Quorum sensing controls persistence, resuscitation, and virulence of Legionella subpopulations in biofilms.
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SUBMITTER: Personnic N
PROVIDER: S-EPMC7852695 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Clonal bacterial populations respond to unfavorable conditions with growth arrest and 20 persistence. Here we show that quorum sensing (QS) determines functionally distinct subpopulations of non-growing, virulent Legionella. QS increases the fraction of bacteria re- initiating growth in microcolonies, while it restricts the ratio of bacteria resuming growth in free- living protozoan predators. QS continues to govern the population heterogeneity throughout growth. Intracellular non-growers and growing bacteria are characterized by distinct proteomes 25 reflecting different stress and drug tolerance as well as alternative metabolic pathways. Strikingly, individual intracellular non-growers are persisters, which endure host killing mechanisms, produce virulence factors, form a replication-permissive compartment, and are highly infectious. Thus, QS underlies a bet-hedging strategy of non-growing intracellular bacterial pathogens to resume growth and to fine-tune virulence.
2019-11-19 | PXD015106 | Pride
Project description:The main objectives of this work were to investigate the effect of atmospheric cold plasma (ACP) against a range of microbial biofilms commonly implicated in foodborne and healthcare associated human infections and against P. aeruginosa quorum sensing (QS)-regulated virulence factors, such as pyocyanin, elastase (Las B) and biofilm formation capacity post-ACP treatment. The effect of processing factors, namely treatment time and mode of plasma exposure on antimicrobial activity of ACP were also examined. Antibiofilm activity was assessed for E. coli, L. monocytogenes and S. aureus in terms of reduction of culturability and retention of metabolic activity using colony count and XTT assays, respectively. All samples were treated 'inpack' using sealed polypropylene containers with a high voltage dielectric barrier discharge ACP generated at 80 kV for 0, 60, 120 and 300 s and a post treatment storage time of 24 h. According to colony counts, ACP treatment for 60 s reduced populations of E. coli to undetectable levels, whereas 300 s was necessary to significantly reduce populations of L. monocytogenes and S. aureus biofilms. The results obtained from XTT assay indicated possible induction of viable but non culturable state of bacteria. With respect to P. aeruginosa QS-related virulence factors, the production of pyocyanin was significantly inhibited after short treatment times, but reduction of elastase was notable only after 300 s and no reduction in actual biofilm formation was achieved post-ACP treatment. Importantly, reduction of virulence factors was associated with reduction of the cytotoxic effects of the bacterial supernatant on CHO-K1 cells, regardless of mode and duration of treatment. The results of this study point to ACP technology as an effective strategy for inactivation of established biofilms and may play an important role in attenuation of virulence of pathogenic bacteria. Further investigation is warranted to propose direct evidence for the inhibition of QS and mechanisms by which this may occur.
| S-EPMC4577073 | biostudies-literature
Project description:Several serious diseases are caused by biofilm-associated Staphylococcus aureus, infections in which the accessory gene regulator (agr) quorum-sensing system is thought to play an important role. We studied the contribution of agr to biofilm development, and we examined agr-dependent transcription in biofilms. Under some conditions, disruption of agr expression had no discernible influence on biofilm formation, while under others it either inhibited or enhanced biofilm formation. Under those conditions where agr expression enhanced biofilm formation, biofilms of an agr signaling mutant were particularly sensitive to rifampin but not to oxacillin. Time lapse confocal scanning laser microscopy showed that, similar to the expression of an agr-independent fluorescent reporter, biofilm expression of an agr-dependent reporter was in patches within cell clusters and oscillated with time. In some cases, loss of fluorescence appeared to coincide with detachment of cells from the biofilm. Our studies indicate that the role of agr expression in biofilm development and behavior depends on environmental conditions. We also suggest that detachment of cells expressing agr from biofilms may have important clinical implications.
| S-EPMC355980 | biostudies-literature
Project description:Pseudomonas aeruginosa uses quorum sensing to regulate the expression of virulence factors. In static environments, spatial structures, such as biofilms, can increase the expression of these virulence factors. However, in natural settings, biofilms are exposed to physical forces that disrupt spatial structure, which may affect the expression of virulence factors regulated by quorum sensing. We show that periodically disturbing biofilms composed of P. aeruginosa using a physical force reduces the expression of quorum sensing-regulated virulence factors. At an intermediate disturbance frequency, the expression of virulence factors in the las, rhl, and pqs regulons is reduced. Mathematical modeling suggests that perturbation of the pqsR receptor is critical for this reduction. Removing the lasR receptor enhances the reduction in the expression of virulence factors as a result of disturbance. Our results allow identification of environments where virulence is reduced and implicate the lasR receptor as having a buffering role against disturbance.
| S-EPMC10225924 | biostudies-literature
Project description:Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms AI production should be a protected function not directly tied to metabolism.
| S-EPMC8166027 | biostudies-literature
Project description:Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum-sensing systems that detect the density of other bacteria around them. A key example of such group behavior is biofilm formation, in which communities of cells attach to a surface and envelope themselves in secreted polymers. Curiously, after reaching high cell density, some bacterial species activate polymer secretion, whereas others terminate polymer secretion. Here, we investigate this striking variation in the first evolutionary model of quorum sensing in biofilms. We use detailed individual-based simulations to investigate evolutionary competitions between strains that differ in their polymer production and quorum-sensing phenotypes. The benefit of activating polymer secretion at high cell density is relatively straightforward: secretion starts upon biofilm formation, allowing strains to push their lineages into nutrient-rich areas and suffocate neighboring cells. But why use quorum sensing to terminate polymer secretion at high cell density? We find that deactivating polymer production in biofilms can yield an advantage by redirecting resources into growth, but that this advantage occurs only in a limited time window. We predict, therefore, that down-regulation of polymer secretion at high cell density will evolve when it can coincide with dispersal events, but it will be disfavored in long-lived (chronic) biofilms with sustained competition among strains. Our model suggests that the observed variation in quorum-sensing behavior can be linked to the differing requirements of bacteria in chronic versus acute biofilm infections. This is well illustrated by the case of Vibrio cholerae, which competes within biofilms by polymer secretion, terminates polymer secretion at high cell density, and induces an acute disease course that ends with mass dispersal from the host. More generally, this work shows that the balance of competition within and among biofilms can be pivotal in the evolution of quorum sensing.
| S-EPMC2214811 | biostudies-literature
Project description:Legionella pneumophila is a Gram-negative, environmental bacterium, which causes the life-threatening pneumonia Legionnaires’ disease. The facultative intracellular bacterium forms biofilms and employs the Icm/Dot type IV secretion system (T4SS) to replicate in amoebae and macrophages. The Legionella quorum sensing (Lqs) system and the transcription factor LvbR form a regulatory network controlling various traits, including bacterial motility, virulence and biofilm architecture. Here we show by comparative proteomics that in biofilms formed by L. pneumophila mutant strains lacking LvbR or the response regulator LqsR, proteins encoded by the 133 kb fitness island and components of the flagellum (FlaA) are downregulated. Confocal microscopy revealed that the ∆lqsR or ∆flaA mutant strains formed biofilms of the same patchy morphology as the parental strain JR32, while the ∆lvbR mutant forms a mat-like biofilm as previously shown. Acanthamoeba castellanii amoebae migrated more slowly through biofilms formed by the ∆lvbR, ∆lqsR or ∆flaA mutant strains, and amoebae migration was impaired in biofilms formed by L. pneumophila lacking a functional Icm/Dot T4SS (∆icmT) or the secreted effector proteins LegG1 and PpgA. Amoebae migrating through biofilms formed by JR32, ∆lvbR or ∆icmT were decorated by clusters of bacteria, while amoebae in ∆lqsR or ∆flaA biofilms were not. Taken together, the Lqs system, LvbR, FlaA and the Icm/Dot T4SS regulate migration of A. castellanii through L. pneumophila biofilms, and – with the exception of the T4SS – also regulate bacterial cluster formation on the amoeba. Hence, amoebae migration through L. pneumophila biofilms is regulated by bacterial quorum sensing, virulence and motility.
2022-06-08 | PXD030337 | Pride
Project description:Cell-cell communication, also termed quorum sensing (QS), is a widespread process that coordinates gene expression in bacterial populations. The generally accepted view is that QS optimizes the cell density-dependent benefit attained from cooperative behaviors, often in the form of secreted products referred to as "public goods." This view is challenged by an increasing number of cell-associated products or "private goods" reported to be under QS-control for which a collective benefit is not apparent. A prominent example is nucleoside hydrolase from Pseudomonas aeruginosa, a periplasmic enzyme that catabolizes adenosine. Several recent studies have shown that private goods can function to stabilize cooperation by co-regulated public goods, seemingly explaining their control by QS. Here we argue that this property is a by-product of selection for other benefits rather than an adaptation. Emphasizing ecophysiological context, we propose alternative explanations for the QS control of private goods. We suggest that the benefit attained from private goods is associated with high cell density, either because a relevant ecological condition correlates with density, or because the private good is, directly or indirectly, involved in cooperative behavior. Our analysis helps guide a systems approach to QS, with implications for antivirulence drug design and synthetic biology.
| S-EPMC5437708 | biostudies-literature
Project description:Legionella spp. are ubiquitous bacteria principally found in water networks and ∼20 species are implicated in Legionnaire's disease. Among them, Legionella pneumophila is an intracellular pathogen of environmental protozoa, responsible for ∼90% of cases in the world. Legionella pneumophila regulates in part its virulence by a quorum sensing system named "Legionella quorum sensing," composed of a signal synthase LqsA, two histidine kinase membrane receptors LqsS and LqsT and a cytoplasmic receptor LqsR. To date, this communication system was only found in L. pneumophila. Here, we investigated 58 Legionella genomes to determine the presence of a lqs cluster or homologous receptors using TBlastN. This analysis revealed three categories of species: 19 harbored a complete lqs cluster, 20 did not possess lqsA but maintained the receptor lqsR and/or lqsS, and 19 did not have any of the lqs genes. No correlation was observed between pathogenicity and the presence of a quorum sensing system. We determined by RT-qPCR that the lqsA gene was expressed at least in four strains among different species available in our laboratory. Furthermore, we showed that the lqs genomic region was conserved even in species possessing only the receptors of the quorum sensing system, indicating an ancestral acquisition and various loss dynamics during evolution. This system could therefore function in interspecific communication as well.
| S-EPMC8023197 | biostudies-literature
Project description:This manuscript describes the fabrication of arrays of spatially confined chambers embossed in a layer of poly(ethylene glycol) diacrylate (PEGDA) and their application to studying quorum sensing between communities of Pseudomonas aeruginosa. We hypothesized that biofilms may produce stable chemical signaling gradients in close proximity to surfaces, which influence the growth and development of nearby microcolonies into biofilms. To test this hypothesis, we embossed a layer of PEGDA with 1.5-mm wide chambers in which P. aeruginosa biofilms grew, secreted homoserine lactones (HSLs, small molecule regulators of quorum sensing), and formed spatial and temporal gradients of these compounds. In static growth conditions (i.e., no flow), nascent biofilms secreted N-(3-oxododecanoyl) HSL that formed a gradient in the hydrogel and was detected by P. aeruginosa cells that were ?8 mm away. Diffusing HSLs increased the growth rate of cells in communities that were <3 mm away from the biofilm, where the concentration of HSL was >1 ?M, and had little effect on communities farther away. The HSL gradient had no observable influence on biofilm structure. Surprisingly, 0.1-10 ?M of N-(3-oxododecanoyl) HSL had no effect on cell growth in liquid culture. The results suggest that the secretion of HSLs from a biofilm enhances the growth of neighboring cells in contact with surfaces into communities and may influence their composition, organization, and diversity.
| S-EPMC3076519 | biostudies-literature