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Quorum sensing

Quorum sensing is a form of cell-to-cell communication in bacteria that enables populations to collectively regulate gene expression in response to changes in cell density through the production and detection of diffusible signaling molecules known as autoinducers.^[1] This process allows individual bacteria to sense when their population has reached a critical threshold, often referred to as a "quorum," triggering synchronized behaviors that would be inefficient or impossible for solitary cells. First observed in the 1970s during studies of bioluminescence in the marine bacterium Aliivibrio fischeri, where light production was found to be density-dependent due to an autoinduction mechanism, quorum sensing was later formalized as a distinct phenomenon.^[1]^[2] The term "quorum sensing" was coined in 1994 by researchers Chris Fuqua, Stephen C. Winans, and Everett P. Greenberg to describe this density-responsive regulation mediated by the LuxR-LuxI family of proteins in Gram-negative bacteria. In Gram-negative species, autoinducers are typically acyl-homoserine lactones (AHLs) synthesized by enzymes like LuxI and detected by receptor proteins such as LuxR, which, upon binding, activate transcription of target genes.^[3] Gram-positive bacteria, in contrast, often employ peptide-based autoinducers that are exported and sensed via two-component systems involving histidine kinases and response regulators.^[1] These signaling pathways form positive feedback loops, amplifying the response as autoinducer concentrations rise with population growth.^[4] Quorum sensing coordinates a wide array of communal activities essential for bacterial survival and adaptation, including bioluminescence, sporulation, biofilm formation, antibiotic production, and virulence factor expression.^[1] For instance, in the pathogen Pseudomonas aeruginosa, multiple quorum sensing systems (such as Las and Rhl) regulate over 300 genes involved in biofilm development and toxin secretion, contributing to chronic infections in cystic fibrosis patients.^[5] Similarly, Vibrio cholerae uses quorum sensing to control cholera toxin production and biofilm formation, exacerbating disease transmission.^[4] In Staphylococcus aureus, the accessory gene regulator (Agr) system modulates virulence factors like toxins and adhesins, influencing skin and bloodstream infections.^[6] Beyond intraspecies communication, quorum sensing facilitates interspecies and even interkingdom interactions, such as influencing host immune responses or plant-microbe symbioses.^[7] The significance of quorum sensing extends to medical and environmental applications, as disrupting these pathways—through quorum quenching strategies like enzyme degradation of autoinducers—offers promising avenues for combating antibiotic-resistant biofilms and virulence without promoting resistance.^[1] Ongoing research highlights its evolutionary conservation across diverse bacterial phyla, underscoring quorum sensing as a fundamental mechanism in microbial ecology and pathogenesis.^[8]

History and Fundamentals

Discovery and Early Research

The phenomenon of quorum sensing was first uncovered through studies on bacterial bioluminescence in the early 1970s. Researchers Kenneth H. Nealson, Terry Platt, and J. Woodland Hastings investigated the marine bacterium Vibrio fischeri (now classified as Aliivibrio fischeri) and observed that light production occurred predominantly at high cell densities in liquid cultures, while dilute suspensions remained dark despite viable cells.^[9] This density-dependent expression suggested a regulatory mechanism linking luminescence to population size, as transferring cells from low- to high-density conditions rapidly induced glowing, whereas the reverse suppressed it.^[9] Key experiments revealed the involvement of a diffusible factor. Nealson and colleagues extracted a heat-stable, low-molecular-weight substance from high-density V. fischeri cultures, which, when added to low-density cells, triggered bioluminescence prematurely, indicating self-stimulation or autoinduction.^[10] In 1977, Nealson further characterized this process, demonstrating that autoinduction conserved energy by limiting luciferase synthesis to conditions where the metabolic cost of light emission was ecologically justified, such as in symbiotic associations with host organisms.^[10] These findings were synthesized in a comprehensive 1979 review by Nealson and Hastings, which emphasized the ecological significance of density-responsive control in bioluminescent bacteria and proposed autoinduction as a general adaptive strategy.^[11] Building on this foundation, research in the early 1990s expanded the scope beyond V. fischeri. Bonnie L. Bassler and collaborators examined Vibrio harveyi, identifying two parallel sensory pathways that regulated bioluminescence through distinct autoinducers, revealing a more complex system of intercellular signaling.^[12] This work established autoinduction as a conserved mechanism across Vibrio species. In 1994, Fuqua, Winans, and Greenberg coined the term "quorum sensing" in a seminal review, framing it as a widespread bacterial strategy for density-dependent gene regulation via LuxR-LuxI homologs, which broadened recognition of its implications for diverse physiological processes.^[13] By the early 2000s, similar systems were identified in other bacteria, solidifying quorum sensing as a fundamental mode of microbial communication.^[14]

Etymology and Terminology

The term "quorum sensing" was coined in 1994 by Clay Fuqua, Stephen C. Winans, and E. Peter Greenberg in a review article that synthesized early observations of density-dependent bacterial signaling.^[13] The name derives from "quorum," a legal and parliamentary term originating from the Latin quorum (genitive plural of qui, meaning "of whom"), referring to the minimum number of assembly members required to validate proceedings and make decisions.^[15] This analogy highlights how bacteria achieve a critical population threshold before collectively activating gene expression, much like a group reaching consensus for action.^[15] Quorum sensing is defined as a cell-to-cell communication mechanism in which bacteria produce, secrete, and detect extracellular signaling molecules called autoinducers to monitor local population density and synchronize behaviors through coordinated gene regulation.^[16] Autoinducers are diffusible compounds, often small and species-specific, that accumulate proportionally with cell numbers and trigger responses only when concentrations exceed a threshold, thereby linking individual actions to group-level outcomes.^[17] Key related terminology includes the Lux system, the first identified quorum sensing circuit from the marine bacterium Vibrio fischeri, where the luxI gene encodes an autoinducer synthase producing N-acyl homoserine lactones (AHLs), and luxR encodes a receptor that, upon binding the autoinducer, activates bioluminescence genes at high densities.^[13] Quorum quenching describes processes that disrupt this communication, such as enzymatic degradation of autoinducers or inhibition of receptors, preventing density-dependent gene activation.^[18] The terminology evolved from earlier concepts of "autoinduction," introduced in the 1970s to describe self-generated signals inducing light production in V. fischeri cultures, as observed by Nealson, Platt, and Hastings.^[19] By the 1990s, "quorum sensing" supplanted "autoinduction" to encompass broader density-responsive phenomena across bacterial species, emphasizing intercellular coordination over mere self-stimulation.^[19]

Core Mechanisms

General Principles

Quorum sensing is a form of cell-to-cell communication in bacteria that enables populations to sense their local density and coordinate gene expression accordingly. In this process, individual cells constitutively produce and release small signaling molecules into the surrounding environment at basal levels. As bacterial density rises, these molecules accumulate extracellularly rather than dissipating rapidly. When the local concentration surpasses a specific threshold, it binds to cognate receptors within the cells, initiating a cascade that alters the transcription of numerous genes to synchronize collective behaviors.^[1] The core components of quorum sensing include the synthesis and export of signaling molecules, their diffusion through the medium, recognition by dedicated receptors, and the resulting activation of transcriptional regulators. Signal production is typically constitutive but can become amplified through positive feedback once detection occurs. Receptor binding, often occurring intracellularly after signal import or at the membrane, triggers conformational changes that promote the expression of target genes, including those encoding further signal synthesis. This modular architecture ensures a reliable, density-dependent switch in cellular physiology.^[1] Threshold dynamics underpin the system's ability to generate a sharp, nonlinear response to gradual changes in population density. At low cell densities, signaling molecules are produced but diffuse away or degrade quickly, maintaining concentrations below the activation threshold and preventing premature gene induction. As density increases, the rate of production scales with cell number while diffusion losses become relatively less effective in larger, more confined populations, allowing accumulation to a critical level. This bistable-like behavior—low response at sparse densities and robust activation at high densities—filters out noise and ensures responses only when cooperative benefits outweigh individual costs.^[1]^[20] Quorum sensing provides adaptive advantages by facilitating the synchronized execution of resource-intensive or public-goods behaviors, such as those involved in virulence, motility, and nutrient acquisition, precisely when population size amplifies their efficacy. By linking gene regulation to environmental cues like density, bacteria avoid expressing costly traits in isolation, where they would confer little fitness benefit, and instead deploy them collectively to overcome barriers like host defenses or resource scarcity. This density-dependent strategy enhances survival and proliferation in diverse ecological niches.^[1] The dynamics of signal accumulation can be represented mathematically in a simplified well-mixed model as

\frac{dC}{dt} = \alpha N - \beta \frac{C}{V},

where C is the signal concentration, \alpha is the production rate per cell, N is the cell number, \beta is the effective diffusion constant, and V is the local volume. At steady state (dC/dt = 0), C = (\alpha N V)/\beta, yielding a critical density N_{\rm crit} = (\beta C_{\rm thresh})/(\alpha V), above which the threshold concentration C_{\rm thresh} is reached to trigger responses. This equation illustrates how production scales linearly with density while diffusive loss depends on concentration relative to volume, establishing the density-dependent threshold.^[20]

Signaling Molecules and Autoinducers

Quorum sensing relies on small signaling molecules known as autoinducers, which bacteria produce and release into their environment to monitor population density. These molecules exhibit remarkable chemical diversity, encompassing acyl-homoserine lactones (AHLs), oligopeptides, furanosyl borate diesters like autoinducer-2 (AI-2), and unsaturated fatty acids such as diffusible signal factor (DSF). AHLs predominate in Gram-negative bacteria and consist of a homoserine lactone ring N-acylated with a fatty acid chain varying in length from 4 to 18 carbons, often featuring a 3-oxo or 3-hydroxy substitution at the β-position of the acyl chain.^[21] The general structure can be represented as a five-membered γ-butyrolactone ring with the nitrogen atom bonded to the carbonyl of the variable-length acyl side chain (R-CO-, where R is typically an alkyl group).^[21] Oligopeptides serve as autoinducers primarily in Gram-positive bacteria, typically comprising 5 to 20 amino acids with a short leader sequence at the N-terminus that facilitates export and processing. These peptides are synthesized ribosomally as precursors and modified post-translationally, often involving cleavage of the leader sequence by extracellular proteases to yield the mature signaling form. AI-2, a key interspecies signal, features a furanosyl borate diester structure derived from (S)-4,5-dihydroxy-2,3-pentanedione (DPD), with the molecular formula C₅H₁₀BO₇⁻, where the borate bridges two hydroxyl groups on the furanose ring.^[22] DSF-family signals are cis-2-unsaturated fatty acids, exemplified by cis-11-methyl-2-dodecenoic acid (C₁₃H₂₄O₂), characterized by an α,β-unsaturated carboxyl group and variable chain lengths or branching.^[23] Biosynthesis of AHLs occurs via LuxI-family synthases, which catalyze the acylation of S-adenosylmethionine (SAM) using acyl-acyl carrier protein (acyl-ACP) as the donor, releasing the AHL and 5'-methylthioadenosine.^[21] LuxI homologs exhibit substrate specificity that determines the acyl chain length and substitution pattern of the produced AHL. For oligopeptides, synthesis involves ribosomal translation of a precursor gene, followed by export through dedicated ABC transporters and proteolytic processing to generate the active peptide. AI-2 is produced by LuxS enzymes, which convert DPD from the methionine salvage pathway into the borate diester form through spontaneous cyclization and borate complexation.^[22] DSF synthesis is mediated by crotonase-like enzymes such as RpfF, which dehydrate and isomerize fatty acid precursors like 3-hydroxydodecanoic acid to yield the cis-2-unsaturated product.^[23] Detection of these autoinducers involves specific receptor proteins that trigger downstream gene regulation. For AHLs, LuxR-type receptors bind the ligand in the cytoplasm, promoting dimerization and binding to promoter regions to activate transcription factors.^[21] Oligopeptide signals are sensed by membrane-bound histidine kinases, which autophosphorylate upon binding and transfer the phosphate to cognate response regulators, thereby modulating gene expression. AI-2 receptors, such as LuxP or LsrB, recognize the furanosyl borate structure and initiate phosphorelay cascades for interspecies coordination.^[22] DSF binds to sensor kinases like RpfC, altering their conformation to regulate transcription via response regulators.^[23] Overall, receptor specificity ensures targeted responses to autoinducer accumulation. The range and specificity of these signals vary with their physicochemical properties. Short-chain AHLs (C4-C6) are highly diffusible across membranes, facilitating intra-species communication over short distances, while longer-chain variants (C8-C14) exhibit reduced diffusion and greater species selectivity due to hydrophobic interactions with specific LuxR homologs.^[21] Oligopeptides, being hydrophilic and larger, rely on active export and localized diffusion, often promoting intraspecies signaling within biofilms. AI-2's small, polar structure enables broad interspecies detection across diverse taxa, contrasting with the more restricted profiles of AHLs and DSF, which show varying solubility influencing signal range in aqueous environments.^[22]^[23]

Bacterial Quorum Sensing

Mechanisms in Gram-Positive Bacteria

In Gram-positive bacteria, quorum sensing primarily relies on small oligopeptides, typically 5 to 16 amino acids in length, which serve as autoinducers to coordinate population-level behaviors such as virulence factor expression and competence development. These peptides are ribosomally synthesized as precursors and undergo processing and modification before export. Export occurs via dedicated ATP-binding cassette (ABC) transporters, such as ComAB in Streptococcus pneumoniae or the multifunctional AgrB in Staphylococcus aureus, which not only facilitates secretion but also catalyzes posttranslational modifications like the formation of a thiolactone ring in the autoinducing peptide (AIP) of the Agr system.^[24]^[25] This modification enhances peptide stability and specificity in the extracellular environment, where the thick peptidoglycan layer of Gram-positive cells limits passive diffusion of signals.^[24] Detection of these peptides involves two-component signal transduction systems, where membrane-bound histidine kinases act as sensors. Upon binding the extracellular peptide, the kinase autophosphorylates and transfers the phosphate group to a cognate response regulator, which then activates or represses target gene transcription. For instance, in the competence (Com) system of Bacillus subtilis and Streptococcus species, the histidine kinase ComP senses the modified ComX peptide extracellularly, phosphorylating the response regulator ComA to induce competence genes.^[26] Similarly, in some systems like certain Enterococcus pheromones, peptides may be imported via oligopeptide permeases (e.g., Opp) for intracellular modulation, though primary sensing in key Com pathways remains extracellular via kinases like ComD in S. pneumoniae.^[25]^[26] This contrasts with intracellular receptor binding in RNPP-family systems (e.g., PlcR in Bacillus thuringiensis), where imported peptides directly interact with cytoplasmic proteins without phosphorylation cascades.^[26] Prominent examples include the accessory gene regulator (Agr) system in Staphylococcus aureus, where the thiolactone-modified AIP (7-9 residues) is sensed by the histidine kinase AgrC, leading to phosphorylation of AgrA and upregulation of toxin genes during post-exponential growth.^[24] In the Com system of Streptococcus and Enterococcus species, competence-stimulating peptides (CSPs) like the 5-residue active form from ComC precursor in S. pneumoniae are exported by ABC transporters and detected by ComD, phosphorylating ComE to trigger DNA uptake machinery.^[25] These systems exemplify the peptide-based pathways unique to Gram-positives. The sensing loop begins with constitutive low-level production and export of precursor peptides, allowing extracellular accumulation proportional to cell density. Once a threshold concentration is reached—typically in the nanomolar range for AIPs—this triggers autoinduction, where activated response regulators amplify peptide gene expression, creating a positive feedback loop that synchronizes community responses.^[26]^[25] Unlike Gram-negative bacteria, where autoinducers like acyl-homoserine lactones passively diffuse across the outer membrane to bind intracellular receptors, Gram-positive mechanisms emphasize active export/import via dedicated transporters and transmembrane signaling through histidine kinases, adapting to the impermeable cell wall.^[17] This intracellular transduction via phosphorylation ensures precise, energy-dependent control over gene activation.^[17]

Mechanisms in Gram-Negative Bacteria

In Gram-negative bacteria, quorum sensing primarily relies on N-acyl homoserine lactones (AHLs) as autoinducers, which enable cell-to-cell communication through passive diffusion across the cell membrane. These signaling molecules are synthesized intracellularly by enzymes homologous to LuxI, such as the acyl-homoserine lactone synthase in the paradigmatic LuxIR system first identified in Vibrio fischeri.^[21] At low cell densities, AHLs diffuse out of the producing cells and accumulate extracellularly without active transport. As bacterial density increases, the extracellular AHL concentration rises, allowing re-entry into cells where they bind to their cognate LuxR-type receptors.^[27] The LuxIR paradigm exemplifies this process: LuxI catalyzes the formation of AHLs from S-adenosylmethionine (SAM) and acyl-acyl carrier protein (acyl-ACP), while LuxR, a transcriptional regulator, binds the AHL in the cytoplasm, undergoes a conformational change, and dimerizes. The AHL-bound LuxR dimer then binds to specific promoter regions, known as lux boxes, upstream of target genes, activating transcription of the lux operon responsible for bioluminescence in V. fischeri. This creates an autoinduction loop, where increased expression of luxI amplifies AHL production, ensuring a positive feedback that sharpens the response at high densities.^[28] Variations in the LuxIR system allow for nuanced regulation; many Gram-negative bacteria produce multiple AHLs via paralogous LuxI homologs, enabling parallel sensing circuits that integrate diverse environmental cues.^[21] Additionally, quorum quenching mechanisms counteract AHL signaling, such as the AHL-lactonase (AiiA) from Bacillus sp., which hydrolyzes the lactone ring of AHLs, rendering them inactive and preventing receptor binding.^[29] AHL signal specificity is determined by the acyl chain length, typically ranging from C4 to C14 carbons, which influences diffusion range and receptor affinity—shorter chains (e.g., C4-C6) facilitate rapid, short-distance signaling, while longer chains (e.g., C10-C14) enable broader dissemination.^[30] The presence of a 3-oxo group on the acyl chain further modulates specificity, enhancing binding to certain LuxR homologs compared to non-oxo variants.^[31] For interspecies communication, Gram-negative bacteria often integrate AHL systems with the LuxS/AI-2 pathway, where LuxS produces autoinducer-2 (AI-2), a furanosyl borate diester that diffuses and binds to distinct receptors like LuxP/QseC, facilitating crosstalk with both Gram-negative and Gram-positive species.^[32] This contrasts with the peptide-based, import-dependent systems prevalent in Gram-positive bacteria.^[21]

Notable Examples

In Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, quorum sensing is orchestrated by the hierarchical Las and Rhl systems, which utilize N-acyl homoserine lactones (AHLs) as autoinducers. The Las system employs 3-oxo-dodecanoyl homoserine lactone (3-oxo-C12-HSL) to activate the transcriptional regulator LasR, which in turn induces the expression of virulence factors such as elastase and the Rhl system. The Rhl system, activated by N-butanoyl homoserine lactone (C4-HSL), regulates additional factors including pyocyanin production, a redox-active pigment that contributes to tissue damage and iron acquisition. These coordinated responses promote biofilm formation, enhancing persistence in chronic infections like those in cystic fibrosis patients, where quorum sensing enables the bacterium to evade host defenses and resist antibiotics.^[33]^[34]^[35] The Lux quorum-sensing system in Vibrio fischeri, a marine bacterium symbiotic with the Hawaiian bobtail squid (Euprymna scolopes), exemplifies density-dependent bioluminescence. At low cell densities, the autoinducer N-3-oxohexanoyl homoserine lactone (3-oxo-C6-HSL), produced by LuxI, remains below threshold levels; upon reaching high densities within the squid's light organ, it binds LuxR to activate the lux operon, inducing luciferase expression for light production. This bioluminescence aids the host in counter-illumination camouflage against predators, while the system also regulates motility and biofilm formation to facilitate colonization and persistence in the symbiotic niche. In contrast, Vibrio cholerae employs the CAI-1 autoinducer, synthesized by CqsA, which at high densities activates the LuxO-HapR pathway to repress virulence genes and induce CTX phage lysogeny, modulating biofilm dispersal and toxin production during cholera outbreaks.^[36]^[37]^[38]^[39] In Staphylococcus aureus, a Gram-positive pathogen, the accessory gene regulator (Agr) system uses autoinducing peptides (AIPs) to control virulence through a two-component feedback loop. AIPs, processed from AgrD and exported by AgrB, bind the histidine kinase AgrC, phosphorylating the response regulator AgrA to activate RNAIII, a key effector that upregulates toxin genes (e.g., alpha-hemolysin, protein A) while repressing surface adhesins. This biphasic regulation—promoting invasion at high densities via exotoxins and aiding dissemination—underpins infections like skin abscesses and endocarditis, with the feedback cycle amplifying signal transduction for rapid population-level responses.^[40]^[41] Interspecies communication via autoinducer-2 (AI-2), produced by LuxS in both Escherichia coli and Salmonella enterica, facilitates nutrient scavenging in polymicrobial environments like the gut. AI-2 binds the Lsr receptor system, inducing the lsr operon to internalize and process the signal, which in Salmonella coordinates fucose utilization by activating metabolic genes during host colonization. This quorum-sensing circuit enhances biofilm formation and virulence gene expression, allowing these enteric pathogens to synchronize behaviors such as invasion and persistence in the intestinal niche.^[42]^[43] Myxococcus xanthus, a social soil bacterium, employs the A-signal, a set of extracellular amino acids that functions as a cell density signal, along with the C-signal, a cell surface protein, to drive multicellular fruiting body formation under starvation. These signals, sensed via two-component systems, regulate cell aggregation and sporulation, enabling coordinated motility and predation; mutants defective in A-signaling fail to initiate development.^[44]^[45] Recent studies (as of 2025) have explored quorum sensing inhibitors (QSIs) combined with antibiotics to overcome resistance in pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii, showing synergistic effects in reducing biofilm formation and virulence in hospital settings.^[46] Recent studies on Acinetobacter baumannii, a multidrug-resistant nosocomial pathogen, highlight the AbaI/AbaR quorum-sensing system using AHLs to promote carbapenem resistance. AbaI synthesizes C8-HSL and C10-HSL, which activate AbaR to upregulate efflux pumps and beta-lactamase genes, enhancing biofilm integrity and survival in hospital settings; disruption of AbaI reduces resistance profiles and virulence in 2023 isolates from intensive care units.^[47]^[48]

Archaeal Quorum Sensing

Mechanisms

Quorum sensing in archaea involves cell density-dependent communication similar to bacteria, but adapted to extreme environments like hypersaline or anaerobic conditions. Archaea produce and detect diffusible signaling molecules that accumulate with population growth, triggering coordinated gene expression. Key signaling molecules include N-acyl homoserine lactones (AHLs), often carboxylated variants unique to archaea, diketopiperazines (DKPs), and interspecies signals like autoinducer-2 (AI-2).^[49]^[50] Receptors typically include LuxR-like transcriptional regulators or two-component systems with histidine kinases, such as FilI in methanogens, which sense AHLs and activate downstream pathways. These systems form positive feedback loops, amplifying responses at high densities. Regulated behaviors encompass biofilm formation, morphological transitions (e.g., from rods to disks), motility changes, extracellular enzyme production (e.g., proteases), and metabolic processes like ammonia oxidation and carbon fixation. In marine ammonia-oxidizing archaea (AOA), QS integrates signals like AI-2, diffusible signal factor (DSF), and Pseudomonas quinolone signal (PQS) to coordinate nitrogen and carbon metabolism via genes such as amoA and accA.^[51]^[52] Recent studies as of 2024 highlight ecotype-specific QS variations, enabling interdomain crosstalk with bacteria in biofilms.^[50]

Examples

A prominent example is Haloferax volcanii, a model haloarchaeon, where QS mediates transitions from motile rod-shaped cells to non-motile disk forms at high densities. Conditioned medium containing a small-molecule signal (≤3 kDa, disk-forming signal or DFS) induces these changes, with mutants in ddfA and cirA genes failing to respond, indicating dual pathways. Proteomics revealed over 200 differentially regulated proteins, linking QS to motility and morphology adaptation in hypersaline environments. This system also shows potential for bacterial crosstalk, as the signal activates bacterial QS reporters.^[52] In Halorubrum saccharovorum, QS facilitates biofilm formation and interdomain signaling. Supernatant extracts with AHL-like or DKP activity enhance biofilm biomass (up to significant increases at 0.25–0.5 mg/mL) and influence bacterial virulence, such as boosting pyoverdine production while reducing pyocyanin in Pseudomonas aeruginosa. This suggests ecological roles in hypersaline microbial communities, with signals resistant to alkaline lactonolysis.^[51] Methanogenic archaea like Methanosaeta harundinacea employ carboxylated AHLs (e.g., 6Ac) synthesized potentially by FilI-like enzymes, promoting filamentous growth and aggregation for efficient methane production. Similarly, Halorubrum lacusprofundi correlates AHL activity with biofilm development, while Natronococcus occultus links it to protease secretion. In marine AOA such as Nitrosopumilus species, QS via AI-2 and PQS orchestrates ammonia oxidation and carbon assimilation, enhancing metabolic exchanges in ocean biofilms as demonstrated in Tara Oceans metagenomes (2024). These examples underscore QS's conservation across archaeal phyla, aiding survival in diverse niches.^[49]^[50]

Eukaryotic Quorum Sensing

In Plants

Plants produce various secondary metabolites that act as analogs to bacterial quorum sensing (QS) signals, thereby modulating microbial behavior in the rhizosphere. Isothiocyanates, derived from cruciferous plants such as those in the Brassicaceae family, interfere with acyl-homoserine lactone (AHL)-based QS in Gram-negative bacteria by degrading or mimicking these autoinducers, which reduces biofilm formation and virulence factor expression.^[53] Flavonoids, abundant in many plant species, similarly mimic AHL structures to disrupt QS signaling, promoting beneficial interactions or inhibiting pathogens by altering bacterial gene expression.^[54] These plant-derived compounds enable chemical communication that influences microbial community dynamics around plant roots.^[55] In symbiotic relationships, bacterial QS coordinates the production of Nod factors—lipochitooligosaccharides secreted by rhizobia such as Rhizobium species—to initiate nodulation in legumes. These signals are perceived by plant LysM receptor kinases, which trigger calcium oscillations and downstream gene expression for root nodule development and nitrogen fixation.^[56] QS in rhizobia ensures synchronized expression of nod genes, optimizing the timing and efficiency of symbiosis.^[57] Plants also employ LysM receptors to detect bacterial peptidoglycan fragments, activating defense responses like reactive oxygen species production and callose deposition to counter pathogenic invasions.^[58] This dual role of LysM receptors highlights their importance in distinguishing symbiotic from pathogenic microbes.^[59] Notable examples illustrate QS impacts on plant physiology. In Arabidopsis thaliana, exposure to certain AHLs inhibits primary root elongation, potentially as a defense mechanism to limit bacterial colonization. In tomatoes (Solanum lycopersicum), disrupting QS in the pathogen Ralstonia solanacearum via synthetic inhibitors reduces bacterial wilt severity by impairing motility and biofilm formation, enhancing disease resistance.^[60] Recent advancements include the use of nanomaterials to modulate plant-associated QS for agricultural benefits. Silver and zinc oxide nanoparticles interfere with AHL signaling in soil bacteria, reducing pathogen virulence while promoting beneficial microbiota, as demonstrated in crop systems for improved yield and stress tolerance.^[61] These approaches offer sustainable strategies for precision agriculture by fine-tuning microbial-plant interactions.^[62]

In Fungi

Quorum sensing in fungi involves the production and detection of small diffusible signaling molecules that enable population-density-dependent regulation of behaviors such as morphogenesis, biofilm formation, and virulence. In the opportunistic pathogen Candida albicans, farnesol serves as a key quorum-sensing molecule that accumulates extracellularly as cell density increases, inhibiting the yeast-to-hyphal transition and promoting a yeast-form morphology at high densities.^[63] This sesquiterpene alcohol diffuses freely across cell membranes and reaches threshold concentrations that trigger gene expression changes, including repression of hyphal-specific genes via the transcription factor Efg1.^[64] Similarly, tyrosol, another autoinducer in C. albicans, stimulates hyphal development and biofilm maturation during early growth phases by enhancing germ tube formation and extracellular matrix production at population thresholds.^[65] These molecules coordinate dimorphic switching, a critical phenotype for fungal adaptation and pathogenesis in infections like candidiasis, where hyphal forms contribute to tissue invasion and immune evasion.^[66] Recent advances highlight the role of oxylipins in fungal quorum sensing and their integration with bacterial signals. Oxylipins, derived from fatty acid oxidation via lipoxygenase pathways, form networks that synchronize fungal behaviors like spore germination and hyphal branching with bacterial quorum-sensing molecules, facilitating interkingdom communication in mixed biofilms.^[67] For example, in Aspergillus species, oxylipins such as psi factors regulate developmental timing in response to bacterial oxylipin autoinducers, influencing pathogenesis in host-associated microbiomes as observed in studies from 2023–2025.^[68] Additionally, nanomaterials have emerged as tools to disrupt fungal quorum sensing for antifungal therapy; silver nanoparticles interfere with farnesol and tyrosol signaling in Candida biofilms, reducing hyphal morphogenesis and virulence while enhancing susceptibility to conventional antifungals like fluconazole.^[69] These approaches target density-dependent phenotypes, offering promising strategies to combat fungal infections without broad-spectrum toxicity.^[70]

In Animals and Insects

In animals and insects, quorum sensing (QS) analogs manifest as density-dependent signaling systems, primarily through pheromones that accumulate in response to population levels, enabling coordinated social behaviors analogous to bacterial autoinduction.^[71] These mechanisms rely on volatile or contact-based chemical cues that reach threshold concentrations to elicit collective responses, such as foraging or reproductive regulation, without direct genetic exchange but via neural or hormonal pathways.^[72] Unlike prokaryotic QS, these eukaryotic systems often integrate environmental and physiological feedback, promoting group-level adaptations in terrestrial contexts.^[73] In insects, trail pheromones exemplify QS-like coordination for foraging. Argentine ants (Linepithema humile) deposit (Z)-9-hexadecenal as a trail pheromone, which accumulates along paths to food sources, guiding nestmates and amplifying recruitment as colony density increases; this signal's potency is enhanced in mixtures, ensuring efficient collective navigation.^[74] Similarly, in honey bees (Apis mellifera), queen mandibular pheromone (QMP)—a blend of five synergistic components including 9-ODA—regulates colony structure by suppressing worker reproduction and promoting nursing behaviors, with effects intensifying in high-density hives to maintain caste hierarchies.^[75] These pheromones trigger antennal detection and hormonal cascades, such as juvenile hormone modulation, mirroring QS threshold responses.^[76] Mammalian systems show parallels in immune and social signaling. In social behaviors, oxytocin exhibits density-dependent effects; elevated population densities in rodents increase oxytocin expression, reducing vigilance and promoting affiliation while modulating aggression, as seen in high-density housing experiments that alter hypothalamic oxytocin pathways.^[77] These signals bind G-protein-coupled receptors, eliciting neural responses that scale with group size.^[78] In honey bees, gut bacteria engage in interkingdom QS-like interactions, where microbial signals influence host foraging intensity and pheromone production, altering colony dynamics under stressors like pesticides.^[79] Socially, these QS analogs drive caste differentiation and swarming. In eusocial insects, pheromone thresholds determine developmental trajectories, with QMP inhibiting queen-like traits in workers to enforce division of labor. Swarming behaviors, such as ant quorum decisions for nest sites, rely on encounter-rate signals that accumulate to consensus, ensuring adaptive group relocation.^[80] These processes enhance colony resilience but are vulnerable to density perturbations.^[81]

In Aquatic Animals

Quorum sensing-like behaviors in aquatic animals involve collective decision-making and chemical signaling that enable group coordination and rapid responses to environmental threats, often integrating hydrodynamic cues from mechanosensory systems with olfactory pheromones. In schooling fish such as sardines, these behaviors facilitate synchronized swimming to evade predators, where individuals respond to nearby conspecifics through lateral line detection of water movements and chemical signals, achieving density-dependent alignment without centralized control.^[82]^[83] Studies on related species like sticklebacks demonstrate quorum decision-making, where a threshold number of informed individuals triggers group movement, enhancing information transfer across the shoal for foraging or escape.^[83] In zebrafish, injury signals exemplify chemical quorum sensing analogs, with alarm substances released from epidermal club cells upon skin damage acting as olfactory pheromones that induce density-dependent fear responses. These cues, such as hypoxanthine-3-N-oxide, elicit increased erratic swimming, freezing, and shoal tightening in conspecifics, with response intensity scaling with the number of injured donors, thereby amplifying anti-predator vigilance at higher group densities.^[84]^[85]^[86] This signaling promotes rapid aggregation and dispersal adjustments, crucial for survival in predator-rich waters. Mechanisms in aquatic environments emphasize dilution-resistant signals to counter water flow and diffusion, enabling reliable density sensing over distances. Chemical autoinducers, including peptide-based or modified acyl-homoserine lactone (AHL) analogs, maintain efficacy in turbulent conditions by leveraging hydrophobic properties or active transport, fostering density-dependent aggregation for predator avoidance.^[87] Hydrodynamic cues via lateral lines complement these, allowing fish to detect conspecific velocities and positions, integrating sensory inputs for collective behaviors like school polarization.^[82] A prominent example in marine invertebrates is the symbiosis between the Hawaiian bobtail squid (Euprymna scolopes) and Vibrio fischeri, where bacterial quorum sensing via AHL signals regulates light organ development. At high densities within the organ, V. fischeri activates LuxI/LuxR-mediated bioluminescence and induces host epithelial contractions, promoting crypt formation and daily venting cycles that maintain the mutualism for camouflage against predators.^[88] This interkingdom communication ensures bacterial persistence and host benefits, such as counter-illumination to evade detection. Recent advances highlight marine eukaryote-bacteria interkingdom signaling via AHL analogs, such as rosmarinic acid mimicking C14-HSL to enhance bacterial attachment in diatom phycospheres, influencing aggregation in aquatic food webs.^[7] Halogenated furanones from macroalgae like Delisea pulchra act as AHL antagonists, modulating bacterial colonization to reduce fouling and virulence.^[7] Hydrogel-based models simulating aquatic diffusion have further elucidated these dynamics, incorporating convection to mimic water flow and test signal robustness in fish-like group responses.^[89] Evolutionarily, these quorum sensing mechanisms enhance survival in dynamic aquatic environments by enabling adaptive group behaviors, such as synchronized predator evasion and symbiotic homeostasis, which have persisted across marine lineages to optimize resource use and reduce individual risk.^[90]^[7]

Quorum Sensing in Viruses

Mechanisms

Viruses, particularly bacteriophages, employ quorum sensing-like mechanisms to coordinate population-level behaviors such as replication strategies and host interactions, often through the production and detection of signaling molecules that accumulate with viral density. These systems enable viruses to sense environmental or host conditions and adjust gene expression accordingly, optimizing fitness in response to infection multiplicity or host population dynamics. In bacteriophages, signaling molecules include peptide-based autoinducers that regulate key decisions like the switch between lytic and lysogenic cycles. For instance, temperate phages of the SPbeta family infecting Bacillus subtilis, such as phage SPbeta, utilize short peptide signals known as arbitrium peptides (e.g., a six-amino-acid peptide) released during infection; these peptides bind to a phage-encoded receptor (AimR), repressing lytic genes at high concentrations to favor lysogeny when phage density is elevated, thereby preventing overexploitation of the host population.^[91] A core mechanism in viral quorum sensing involves density-dependent gene expression within viral populations, where signal accumulation thresholds trigger coordinated responses. In bacteriophage lambda infecting Escherichia coli, the decision between lysogeny (integration into the host genome) and lysis (host cell destruction for virion release) is governed by the multiplicity of infection (MOI), the ratio of infecting phages to host cells; higher MOI leads to greater intracellular accumulation of the cII activator protein, promoting lysogeny to ensure survival in dense infections, while low MOI favors lysis for rapid propagation.^[92] This intracellular sensing mimics quorum principles by responding to local viral density, influencing the expression of genes like cI (for lysogeny maintenance) versus Q (for lysis promotion). Such mechanisms highlight how viruses integrate population-level cues to balance immediate replication with long-term persistence. Viruses also integrate host quorum sensing pathways to fine-tune their lifecycle, hijacking bacterial communication for strategic advantage. For example, Vibrio phage VP882 encodes a receptor (VqmA) that detects the host-produced autoinducer DPO (3,5-dimethylpyrazin-2-ol), a byproduct of the bacterial LuxS-dependent quorum sensing system; at high host densities, DPO binding activates VqmA, repressing lysogeny and promoting the lytic cycle to capitalize on abundant susceptible cells, thus linking viral decisions to bacterial population status.^[93] The MOI serves as a critical threshold in these systems, where signal accumulation—whether from viral peptides or host autoinducers—must exceed a certain level to shift gene expression, ensuring coordinated infection only when viral loads are sufficient for successful dissemination. This host integration exemplifies how viruses exploit interspecies signaling without producing their own autoinducers, enhancing infectivity in polymicrobial environments.

Examples

In bacteriophages, quorum sensing enables coordinated lifecycle decisions that optimize transmission and replication within bacterial populations. A prominent example is the temperate phage VP882 infecting Vibrio cholerae, where the phage hijacks the host's quorum-sensing system by encoding a receptor, VqmA^Phage, that detects the host-produced autoinducer DPO. At low DPO concentrations, indicative of sparse host cells, the phage favors lysogeny, integrating into the host genome for latency; conversely, high DPO levels signal dense bacterial populations, promoting the lytic cycle for immediate progeny release and transmission.^[93] This mechanism ensures replication aligns with favorable host densities for efficient spread. Another classic case is the T4 bacteriophage infecting Escherichia coli, where lysis inhibition serves as an early form of density-dependent control to synchronize population-level lysis timing. Upon initial infection, superinfection by secondary phages leads to the antiholin RI inhibiting the holin T, delaying lysis by up to hours in dense infections. This inhibition increases the intracellular burst size—the number of virions released per cell—from approximately 100 to several hundred, enhancing overall phage yield when host availability is high, while avoiding premature lysis in sparse conditions.^[94] Such density-dependent communication exemplifies how phages use QS-like processes to make collective decisions on lysis timing, balancing individual replication with population survival. These examples highlight key phenotypes influenced by viral quorum sensing, particularly in modulating burst size and latency period—the time from infection to lysis. In QS-responsive phages like T4 and VP882, high signal concentrations extend latency to allow greater progeny accumulation, yielding larger burst sizes under superinfection, thereby maximizing transmission efficiency in crowded bacterial environments.^[95] Conversely, low densities trigger shorter latency for rapid dispersal, preventing resource depletion. Recent research has explored viral quorum sensing for therapeutic applications, notably in phage therapy against antibiotic-resistant bacteria. For instance, quorum sensing in Pseudomonas aeruginosa can inhibit phage infection by promoting biofilm formation; disrupting QS enhances phage adsorption and infectivity in biofilms.^[96] Similarly, understanding QS-phage interactions in V. cholerae supports strategies to synchronize lytic bursts for more effective bacterial elimination.

Interkingdom and Interspecies Interactions

Bacterial-Eukaryotic Communication

Bacterial quorum sensing (QS) signals, such as N-acyl homoserine lactones (AHLs), facilitate interkingdom communication by interacting directly with eukaryotic receptors, influencing host physiology and microbial behavior. In mammals, AHLs produced by gut bacteria bind to peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that modulates inflammation and lipid metabolism, thereby linking bacterial density to host immune responses. This interaction, first documented in eukaryotic cells exposed to bacterial QS molecules, demonstrates how AHLs can alter gene expression in host tissues, potentially exacerbating or mitigating inflammatory conditions. Similarly, plant-derived volatiles, including phenolic compounds like eugenol and methyl jasmonate, interfere with bacterial QS by degrading AHL signals or blocking receptor binding, thereby reducing pathogen virulence in plant-microbe interactions. These quenching effects highlight a bidirectional cross-talk where eukaryotic emissions disrupt bacterial communication to defend against infection. In marine ecosystems, QS-mediated interactions between bacteria and eukaryotic hosts play critical roles in symbiosis and disease dynamics. Coral-associated bacteria utilize QS signals, including those from Vibrio species, to regulate virulence factors that contribute to bleaching; for instance, quorum sensing in Vibrio coralliilyticus controls extracellular enzymes and motility, promoting algal expulsion and tissue damage under stress conditions. Conversely, beneficial bacterial symbionts in corals employ QS to enhance resistance to bleaching by stabilizing microbial communities and nutrient cycling. In marine sponges, symbionts such as Roseobacter species rely on LuxR-LuxI type QS networks to coordinate motility and biofilm inhibition, fostering stable associations that support host nutrient acquisition and defense against pathogens. These examples illustrate how QS signals enable bacteria to sense and respond to eukaryotic host cues, maintaining symbiotic balance in nutrient-limited environments. In the mammalian gut, bacterial QS molecules like autoinducer-2 (AI-2) modulate host immunity, influencing the progression of inflammatory bowel disease (IBD). AI-2, produced by diverse gut microbiota, interacts with host pattern recognition receptors to regulate cytokine production and T-cell responses, with dysregulated levels observed in IBD patients correlating to heightened inflammation and barrier dysfunction. This interkingdom signaling contributes to microbiota-host homeostasis but can drive pathogenesis when imbalanced, as seen in elevated AI-2 promoting pro-inflammatory pathways in ulcerative colitis models. Recent advances from 2023 to 2025 have explored technological interventions in interkingdom QS modulation. Nanomaterials, such as silver nanoparticles and graphene oxide, disrupt AHL synthesis and receptor interactions across bacterial-eukaryotic interfaces, offering targeted therapies for infections while preserving beneficial microbiota.^[61] In marine settings, microplastics alter QS signaling by adsorbing AHLs and fostering biofilms with enhanced QS activity, potentially amplifying pathogen virulence and disrupting symbiotic relationships in coastal ecosystems. Evolutionarily, QS signals have co-evolved with eukaryotic hosts to mediate both symbiotic and pathogenic outcomes. Ancient interkingdom signaling pathways, conserved across bacteria and eukaryotes, enable mutualistic nutrient exchange in symbioses like coral microbiomes, while in pathogens, they facilitate host invasion through synchronized virulence. This co-evolutionary arms race underscores QS as a key driver of microbial-eukaryotic adaptation, with signals like AHLs serving dual roles in cooperation and conflict.

Role in Biofilms and Multicellular Behaviors

Quorum sensing (QS) plays a pivotal role in regulating biofilm formation by coordinating the expression of genes involved in extracellular matrix production, enabling bacteria to transition from planktonic to sessile lifestyles. In Pseudomonas aeruginosa, QS systems, particularly the Las and Rhl circuits, activate the production of matrix components such as the Pel and Psl exopolysaccharides, which form the structural scaffold of the biofilm. For instance, the pel operon, responsible for glucose-rich Pel polysaccharide synthesis, is transcriptionally upregulated by the LasI/R system via 3-oxo-C12-homoserine lactone (3OC12-HSL), with mutants lacking lasI exhibiting severely reduced pel expression and flat, unstructured biofilms that fail to produce a protective matrix.^[97]^[98] Similarly, at biofilm maturity, QS triggers dispersal signals, such as those mediated by cyclic di-GMP degradation or RhlR-activated enzymes, prompting cells to release from the matrix and revert to motility, thus preventing overgrowth and nutrient depletion.^[98] This dynamic regulation ensures biofilm architecture adapts to environmental cues, enhancing persistence in hostile settings like medical devices or host tissues.^[99] Beyond biofilms, QS orchestrates multicellular behaviors that promote collective survival and resource exploitation. In Myxococcus xanthus, the A-signal, an amino acid-based autoinducer produced under starvation, functions as a density sensor to initiate fruiting body formation, where cells aggregate into mounds, differentiate into spores, and develop complex multicellular structures for dispersal.^[100] This process requires a minimum cell density of approximately 10^9 cells/mL, with asg gene mutants defective in A-signal production failing to progress beyond early aggregation stages.^[100] QS also governs swarming motility, a coordinated flagellar-driven migration on surfaces, as seen in Salmonella enterica, where high-density signaling facilitates rapid colony expansion and invasion.^[101]^[102] These behaviors exemplify how QS enables bacteria to behave as multicellular entities, optimizing predation, nutrient scavenging, and evasion of stresses.^[101] Interspecies interactions within polymicrobial communities further highlight QS's role in synchronizing biofilm dynamics through shared signals like autoinducer-2 (AI-2). AI-2, produced by the LuxS enzyme across diverse Gram-positive and Gram-negative bacteria, diffuses freely and modulates matrix gene expression in mixed biofilms, promoting adhesion and structural integrity among cohabiting species.^[103] For example, in oral or enteric consortia, AI-2 from Escherichia coli enhances Porphyromonas gingivalis biofilm formation by upregulating adhesin genes, while in Streptococcus gordonii communities, it coordinates polysaccharide synthesis for communal matrix stability.^[103] This interspecies crosstalk fosters resilient polymicrobial structures, amplifying community-level adaptations like virulence factor secretion.^[103] Recent studies, particularly from 2024 onward, have elucidated QS in anaerobic bacteria within gut biofilms, revealing its contribution to community stability and pathogenesis. In the anaerobic gut environment, AI-2-mediated QS in Clostridium difficile induces biofilm growth via prophage activation and extracellular DNA release, enhancing adhesion to mucosal surfaces.^[104] Similarly, in Clostridium perfringens, LuxS/AI-2 regulates toxin production and biofilm maturation, with quorum quenching agents like reuterin disrupting these processes to reduce virulence.^[104] Regarding resistance spread, QS facilitates horizontal gene transfer in polymicrobial gut biofilms, where high-density signaling promotes conjugative plasmid exchange among anaerobes, accelerating antibiotic resistance dissemination; quorum quenching has been shown to mitigate this by lowering biofilm-induced resistance rates.^[104] These insights underscore QS's role in anaerobic polymicrobial dynamics, with implications for gut dysbiosis and chronic infections.^[104] Mathematical models have been instrumental in simulating QS-driven biofilm gradients, often employing reaction-diffusion equations to capture signal propagation and spatial heterogeneity. A key model integrates biomass growth, EPS production, and AHL diffusion within a one-dimensional biofilm domain, where the autoinducer concentration A(x,t) follows a reaction-diffusion equation:

\frac{\partial A}{\partial t} = D_A \frac{\partial^2 A}{\partial x^2} + r_M M - \delta_A A,

with D_A as the diffusion coefficient (e.g., 0.26 m²/day in biofilm), r_M the production rate proportional to biomass density M, and \delta_A degradation; QS activates EPS synthesis when A > \tau (threshold ~10 nM), leading to nonlinear density-dependent diffusion for biomass expansion.^[105] Such models predict signal gradients that delay QS activation in biofilm depths, influencing matrix distribution and dispersal timing, and have been validated against P. aeruginosa experiments.^[105] These simulations provide conceptual frameworks for understanding QS spatiotemporal control in complex communities.^[105]

Quorum Sensing Inhibition

Quorum Quenching Mechanisms

Quorum quenching mechanisms encompass biological processes that disrupt quorum sensing (QS) signals, thereby interfering with bacterial communication and collective behaviors. These mechanisms primarily target the production, stability, or reception of autoinducers such as N-acyl homoserine lactones (AHLs) and autoinducer-2 (AI-2), preventing the activation of QS-regulated genes.^[18] Naturally occurring and engineered approaches have been identified across prokaryotes and eukaryotes, highlighting QQ as a widespread ecological strategy to modulate microbial populations.^[106] Enzymatic degradation represents a primary QQ mechanism, where enzymes hydrolyze or modify autoinducer structures to render them inactive. Lactonases, such as the Bacillus sp. AiiA enzyme, catalyze the hydrolysis of the lactone ring in AHLs, opening the ring and preventing receptor binding; this process alters the molecule's conformational structure, effectively silencing QS signals in Gram-negative bacteria.^[107] Similarly, amidases (also known as acylases) cleave the amide bond between the acyl chain and the homoserine lactone moiety of AHLs, producing a free fatty acid and homoserine lactone, which disrupts signaling in pathogens like Pseudomonas aeruginosa.^[106] These enzymes belong to distinct superfamilies, with AiiA-like lactonases featuring a metal-binding motif (HXHXDH) essential for catalysis.^[108] Receptor antagonism involves molecules that bind to QS receptors without triggering downstream responses, thereby blocking autoinducer activation. Halogenated furanones, derived from the marine alga Delisea pulchra, exemplify this approach by competitively binding to LuxR-type receptors in Gram-negative bacteria, leading to accelerated degradation of the receptor-autoinducer complex rather than stabilization.^[109] This antagonism destabilizes the transcriptional activator, inhibiting QS-regulated virulence and biofilm formation without directly degrading signals.^[21] Biosynthesis inhibition targets the enzymes responsible for autoinducer production, halting signal accumulation at the source. Inhibitors can block LuxI homologs, which synthesize AHLs in Gram-negative bacteria, by interfering with their catalytic activity and preventing acyl chain transfer to S-adenosylmethionine-derived precursors.^[110] For AI-2-based QS, prevalent in both Gram-positive and Gram-negative species, suppression of LuxS enzyme activity disrupts the conversion of S-ribosylhomocysteine to the AI-2 precursor, limiting interspecies signaling.^[21] QQ mechanisms occur naturally in diverse organisms, underscoring their role in microbial ecology and host defense. Eukaryotic enzymes, such as mammalian serum lactonases, hydrolyze AHLs with broad specificity, contributing to innate immunity against bacterial infections.^[111] Plant-derived paraoxonase-1 (PON1) exhibits lactonase activity that degrades AHLs produced by soil pathogens, protecting roots from QS-mediated colonization. Additionally, bacteriophages encode QQ proteins, such as the anti-activator Aqs1 in Pseudomonas phage DMS3, which inhibits LuxR homologs to modulate host QS during infection and favor lysogeny.^[113] Recent advances have expanded QQ applications to complex environments, including anaerobic biofilms where QQ enzymes like acylases reduce electroactive biofilm development by degrading AHLs and AI-2, thereby limiting microbial adhesion and metabolic synchronization.^[114] In 2024, AI-2-specific quenchers targeting LsrK kinase were developed, inhibiting AI-2 phosphorylation and receptor activation in enteric bacteria, offering targeted disruption of interspecies QS without broad-spectrum effects.^[115]

Inhibition Strategies

Inhibition strategies for quorum sensing (QS) primarily target the disruption of bacterial communication pathways without directly killing cells, thereby reducing virulence and biofilm formation while minimizing the evolution of resistance. These approaches encompass molecular mimicry, enzymatic degradation, and structural modifications of signaling molecules, often drawing from synthetic chemistry and natural products. Recent innovations integrate these tactics with advanced delivery systems and combinatorial therapies to enhance efficacy in complex environments. Mimicry-based strategies involve the design of agonist or antagonist analogs that compete with native autoinducers for receptor binding, thereby blocking QS activation. For instance, the synthetic furanone derivative C-30 acts as an antagonist of the LasR receptor in Pseudomonas aeruginosa, inhibiting the expression of QS-regulated virulence factors such as pyocyanin and elastase by promoting LasR degradation and preventing DNA binding.^[116] This compound has demonstrated a five-fold reduction in bacterial growth in nutrient-limited conditions and attenuated biofilm formation in murine lung infection models at doses of 1-2 µg/g body weight.^[117]^[118] Other analogs, like N-decanoyl-L-homoserine benzyl ester and thiolactones, similarly mimic acyl-homoserine lactones (AHLs) to block LasR and related receptors, reducing elastase production and rhamnolipid synthesis in P. aeruginosa by up to 80%.^[119]^[120] Degradation strategies focus on breaking down QS signals through enzymatic or chemical means to prevent signal accumulation. Enzyme delivery systems, such as acylase (e.g., AiiD or PvdQ), hydrolyze the amide bonds of AHLs, irreversibly degrading signals like 3-oxo-C12-HSL and thereby suppressing QS-dependent phenotypes including pyocyanin production and biofilm maturation in P. aeruginosa. Natural products complement these efforts; ajoene, a sulfur-rich vinyl dithiins compound derived from garlic, inhibits QS by reducing AHL production and downregulating genes under LasR and RhlR control, resulting in reduced biofilm formation and virulence factor expression in P. aeruginosa.^[121]^[122]^[120] Delivery of acylase via encapsulation has shown up to 90% reduction in biofilm biomass in vitro.^[121] Modifications of QS signals involve subtle chemical alterations to analogs that bind receptors but fail to activate transcription, often by changing receptor conformation. For example, AHL analogs like compound 11f compete with 3-oxo-C12-HSL for LasR binding in P. aeruginosa, inducing non-functional conformational changes that inhibit pyocyanin production by 34.5% and biofilm formation by 36.2% at 200 µM concentrations.^[121]^[120] Similarly, modifications to AI-2 precursors, such as LuxS inhibitors (e.g., certain peptides and furanones), disrupt signal synthesis and alter LuxR/S receptor interactions, attenuating QS in Gram-positive and Gram-negative bacteria. These targeted changes preserve signal recognition while blocking downstream signaling, offering specificity over broad-spectrum antimicrobials.^[121]^[120] As of 2025, recent advances emphasize engineered delivery platforms to improve the bioavailability and targeted release of QS inhibitors (QSIs). Nanomaterial carriers, such as solid lipid nanoparticles and silver nanoparticles (AgNPs), encapsulate QSIs to enhance penetration into biofilms, achieving up to seven-fold greater inhibition of PqsR antagonists in P. aeruginosa compared to free compounds.^[121] Hydrogel encapsulation enables slow-release quenching; for instance, mussel-inspired hydrogels loaded with furanone and metal-organic frameworks (MOFs) provide sustained QSI delivery on stainless steel surfaces, reducing P. aeruginosa biofilm adhesion by over 95% in marine antifouling applications.^[61] Although research on microplastic-derived inhibitors remains emerging, plastic-associated microbial communities have yielded novel QS-disrupting metabolites from degrading bacteria, such as halogenated compounds that inhibit AHL signaling in environmental biofilms.^[123] Combinatorial strategies pair QS inhibition with antibiotics to exploit synergies and curb resistance development. QSIs combined with tobramycin restore susceptibility in multidrug-resistant P. aeruginosa by dismantling biofilms and enhancing antibiotic penetration.^[121] Similarly, furanone C-30 with tobramycin has been shown to enhance efficacy against hospital-acquired infections. These approaches lower selective pressure on bacteria, as QS disruption attenuates virulence without bactericidal effects, slowing resistance spread in polymicrobial settings.^[124]

Applications in Medicine and Biotechnology

Quorum sensing inhibitors (QSIs) have emerged as promising antivirulence agents in medicine, particularly for treating chronic infections caused by Pseudomonas aeruginosa in cystic fibrosis (CF) patients, where QS regulates biofilm formation and virulence factor production, exacerbating lung damage.^[125] In preclinical models, QSIs such as RNAIII-inhibiting peptide (RIP) have attenuated P. aeruginosa virulence by disrupting the las and rhl QS systems, promoting bacterial clearance by the host immune response without directly killing the bacteria.^[116] Recent studies have demonstrated synergistic effects when QSIs are combined with conventional antibiotics, enhancing efficacy against hospital-acquired infections like those from multidrug-resistant P. aeruginosa; for instance, a 2025 investigation identified QSIs that resensitize bacteria to antibiotics, reducing minimum inhibitory concentrations by up to 50% in vitro.^[126] This approach targets QS-regulated efflux pumps and biofilms, which contribute to resistance, offering a strategy to combat persistent infections in clinical settings.^[127] In biotechnology, QS modulation enables biofilm control in water treatment systems, where inhibiting QS prevents the formation of problematic bacterial communities on surfaces and pipes, improving disinfection efficiency and reducing corrosion.^[128] For example, enzymes like acylase I degrade N-acyl homoserine lactones (AHLs), key QS signals, disrupting biofilm maturation in wastewater biofilms dominated by Gram-negative bacteria.^[129] Additionally, engineering QS pathways in microbial consortia enhances fermentation processes; in Escherichia coli-based production, synthetic QS circuits increase acid tolerance and yield organic acids like succinic acid by coordinating population-level responses to stress, achieving up to 20% higher titers in fed-batch fermentations.^[130] These applications leverage QS to optimize industrial bioprocesses, such as biofuel and pharmaceutical precursor synthesis, by synchronizing metabolic outputs across cell populations.^[131] In agriculture, QS quenching strategies prevent plant diseases by interfering with pathogenic bacteria's ability to coordinate virulence; for instance, Bacillus species with quorum-quenching lactonases reduce pathogenicity of Pectobacterium carotovorum on potato tubers by degrading AHL signals.^[132] This biocontrol method minimizes chemical pesticide use while preserving beneficial microbiomes. Symbiotic enhancement via QS involves promoting nitrogen-fixing interactions in rhizobia-legume symbioses, where QS regulates nod gene expression for nodule formation; modulating AHL production can enhance nodulation in soybean fields, boosting nitrogen uptake and yield.^[133] By 2025, computational approaches have accelerated QSI discovery, with early-phase trials exploring QQ for chronic wounds. Phage therapy integrated with QS modulation enhances efficacy; inhibiting QS in Klebsiella pneumoniae increases phage susceptibility by downregulating anti-phage defenses, achieving 90% bacterial reduction in murine infection models.^[134] Furthermore, QSIs slow the spread of antibiotic resistance in infections, as resistance mutations impose fitness costs that limit propagation during host colonization, unlike direct-killing antibiotics.^[135] Despite these advances, challenges persist in QSI applications, including achieving specificity to target pathogenic QS without disrupting commensal microbiota and ensuring effective in vivo delivery, where poor bioavailability and rapid degradation limit therapeutic concentrations at infection sites.^[136] Nanoparticle encapsulation has shown promise for sustained release, but clinical translation requires addressing immune interactions and long-term safety.^[137]

Advanced Applications

Synthetic Biology

Synthetic quorum sensing (QS) systems in biology leverage engineered genetic circuits to enable population-level control of gene expression, often adapting the LuxIR module from natural bacterial communication where LuxR transcription factors respond to acyl-homoserine lactone (AHL) signals to activate promoters. LuxR-based switches have been pivotal for designing population density-dependent behaviors, such as synchronized gene induction in Escherichia coli, allowing precise regulation of cell growth and metabolic outputs through feedback loops that maintain stable population densities.^[138] These systems facilitate applications in biotechnology by coupling QS to downstream effectors, enabling scalable control without external inputs.^[139] Orthogonal AHL systems expand the toolkit by minimizing crosstalk between multiple QS modules, permitting parallel signaling pathways within the same cell or community.^[140] This orthogonality supports complex circuit designs, such as layered logic operations, and has been validated in high-throughput screens showing negligible cross-activation across AHL variants, though some interactions between components like LasR and EsaI/EsaR have been noted.^[141] Key tools include the QuorumR repressible promoter, a LuxR variant that inverts QS logic to suppress gene expression at high densities, providing negative feedback for robust bistability in circuits.^[142] For interspecies applications, AI-2 circuits—based on the LuxS-produced autoinducer-2 signal—enable cross-kingdom communication in synthetic consortia, as seen in engineered communities where AI-2 modulates collective behaviors like biofilm formation across Gram-positive and Gram-negative strains.^[143] These circuits have been integrated into probiotic consortia for targeted drug delivery, where QS synchronizes payload release in response to environmental cues like pH or hypoxia, achieving coordinated dispersal in mammalian models. Recent 2025 advances include hybrid QS-machine learning systems that enhance predictive control in synthetic biology for applications like personalized medicine.^[144]^[145] QS toggle switches combine bistable elements with signaling to implement logic gates, such as AND/OR functions for decision-making in populations, where AHL inputs flip states to control outputs like fluorescence or antibiotic resistance.^[146] Design principles emphasize tunable thresholds, achieved by varying promoter strength—stronger promoters lower activation density by enhancing LuxR affinity, while libraries of mutated operators allow fine-tuning of sensitivity for applications in metabolic engineering.^[147] Recent advances as of 2025 integrate QS with nanomaterials for smart materials, where AHL-responsive bacteria embedded in nanoparticle matrices enable self-regulating adhesion and release, mimicking adaptive surfaces.^[148] Hydrogel-based synthetic biofilms, engineered with QS circuits, form dynamic structures that respond to density signals for controlled degradation or growth, advancing tissue engineering scaffolds.^[149]

Engineering and Computing

In engineering and computing, quorum sensing (QS) principles have inspired decentralized control systems that mimic bacterial density-dependent signaling to enable robust, scalable coordination without central authority. These bio-inspired approaches leverage local communication and threshold-based responses to achieve emergent behaviors in artificial systems, drawing from the diffusion of autoinducers like acyl-homoserine lactones (AHLs) in natural QS. Such models promote fault-tolerant operations in dynamic environments, where agents detect local "density" through signals and trigger collective actions only upon reaching critical thresholds.^[150] In robotics, QS-like mechanisms facilitate swarm coordination by simulating diffusive signal propagation for decentralized decision-making. For instance, Kilobot platforms, low-cost miniature robots, employ short-range infrared communication to emulate QS, allowing swarms to adapt to environmental changes such as obstacles or task reallocations through local density feedback. This constrained communication enhances adaptability, as demonstrated in experiments where swarms of dozens to hundreds of units self-organize into formations or explore spaces more efficiently than with long-range signaling; the platform has demonstrated scalability to 1,000 units in self-assembly tasks.^[150]^[151] Recent advances, including 2025 implementations using diffusive scalar probes for quorum sensing in exploration tasks, enable robots to select motion primitives based on local gradients, reducing planning time by integrating density-based error correction to maintain swarm integrity during faults. These systems exemplify threshold voting, where a robot "votes" to initiate actions only if sufficient neighbors signal agreement, mirroring bacterial competence induction.^[150]^[152] QS models have also influenced distributed computing algorithms, particularly for clustering and consensus in networks. Inspired by QS's non-specific, global-yet-local signaling, algorithms treat data points or nodes as "cells" that accumulate virtual autoinducers based on connectivity, forming clusters when local densities exceed thresholds. A seminal example is the quorum sensing-inspired dynamic clustering algorithm, which uses local neighbor knowledge to partition data into colonies without global oversight, achieving quadratic convergence and robustness to noise through density feedback mechanisms. In chemical computing paradigms, AHL analogs serve as tunable signals in non-biological reaction networks, enabling molecular-scale distributed processing; for instance, emulsion droplet swarms exhibit QS-like quorum formation at water surfaces, where chemical signals drive clustering above critical densities for emergent computation. These approaches incorporate error correction via feedback loops that amplify or dampen signals based on population thresholds, ensuring reliable outcomes in noisy chemical environments.^[153]^[154] In materials engineering, QS principles guide the design of self-assembling structures for sensing applications, where signal diffusion triggers hierarchical organization. Engineered systems using QS-inspired chemical networks promote the formation of responsive materials, such as self-assembling peptide networks that function as molecular logic gates; these networks detect input densities through AHL-like binding and output conformational changes, enabling Boolean operations like AND/OR gates at the nanoscale. For sensors, QS-mimicking biofilms—programmed via orthogonal signaling—self-assemble into functional layers that detect analytes through density-dependent aggregation, as seen in curli fiber-based materials that integrate QS cues for tunable mechanical properties.^[155] Analogies to threshold voting extend here, with density feedback providing error correction in material responses, preventing premature assembly or disassembly under variable conditions. Recent 2025 work on quorum-sensing active matter highlights phase transitions and collective dynamics inspired by QS for potential applications in adaptive materials.^[156]

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Quorum sensing in bacteria: the LuxR-LuxI family of cell density ...
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The term “quorum sensing” was introduced by Dr. Steven Winans in 1994, who was putting together one of the first review articles on autoinduction in bacteria. ...
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[PDF] A Mathematical Model for Quorum Sensing in Pseudomonas ...
In summary, quorum sensing can be accomplished by increasing the density of a colony of fixed size, or by increasing the size of a colony of large enough ...
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Numerous species of bacteria employ a mechanism of intercellular communication known as quorum sensing. This signaling process allows the cells comprising a ...
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Gram-positive bacteria coordinate social behavior by sensing the extracellular level of peptide signals. These signals are biosynthesized through divergent ...
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Genetic and Structural Analyses of RRNPP Intercellular Peptide ...
Intercellular chemical communication (quorum sensing) provides a means to coordinate gene expression and behavior among bacteria. By coordinating behaviors, ...Rrnpp Structure-Function · Rap Proteins Use Catalytic... · Literature Cited<|control11|><|separator|>
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Quorum-sensing in Gram-negative bacteria - Oxford Academic
Therefore, the term 'quorum-sensing' has been coined to describe this ability of bacteria to monitor cell density before expressing a phenotype. In this ...<|control11|><|separator|>
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Microbial Primer: LuxR-LuxI Quorum Sensing - PMC - NIH
A monomeric LuxI homolog catalyses the synthesis of an AHL from an activated organic acid and SAM. ... LuxR homologs, which do not have a cognate LuxI homolog.
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Quenching Quorum-Sensing-Dependent Bacterial Infection by an N ...
Here we show that the acyl-homoserine lactonase (AHL-lactonase), a new enzyme from Bacillus sp., inactivates AHL activity by hydrolysing the lactone bond of ...
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Molecular basis for the substrate specificity of quorum signal ... - PNAS
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Specificity of Acyl-Homoserine Lactone Synthases Examined by ...
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Regulatory Mechanisms of the LuxS/AI-2 System and Bacterial ...
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The strongest autoinducer, called CAI-1 (for cholera autoinducer-1), was previously identified as (S)-3-hydroxytridecan-4-one.Missing: CTX phage
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Genetic and Phenotypic Diversity of Quorum-Sensing Systems in ...
Two autoinducer molecules are important for quorum sensing in V. cholerae. These two molecules are cholera autoinducer 1 (CAI-1), a molecule of undetermined ...
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Regulation of virulence in Staphylococcus aureus - PubMed Central
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Quorum sensing in Escherichia coli and Salmonella - ScienceDirect
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Regulation of AI-2 Uptake and Processing in E. coli
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Mar 14, 2017 · The developmental program which results in fruiting body formation involves three chemically characterized intercellular signals. The A-signal ...
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Signaling in myxobacteria - PubMed - NIH
Early in development, the quorum-sensing A-signal in Myxococcus xanthus helps to assess starvation and induce the first stage of aggregation. Later, the ...
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Impact of AbaI mutation on virulence, biofilm development, and ...
Sep 14, 2024 · Several studies have investigated the influence of the quorum sensing system, including abaI, abaR, and abaM, on the pathogenicity of A.
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Co-regulation of biofilm formation and antimicrobial resistance in ...
Oct 28, 2023 · The quorum sensing system AbaI/AbaR is known to contribute to biofilm formation and antibiotic resistance in A. baumannii [110, 112]. Exogenous ...
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Insights into the mechanism of action of the arbitrium communication ...
Jun 24, 2022 · The arbitrium system is employed by phages of the SPbeta family to communicate with their progeny during infection to decide either to follow the lytic or the ...
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Widespread Utilization of Peptide Communication in Phages ... - NIH
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Phage reproduction depends on bacterial host cells, and thus it is critical for temperate phages to modulate their reproduction strategy in response to host ...
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Look Who's Talking: T-Even Phage Lysis Inhibition, the Granddaddy ...
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Communication between Viruses Guides Lysis–Lysogeny Decisions
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Phage Therapy as a Novel Alternative to Antibiotics Through ...
Oct 17, 2025 · Quorum sensing inhibits phage infection by regulating biofilm formation of P. aeruginosa PAO1. J. Virol. 2025;99:e01872-24. doi: 10.1128/jvi ...
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Quorum sensing inhibits phage infection by regulating biofilm ...
Dec 31, 2024 · Our findings suggest that the inhibition of QS may enhance phage infectivity, potentially facilitating advanced phage therapy combined with QS interference.
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Plant-Derived Natural Products as Sources of Anti-Quorum Sensing ...
May 13, 2013 · Not only to plants produce mimicry molecules that are anti-QS, but certain plant parts such as pea (Pisum sativum) seedlings [17] also produce ...
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Plant-Derived Inhibitors of AHL-Mediated Quorum Sensing in Bacteria
Nov 8, 2019 · This review focused on the most significant groups of plant-derived QS inhibitors and well-studied individual compounds for which in silico, in vitro and in ...
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Quorum sensing interference by phenolic compounds – A matter of ...
In fact, the main source of natural quorum sensing inhibitors (QSIs) are plants, including vegetables, fruits, roots, rhizomes, flowers, leaves, and seeds [1].
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Quorum Sensing in Nitrogen-Fixing Rhizobia - PMC
Quorum sensing plays a major role in preparing and perhaps coordinating the symbiotic nitrogen-fixing rhizobia during the establishment of their interactions ...
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Plant growth-promoting activity and quorum quenching-mediated ...
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Here we show that PGN sensing and immunity to bacterial infection in Arabidopsis thaliana requires three lysin-motif (LysM) domain proteins.
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Molecular basis for bacterial peptidoglycan recognition by LysM domains. ... Plant recognition of symbiotic bacteria requires two LysM receptor-like kinases.<|control11|><|separator|>
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Oct 14, 2022 · N-acyl-homoserine lactones (AHLs) are used as quorum-sensing signals by Gram-negative bacteria, but they can also affect plant growth and
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Quorum Sensing Inhibition Attenuates the Virulence of the Plant ...
Nov 10, 2020 · These compounds may function as the basis for the development of QS inhibitors to combat the bacterial wilt disease caused by RSSC strains.
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Nanomaterials Regulate Bacterial Quorum Sensing: Applications ...
Feb 13, 2024 · ... quorum sensing in the signal supply and ... nanomaterial drug delivery efficiency, thereby affecting nanomaterial QS regulatory activity.
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Oct 20, 2025 · Nano-enabled agrochemicals (NEAs) can selectively modulate root microbiome composition and function through various mechanisms: (1) direct ...
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Physiological adventures in Candida albicans: farnesol and ...
Mar 4, 2024 · Farnesol was first identified as a quorum-sensing molecule, which blocked the yeast to hyphal transition in Candida albicans, 22 years ago.
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Candida albicans Czf1 and Efg1 Coordinate the Response to ...
Quorum sensing by farnesol in Candida albicans inhibits filamentation and may be directly related to its ability to cause both mucosal and systemic diseases.
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Mar 29, 2004 · The active component of conditioned medium is tyrosol, which is released into the medium continuously during growth.
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Interactions between Bacteria and Aspergillus fumigatus in Airways
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Growth of Aspergillus fumigatus in Biofilms in Comparison to ... - NIH
Jan 4, 2022 · Quorum sensing mechanisms could affect biofilm ... Aspergillus fumigatus biofilm reveals enhanced production of the mycotoxin gliotoxin.
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Unlocking fungal quorum sensing: Oxylipins and yeast interactions ...
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Exploring Oxylipins in Host–Microbe Interactions and Their Impact ...
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A Critical Review on Sustainable Formulation of Anti-quorum ...
Jan 2, 2025 · This study delves into the nanotechnology idea for the formulation of natural-based anti-quorum-sensing agents, particularly Candida ...
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Nanoparticles Targeting Biofilms: A New Era in Combating ...
Oct 25, 2025 · Quorum sensing (QS) is the well-studied mechanism of communication in bacterial pathogens that regulates adhesion, EPS production, biofilm ...
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Immunoregulation via Cell Density and Quorum Sensing-like ...
Aug 6, 2022 · In this review, we explore and discuss potential QS-like mechanisms deployed by the immune system to coordinate cellular-level responses.
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Sep 9, 2025 · In the Argentine ant (Linepithema humile), for instance, exposure to (Z)-9-hexadecenal – a trail pheromone component that induces trail- ...
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Jan 15, 2025 · Microplastics were associated with microbial quorum sensing and transporter systems. •. Microplastics were correlated with microplastic ...
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Quorum sensing by encounter rates in the ant Temnothorax albipennis. ... Nature versus nurture in social insect caste differentiation. Trends in ...
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(PDF) Ratio-dependent quantity discrimination in quorum sensing ants
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May 15, 2024 · In particular, fish use both vision and their lateral lines to sense each other, but it is unclear how much they rely on information from these ...
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Quorum decision-making facilitates information transfer in fish shoals
May 12, 2008 · We show that a quorum response to conspecifics can explain how sticklebacks make collective movement decisions, both in the absence and presence ...
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Zebrafish significantly changed their behavior in response to the presentation of alarm substance. Most robust among these changes was the increase of erratic ...
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Apr 8, 2024 · Most freshwater fishes display olfactory alarm reactions in which an injured fish releases putative alarm substances from the skin to notify ...
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The number of conspecific alarm substance donors notably ...
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Emergent robustness of bacterial quorum sensing in fluid flow - PMC
... threshold concentration, typically associated with an increasing cell density (1). ... where ∇ 2 A represents AI diffusion, q is the base production rate ...
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Bacterial Quorum-Sensing Regulation Induces Morphological ...
This work broadens our concept of how quorum sensing can regulate host development, thereby allowing bacteria to maintain long-term tissue associations.
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May 10, 2020 · By incorporating a convection term as a means of local flow and evaporation induction to the hydrogel based model, we simulated the experimental ...
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Quorum Sensing Regulates Bacterial Processes That Play a Major ...
An Increasing Focus on Quorum Sensing Signals in Marine Studies. Marine bacteria constantly compete for ecological niches, C and nutrients, giving rise to many ...
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The Involvement of Cell-to-Cell Signals in the Development of a Bacterial Biofilm
### Summary of Key Findings on Quorum Sensing in *Pseudomonas aeruginosa* Biofilm Formation
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Quorum-Sensing Regulation of the Biofilm Matrix Genes (pel) of ...
Quorum sensing (QS) has been previously shown to play an important role in the development of Pseudomonas aeruginosa biofilms (D. G. Davies et al., ...
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Bacterial quorum sensing in complex and dynamically changing ...
In this Review, we highlight new findings concerning how bacteria deploy quorum sensing in realistic scenarios that mimic nature.
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A Myxococcus xanthus cell density-sensing system required for ...
Progression through early Myxococcus xanthus multicellular fruiting body development requires the generation of and response to extracellular A signal.
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Quorum sensing and swarming migration in bacteria
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Swarming populations of Salmonella represent a unique ... - NIH
In some organisms, swarming is controlled by quorum sensing, and in others, swarming has been shown to be coupled to increased expression of important virulence ...
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AI-2-mediated signalling in bacteria - Oxford Academic
In the late 1990s, autoinducer-2 (AI-2) was shown to induce bioluminescence in Vibrio harveyi cultures; remarkably, AI-2 production was detected in diverse Gram ...
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Understanding Quorum-Sensing and Biofilm Forming in Anaerobic ...
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A mathematical model of quorum sensing regulated EPS production ...
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Quorum Quenching Revisited—From Signal Decays to Signalling ...
An AHL acylase, also known as AHL amidohydrolase, cleaves the peptide (amide) bond of the lactone ring to release a fatty acid and homoserine lactone ...Missing: amidases | Show results with:amidases
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Quorum Quenching: Enzymatic Disruption of N-Acylhomoserine ...
These enzymes, termed AiiA lactonases, hydrolyze the lactone bond within the AHL moiety, thus changing the relative conformational structure of the signaling ...
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The exceptionally efficient quorum quenching enzyme LrsL ...
Aug 21, 2022 · AiiA was the first AHL lactonase discovered belonging to the MBL superfamily. It possesses a characteristic HXHXDH motif that binds two metal ...
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Halogenated furanones inhibit quorum sensing through ... - PubMed
This suggests that halogenated furanones modulate LuxR activity but act to destabilize, rather than protect, the AHL-dependent transcriptional activator.Missing: receptor antagonism
[109]
Quorum sensing interference by phenolic compounds – A matter of ...
In AHL-mediated QS systems, QSI can act by (i) inhibition of AHL synthesis, by interacting with LuxI-type AHL synthases; (ii) degradation or inactivation of ...
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Quorum quenching enzyme activity is widely conserved in the sera ...
AHL inactivation activity, with a lactonase-like enzyme, is conserved in the serum of all 6 tested mammalian animals.
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Quorum Quenching Effect of Recombinant Paraoxonase -1 Enzyme ...
Quorum quenching inhibits QS system providing means of fighting P. aeruginosa infections. •. Quorum quenching enzymes such as paraoxonase enzyme activity ...
[112]
Article A phage-encoded anti-activator inhibits quorum sensing in ...
Feb 4, 2021 · In this work, we show that Pseudomonas phage DMS3 encodes a quorum-sensing anti-activator protein, Aqs1, which is expressed immediately ...
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Quorum quenching inhibits the formation and electroactivity of ...
Feb 1, 2025 · This study explored the effects of quorum quenching (induced by adding acylase) on electrogenic biofilm development and its underlying mechanisms.
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New LsrK Ligands as AI-2 Quorum Sensing Interfering Compounds ...
Oct 9, 2024 · In this study, newly designed autoinducer-2 (AI-2)-inspired compounds in targeting biofilm-associated infections were evaluated for their ability to inhibit ...
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A quorum-sensing inhibitor blocks Pseudomonas aeruginosa ...
Oct 18, 2013 · In this study, we prepare synthetic molecules and analyze them for inhibition of the Pseudomonas quorum-sensing receptors LasR and RhlR.
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Association of furanone C-30 with biofilm formation & antibiotic ...
This study was aimed to explore the association of furanone C-30 with biofilm formation, quorum sensing (QS) system and antibiotic resistance in P. aeruginosa.
[117]
Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle ...
AHL Analogs. The chemical structure of AHL analogs (lactone ring and acyl side chain) is the main factor influencing cell-to-cell communication via AHL signals.
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Strategies for quorum sensing inhibition as a tool for controlling ...
This review highlights the approaches reported so far for disrupting different steps of the QS system of the multiresistant pathogen Pseudomonas aeruginosa.
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Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes ...
Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Tim Holm Jakobsen
[120]
Antifouling Mussel-Inspired Hydrogel with Furanone-Loaded ZIF-8 ...
Jun 18, 2025 · This study reports the development of a hydrogel-metal-organic framework (MOF)-quorum sensing inhibitor (QSI) antifouling coating on 304 stainless steel (SS) ...
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Research Progress on the Combination of Quorum-Sensing ... - MDPI
Apr 8, 2024 · Fortunately, when QSIs are combined with antibiotics, they have a better therapeutic effect, and it has even been demonstrated that the two ...
[122]
Quorum Sensing as Antivirulence Target in Cystic Fibrosis Pathogens
In this review we describe the pathogens most commonly associated with CF lung infections: Staphylococcus aureus, Pseudomonas aeruginosa, species of the ...
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Attenuation of Pseudomonas aeruginosa virulence by quorum ...
We show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing.
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Overcoming Bacterial Drug Resistance with Quorum Sensing ...
Apr 28, 2025 · In this study, we aimed to find the synergistic combinations between the QSIs and known antibiotics to combat the two deadliest hospital infections.
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An insight on the powerful of bacterial quorum sensing inhibition
Aug 19, 2024 · Recent research indicates that quorum sensing inhibitors (QSIs) and quorum quenching enzymes (QQEs) show great promise in reducing the pathogenicity of ...Missing: anaerobic | Show results with:anaerobic<|separator|>
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Combatting biofilms in potable water systems - NIH
Oct 12, 2023 · Quorum sensing, a microbial signalling mechanism, enables these communities to gauge their population density and orchestrate collective ...
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Quorum sensing regulation methods and their effects on biofilm in ...
Nov 2, 2021 · This review summarizes the methods of QS enhancement and QS inhibition in biological waste treatment systems.
[128]
Engineering quorum sensing-based genetic circuits enhances ... - NIH
Sep 28, 2024 · This study demonstrates an effective strategy to enhance the acid tolerance and productivity of an industrial E. coli strain in scaled-up ...
[129]
Combination of enzyme engineering and quorum sensing system for ...
Aug 22, 2025 · Application of an optimized fed-batch fermentation increased the final accumulation of β-arbutin to 81.9 g/L, with a productivity of 1.36 g/L/h.
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Innovative microbial disease biocontrol strategies mediated by ...
Based on the quorum sensing mechanism, quorum quenching has been promoted as an efficient biological control strategy, with a promising future in agricultural, ...
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Role of Quorum Sensing Molecules in Plant-Microbe Interaction for ...
May 21, 2025 · The paper discusses the role of QS in enhancing plant growth-promoting rhizobacteria (PGPR), nitrogen-fixing and phosphate-solubilising bacteria ...
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Quorum Sensing Inhibition by Sponge-Associated Bacillus Species
Given the complexity of the sponge holobiont, sponge-associated microorganisms may demonstrate QS inhibitory properties and serve as potential sources of novel ...
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Regulation of anti-phage defense mechanisms by using ... - Frontiers
Many bacteria regulate the expression of defense mechanisms against phages by quorum sensing (QS) (Høyland-Kroghsbo et al., 2017; Rémy et al., 2018). QS is ...Abstract · Introduction · Results · Discussion
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Resistance to quorum sensing inhibition spreads more slowly during ...
Mar 11, 2025 · It was recently shown that resistance to quorum sensing inhibition will spread more slowly during infection of a host than resistance to traditional ...
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Challenges and Limitations of Anti-quorum Sensing Therapies
One of the main assumptions of anti-QS therapy is the reduction of pathogens' virulence by limiting the communication-dependent pathogenicity induction, ...
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PqsR-specific quorum sensing inhibitors targeting Pseudomonas ...
Despite their potential, several challenges remain in the clinical application of PqsR inhibitors. Issues such as optimizing drug delivery, ensuring ...
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Tools for engineering coordinated system behaviour in synthetic ...
Jul 11, 2018 · The most frequently used quorum-sensing parts, the LuxR protein and its cognate Plux promoter have been assembled into a AHL-receiver device ...Missing: seminal | Show results with:seminal
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Quantifying the optimal strategy of population control of quorum ...
Sep 2, 2021 · Here, we construct a comprehensive mathematical model of the synthetic quorum sensing circuit that controls population density in Escherichia coli.Missing: seminal | Show results with:seminal
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Characterization and orthogonality assessment of two quorum ...
Apr 3, 2025 · This research characterized LasI/LasR and EsaI/EsaR quorum sensing systems, assessed their orthogonality, and found low promoter crosstalk, ...
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Engineered Orthogonal Quorum Sensing Systems for Synthetic ...
We report an investigation of quorum sensing components to identify synthetic pathways that exhibit little to no crosstalk in liquid and solid cultures.
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Multi-Faceted Characterization of a Novel LuxR-Repressible ...
May 26, 2015 · The genetic elements regulating the natural quorum sensing (QS) networks of several microorganisms are widely used in synthetic biology to ...
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Designer cells programming quorum-sensing interference with ...
May 8, 2018 · Quorum sensing is a promising target for next-generation anti-infectives designed to address evolving bacterial drug resistance.
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An Engineered Probiotic Consortium Based on Quorum‐Sensing for ...
Sep 26, 2025 · This work develops an engineered probiotic consortium sensing pH, hypoxia, and lactate in the tumor microenvironment.
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Quorum-Sensing Synchronization of Synthetic Toggle Switches - NIH
Among all engineered synthetic circuits, a toggle, a robust bistable switch leading to a binary response dynamics, is the simplest basic synthetic biology ...Missing: gates | Show results with:gates
[145]
Expanding the quorum sensing toolbox: Promoter libraries and ...
Sep 12, 2025 · The interesting features of quorum sensing systems make them very appealing for synthetic biology applications. The first steps have already ...
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Quorum Sensing: Not Just a Bridge Between Bacteria - Liu - 2025
Mar 30, 2025 · Advancements in QS regulation, such as the use of nanomaterials, hydrogels, and microplastics, provide novel methods to modulate QS systems.
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Innovative applications of multidimensional engineered hydrogels in ...
Aug 6, 2025 · By synergizing advances in synthetic biology, nanotechnology, and AI-driven design, next-generation hydrogels may pioneer a new era of precision ...
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When less is more: Robot swarms adapt better to changes ... - Science
Jul 21, 2021 · The Kilobot swarm adapts to environmental changes when robots use short-range communication. Results from 100 simulations (A to D) and six ...
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Reducing planning time in swarm exploration via quorum sensing ...
Oct 2, 2025 · Robots emit and sense a diffusive field using two scalar probes and a contact signal, select one of four motion primitives from local gradients, ...
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https://www.science.org/doi/10.1126/scirobotics.abf1416
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Quorum Sensing in Emulsion Droplet Swarms Driven by a ...
Jun 17, 2024 · Quorum sensing is established in emulsion droplet swarms that float at a water surface and cluster above a critical density.
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https://www.researchgate.net/publication/396000686_Reducing_planning_time_in_swarm_exploration_via_quorum_sensing_and_discrete-event_scheduling
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Programmable Bacterial Biofilms as Engineered Living Materials
Jun 15, 2024 · Self-organizing living materials are created by genetically altering biofilm components, giving rise to new functions while maintaining the ...
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The 2025 motile active matter roadmap - PMC - PubMed Central - NIH
By detecting chemical signals emitted by other cells, bacteria can regulate gene expression in response to cell population density. Exploiting the quorum ...
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Reclassification of Vibrio fischeri, Vibrio logei, Vibrio salmonicida and Vibrio wodanis as Aliivibrio fischeri gen. nov., comb. nov., Aliivibrio logei comb. nov., Aliivibrio salmonicida comb. nov. and Aliivibrio wodanis comb. nov.
This peer-reviewed paper proposes the reclassification of Vibrio fischeri to the genus Aliivibrio based on phylogenetic and phenotypic analyses, published in the International Journal of Systematic and Evolutionary Microbiology in 2007.