Explore the vast range of titles available.

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 “quorum,” separating coordinated ON and OFF states is a central dogma in QS, but recent studies have shown heterogeneous responses at a single cell scale. 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 “quorum” analogy in which populations sense when they are above a sufficient density (i.e., “quorate”) 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 “quorum” 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 “attack” mode from a subquorate “stealth” 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 “quorum,” 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 “attack” mode and a subquorate “stealth” mode.

Bacteriocins are gene-encoded antimicrobial peptides produced by bacteria. These peptides are heterogeneous in terms of structure, antimicrobial activities, biosynthetic clusters, and regulatory mechanisms. Bacteriocins are widespread in nature and may contribute to microbial diversity due to their capacity to target specific bacteria. Primarily studied as food preservatives and therapeutic agents, their function in natural settings is however less known. This review emphasizes the ecological significance of bacteriocins as multifunctional peptides by exploring bacteriocin distribution, mobility, and their impact on bacterial population dynamics and biofilms.

Bacteria coordinate gene expression in a cell density-dependent manner in a communication process called quorum sensing (QS). The expression of virulence factors, biofilm formation and enzyme production are QS-regulated phenotypes that can interfere in human health. Due to this importance, there is great interest in inhibiting QS, comprising an anti-virulence strategy. This work aimed to evaluate the effect of selected phenolic compounds on the inhibition of QS-regulated phenotypes in Pseudomonas aeruginosa PAO1, using concentrations that do not interfere in bacterial growth. This is one of the main premises for studying the effect of compounds on QS. Firstly, an in-silico study with the LasR and RhlR proteins of P. aeruginosa by molecular docking of 82 phenolic compounds was performed. Then, a screening with 13 selected phenolic compounds was performed, using biosensor strains P. aeruginosa lasB-gfp and P. aeruginosa rhlA-gfp , which emit fluorescence when the QS system is activated. From this assay, eight compounds were selected and evaluated for inhibition of pyocyanin, rhamnolipids, proteases, elastase, and motility. The compounds variably inhibited the evaluated virulence factors. The greatest inhibitions were observed for swarming motility, achieving inhibition rates of up to 50% for baicalein (500 µM) and curcumin (50 µM). Notably, curcumin showed satisfactory inhibition for all phenotypes even at lower concentrations (12.5 to 50 µM) compared to the other compounds (125 to 500 µM). Four compounds - rosmarinic acid, baicalein, curcumin, and resveratrol - were finally tested against biofilm formation observed by optical microscopy. This study demonstrated that phenolic compounds exhibit strong in silico binding to P. aeruginosa LasR and RhlR proteins and variably inhibit QS-regulated phenotypes in vitro. Although no biofilm inhibition was observed, future studies combining compounds and exploring molecular mechanisms are recommended. These findings highlight the biotechnological potential of phenolic compounds for future applications in the food, clinical, and pharmaceutical fields.

Specific recognition of cognate signals is considered fundamental to cell signaling circuits as it creates fidelity in the communication system. In bacterial quorum sensing (QS), receptor specificity ensures that bacteria cooperate only with kin. There are examples, however, of QS receptors that respond promiscuously to multiple signals. “Eavesdropping” by these promiscuous receptors can be beneficial in both interspecies competition and cooperation. Despite their potential significance, we know little about the prevalence of promiscuous QS receptors. Further, many studies rely on methods requiring receptor overexpression, which is known to increase apparent promiscuity. By systematically studying QS receptors in their natural parent strains, we find that the receptors display a wide range of selectivity and that there is potential for significant cross talk between QS systems. Our results provide a basis for hypotheses about the evolution and function of promiscuous signal receptors and for predictions about interspecies interactions in complex microbial communities. Many species of proteobacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). Most AHL receptors are thought to be specific for their cognate signal, ensuring that bacteria cooperate and share resources only with closely related kin cells. Although specificity is considered fundamental to QS, there are reports of “promiscuous” receptors that respond broadly to nonself signals. These promiscuous responses expand the function of QS systems to include interspecies interactions and have been implicated in both interspecies competition and cooperation. Because bacteria are frequently members of polymicrobial communities, AHL cross talk between species could have profound impacts. To better understand the prevalence of QS promiscuity, we measured the activity of seven QS receptors in their native host organisms. To facilitate comparison of our results to previous studies, we also measured receptor activity using heterologous expression in Escherichia coli . We found that the standard E. coli methods consistently overestimate receptor promiscuity and sensitivity and that overexpression of the receptors is sufficient to account for the discrepancy between native and E. coli reporters. Additionally, receptor overexpression resulted in AHL-independent activity in Pseudomonas aeruginosa . Using our activation data, we developed a quantitative score of receptor selectivity. We find that the receptors display a wide range of selectivity and that most receptors respond sensitively and strongly to at least one nonself signal, suggesting a broad potential for cross talk between QS systems. IMPORTANCE Specific recognition of cognate signals is considered fundamental to cell signaling circuits as it creates fidelity in the communication system. In bacterial quorum sensing (QS), receptor specificity ensures that bacteria cooperate only with kin. There are examples, however, of QS receptors that respond promiscuously to multiple signals. “Eavesdropping” by these promiscuous receptors can be beneficial in both interspecies competition and cooperation. Despite their potential significance, we know little about the prevalence of promiscuous QS receptors. Further, many studies rely on methods requiring receptor overexpression, which is known to increase apparent promiscuity. By systematically studying QS receptors in their natural parent strains, we find that the receptors display a wide range of selectivity and that there is potential for significant cross talk between QS systems. Our results provide a basis for hypotheses about the evolution and function of promiscuous signal receptors and for predictions about interspecies interactions in complex microbial communities.

Significance Cooperation is subject to social cheating. Cheats benefit from the activity of cooperators and gain a fitness advantage. One way higher organisms prevent infiltration by cheats is policing: Cooperators penalize cheats at some cost to themselves. Cooperating groups of bacteria are susceptible to social cheating, but little is known about bacterial policing. We have built on an understanding a quorum-sensing regulated cooperative activity in Pseudomonas aeruginosa to show that quorum sensing control of and resistance to cyanide production serves as a cheater policing mechanism. Understanding how bacteria cooperate and how they control social cheats has evolutionary implications, provides important insights about ways to control bacterial populations, and has ramifications with respect to synthetic system design. The bacterium Pseudomonas aeruginosa is an opportunistic human pathogen that uses a quorum sensing signal cascade to activate expression of dozens of genes when sufficient population densities have been reached. Quorum sensing controls production of several key virulence factors, including secreted proteases such as elastase. Cooperating groups of bacteria growing on protein are susceptible to social cheating by quorum-sensing defective mutants. A possible way to restrict cheater emergence is by policing where cooperators produce costly goods to sanction or punish cheats. The P. aeruginosa LasR-LasI quorum sensing system controls genes including those encoding proteases and also those encoding a second quorum-sensing system, the RhlR-RhlI system, which controls numerous genes including those for cyanide production. By using RhlR quorum sensing mutants and cyanide synthesis mutants, we show that cyanide production is costly and cyanide-producing cooperators use cyanide to punish LasR-null social cheaters. Cooperators are less susceptible to cyanide than are LasR mutants. These experiments demonstrate policing in P. aeruginosa , provide a mechanistic understanding of policing, and show policing involves the cascade organization of the two quorum sensing systems in this bacterium.

The study of quorum sensing (QS) has gained critical importance, offering insights into bacterial and microorganism communication. QS, regulated by autoinducers, synchronizes collective bacterial behaviors across diverse chemical signals and target genes. This review highlights innovative approaches to regulating QS, emphasizing the potential of quorum quenching and QS inhibitors to mitigate bacterial pathogenicity. These strategies have shown promise in aquaculture and plant resistance, disrupting QS pathways to combat infections. QS also provides opportunities for developing biosensors for early disease detection and preventing biofilm formation, which is critical to overcoming antimicrobial resistance. The applications of QS extend to cancer therapy, with targeted drug delivery systems utilizing QS mechanisms. Advancements in QS regulation, such as the use of nanomaterials, hydrogels, and microplastics, provide novel methods to modulate QS systems. This review explores the latest developments in QS, recognizing its significance in controlling bacterial behavior and its broad impacts on human health and disease management. Integrating these insights into therapeutic strategies and diagnostics represents a pivotal opportunity for medical progress. Quorum quenching and quorum sensing inhibitors show significant potential in regulating bacterial quorum sensing systems and have been widely applied across various fields, including cancer treatment, antimicrobial resistance, marine management, microplastic reduction, hydrogel technology, and nanomaterials development.

Intercellular communication is a widespread phenomenon in all domains of life. Bacteria have developed many ways of communicating with one another and with other species, either prokaryotic or eukaryotic. RNA has been a key molecule since the beginning of life on Earth, and is one of the carriers of information. Given the current antibiotic crisis, understanding the way in which pathogens communicate can lead towards improved ways to control infections when antimicrobial therapy is not possible. Different subspecies of RNA, non-coding, and of small size, designated here as ncRNAs, have been in recent years the subject of a great research effort, and results have contributed to a growing field of knowledge. This review focuses on four different aspects of ncRNA involvement in cell-to-cell communications during bacterial infections: pathogen recognition by the host, alteration of host microRNA profiles, production of domestic and secreted forms of ncRNAs and subversion of the host responses. The current review article focuses on the most recent discoveries in the field and gives an integrative idea based on the discussed studies.

The possible carrier role of Outer Membrane Vesicles (OMVs) for small regulatory noncoding RNAs (sRNAs) has recently been demonstrated. Nevertheless, to perform their function, these sRNAs usually need a protein cofactor called Hfq. In this work we show, by using a combination of infrared and circular dichroism spectroscopies, that Hfq, after interacting with the inner membrane, can be translocated into the periplasm, and then be exported in OMVs, with the possibility to be bound to sRNAs. Moreover, we provide evidence that Hfq interacts with and is inserted into OMV membranes, suggesting a role for this protein in the release of sRNA outside the vesicle. These findings provide clues to the mechanism of host–bacteria interactions which may not be defined solely by protein–protein and protein–outer membrane contacts, but also by the exchange of RNAs, and in particular sRNAs.

The evolutionary dynamics of cell-to-cell communication in bacterial populations can be examined using mathematical modeling and computer simulations. In the present study, the model of bacterial quorum sensing in colonies cultivated on nutrient media is explored from theoretical and computational points of view. The proposed approach is based on combining the deterministic model for bacterial nutrient-dependent biomass growth and the reaction-diffusion model describing spatial-temporal characteristics of bacterial quorum sensing. The unique solvability of the initial-boundary value problem for the mathematical model of bacterial quorum sensing is proved. The existence of a stationary state is proven and the conditions for its stability are presented. The theoretical results are based on the derivation of new a priori estimates for the solution of the system of semilinear parabolic and elliptic equations. The nonlinear differential problem is solved numerically and the software implementation is executed in combination with the procedure of fractal dimension measure for bacterial pattern boundaries. A series of computational experiments is conducted to analyze the behavior of key chemical substances associated with quorum sensing attributed to Pseudomonas bacteria during the formation of dendrites as well as floral patterns in nutrient media.

To understand how bacterial populations function and evolve, it is essential to identify socially significant subpopulations, including previously unrecognized types of cheaters. In this study, we uncover an unexpected role of RNA polymerase (RNAP) in regulating quorum sensing (QS) and QS-associated social behaviors in P. aeruginosa . Specifically, we demonstrate that the α subunit of RNAP (RpoA) is a key regulatory component in this process. A single-nucleotide mutation within the C-terminal domain of RpoA was found to alter QS activity, driving an environment-dependent transition between cooperative and cheating phenotypes. This discovery of this novel, noncanonical QS cheater mutant offers new insights into intra-population interactions, population stability, and evolutionary dynamics. These findings carry significant implications for microbial ecology and deepen our understanding of social evolution in bacterial communities.