasitic bacteriophages

The evolution of host–parasite interactions could be affected by intraspecies variation between different host and parasite genotypes. Here we studied how bacterial host cell‐to‐cell signaling affects the interaction with parasites using two bacteria‐specific viruses (bacteriophages) and the host bacterium Pseudomonas aeruginosa that communicates by secreting and responding to quorum sensing (QS) signal molecules. We found that a QS‐signaling proficient strain was able to evolve higher levels of resistance to phages during a short‐term selection experiment. This was unlikely driven by demographic effects (mutation supply and encounter rates), as nonsignaling strains reached higher population densities in the absence of phages in our selective environment. Instead, the evolved nonsignaling strains suffered relatively higher growth reduction in the absence of the phage, which could have constrained the phage resistance evolution. Complementation experiments with synthetic signal molecules showed that the Pseudomonas quinolone signal (PQS) improved the growth of nonsignaling bacteria in the presence of a phage, while the activation of las and rhl quorum sensing systems had no effect. Together, these results suggest that QS‐signaling can promote the evolution of phage resistance and that the loss of QS‐signaling could be costly in the presence of phages. Phage–bacteria interactions could therefore indirectly shape the evolution of intraspecies social interactions and PQS‐mediated virulence in P. aeruginosa.     

Quorum sensing of genes expression--perspective drug target against bacterial pathogenicity

Bacteria are capable to sense an increase of cell density population and to reply quickly and coordinately by the induction of special sets of genes. This type of the regulation was named Quorum Sensing (QS); it is based on the effect of low-molecular-weight signaling molecules of different nature (autoinducers) which accumulate in the culture at high density of bacterial population and interact with receptor regulatory proteins. QS systems are the global regulators of bacterial genes expression and play a key role in the control of many metabolic processes in cell including the regulation of virulence of bacteria. Here we review the molecular mechanisms of QS systems functioning in bacteria belonging to different taxonomic groups and discuss the potential of QS regulation as a new drug target for the treatment of bacterial infections. At present this approach is accounted as a new alternative strategy of antimicrobial therapy directed on the development of drugs inhibiting QS regulation and active just against pathogenicity of bacteria (antipathogenic drugs). Such a strategy allows to avoid a wide dissemination of resistant forms of pathogenic bacteria and the formation of biofilms increasing in many times the resistance of bacteria to drug preparations.     

Growth phase-differential quorum sensing regulation of anthranilate metabolism in <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

Pseudomonas quinolone signal (PQS) plays a role in the regulation of virulence genes and it is intertwined in the las/rhl quorum sensing (QS) circuits of Pseudomonas aeruginosa. PQS is synthesized from anthranilate by pqsA-D and pqsH whose expression is influenced by the las/rhl systems. Since anthranilate can be degraded by functions of antABC and catBCA, PQS synthesis might be regulated by the balance between the expression of the pqsA-D/phnAB, pqsH, antABC, and catBCA gene loci. antA and catA are repressed by LasR during log phase and activated by RhlR in late stationary phase, whereas pqsA-E/phnAB is activated by LasR in log phase and repressed by RhlR. QscR represses both but each repression occurs in a different growth phase. This growth phase-differential regulation appears to be accomplished by the antagonistic interplay of LasR, RhlR, and QscR, mediated by two intermediate regulators, AntR and PqsR, and their cofactors, anthranilate and PQS, where the expressions of antR and pqsR and the production of anthranilate and PQS are growth phase-differentially regulated by QS systems. Especially, the anthranilate level increases in an RhlR-dependent manner at late stationary phase. From these results, we suggest that RhlR and LasR regulate the anthranilate metabolism in a mutually antagonistic and growth phase-differential manner by affecting both the expressions and activities of AntR and PqsR, and that QscR also phase-differentially represses both LasR and RhlR functions in this regulation.     

Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence

Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.     

Quorum sensing disruption regulates hydrolytic enzyme and biofilm production in estuarine bacteria

Biofilms of heterotrophic bacteria cover organic matter aggregates and constitute hotspots of mineralization, primarily acting through extracellular hydrolytic enzyme production. Nevertheless, regulation of both biofilm and hydrolytic enzyme synthesis remains poorly investigated, especially in estuarine ecosystems. In this study, various bioassays, mass spectrometry and genomics approaches were combined to test the possible involvement of quorum sensing (QS) in these mechanisms. QS is a bacterial cell–cell communication system that relies notably on the emission of N-acylhomoserine lactones (AHLs). In our estuarine bacterial collection, we found that 28 strains (9%), mainly Vibrio, Pseudomonas and Acinetobacter isolates, produced at least 14 different types of AHLs encoded by various luxI genes. We then inhibited the AHL QS circuits of those 28 strains using a broad-spectrum lactonase preparation and tested whether biofilm production as well as β-glucosidase and leucine-aminopeptidase activities were impacted. Interestingly, we recorded contrasted responses, as biofilm production, dissolved and cell-bound β-glucosidase and leucine-aminopeptidase activities significantly increased in 4%–68% of strains but decreased in 0%–21% of strains. These findings highlight the key role of AHL-based QS in estuarine bacterial physiology and ultimately on biogeochemical cycles. They also point out the complexity of QS regulations within natural microbial assemblages.     

Interplay of two quorum sensing regulation systems of Vibrio fischeri

Many bacteria developed a possibility to recognise aspects of their environment or to communicate with each other by chemical signals. An important strategy is the so-called quorum sensing (QS), a regulatory mechanism for the gene expression, where the bacteria measure their own cell density by means of this signalling pathway. One of the best-studied species using QS is the marine luminescent bacterium Vibrio fischeri which is considered here as a model organism.The two main regulatory pathways (lux and ain) are combined to a regulation system, the dynamics is modelled by an ODE system. This system is analysed thoroughly, considering stationary states, dynamical behaviour and the possible biological meaning of it. The influence of different parameter values on the behaviour is examined, the same basic system is able to reflect the peculiarities of different bacteria strains (respectively, their mutants).     

Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa

The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (M vfR-mediated P QS and a nthranilate r egulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa. The deletion of mpaR increased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels of antABC encoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected by mpaR deletion. Data showed that MpaR directly activates the expression of mvfR, a master regulator of pqs system, and subsequently promotes PQS production. Accordingly, deletion of mpaR activates the expression of antABC genes, and thus, increases catechol production. We also demonstrated that MpaR represses the rhl quorum-sensing (QS) system, which has been shown to control antABC activity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation of mpaR promotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator of pqs system, which coordinately controls anthranilate metabolism and bacterial virulence in P. aeruginosa.     

Quorum sensing and communication in bacteria

Bacteria are able “to sense” an increase in the cell population density and to respond to it by the induction of special sets of genes. This type of regulation, called Quorum Sensing (QS), includes the production and excretion of low-molecular-weight signaling molecules (autoinducers, AI), which diffuse readily through the cell wall, from cells into the medium. As the bacterial population reaches the critical level of density, the concentration of these signaling molecules in the medium increases as a function of population density. On reaching the critical threshold concentration, AIs bind to specific receptor regulatory proteins, which induce the expression of target genes. By means of AIs, bacteria accomplish the communication that is the transmission of information between bacteria belonging to the same or different species, genera, and even families: the signaling molecules of some bacteria affect the receptors of others causing a coordinated reply of cells of the bacterial population. Bacteria of different taxonomic groups use the QS systems in regulation of a broad range of physiological activities. These processes include virulence, symbiosis, conjugation, biofilm formation, bioluminescence, synthesis of enzymes, antibiotic substances, etc. Here we review different QS systems of bacteria, the role of QS in bacterial communication, and some applied aspects of QS regulation application.     

Quorum Sensing Circuits in the Communicating Mechanisms of Bacteria and Its Implication in the Biosynthesis of Bacteriocins by Lactic Acid Bacteria: a Review

It is well established that bacteria communicate between each other by using different mechanisms; among which, quorum sensing (QS) is the best known one. Indeed, intra- and intercellular communications of microorganisms, as well as the regulation of metabolism and reaction to the surrounding environmental conditions, are carried out by using different signaling molecules. N-Acyl homoserine lactones control the QS in Gram-negative bacteria, while Gram-positive bacteria use communicating peptides. These compounds, by diffusing through the bacterial membrane cell from the extracellular medium, directly or indirectly control the expression of specific genes that induce bacteria to react to their surrounding environment and stressing agents. In the case of lactic acid bacteria and bifidobacteria which are widely used in the dairy industry, QS is of extreme importance for their survival and the extent of their activity in the dairy matrix. Moreover, it is also via QS that these bacteria synthesize various antimicrobial agents such as bacteriocins. The aim of this review is to highlight the quorum sensing circuits involved in the communicating mechanisms of bacteria with emphasis on current applications of QS in lactic acid bacteria. More particularly, the implication of QS in the biosynthesis of bacteriocins by lactic acid bacteria will be detailed.