The quorum sensing SinI/R system contributes to cadmium immobilization in Ensifer adhaerens NER9 in the cadmium-contaminated solution.

In this study, the cadmium (Cd)-tolerant Ensifer adhaerens strain NER9 with quorum sensing (QS) systems (responsible for N-acyl homoserine lactone (AHL) production) was characterized for QS system-mediated Cd immobilization and the underlying mechanisms involved. Whole-genome sequence analysis revealed that strain NER9 contains the QS SinI/R and TraI/R systems. Strains NER9 and the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants were constructed and compared for QS SinI/R and TraI/R system-mediated Cd immobilization in the solution and the mechanisms involved. After 24 h of incubation, strain NER9 significantly decreased the Cd concentration in the Cd-contaminated solution compared with the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants. The NER9∆sinI/R mutant had a greater impact on Cd immobilization and a lower impact on the activities of AHLs than did the NER9∆traI/R mutant. The NER9∆sinI/R mutant had significantly greater Cd concentrations and lower cell wall- and exopolysaccharide (EPS)-adsorbed Cd contents than did strain NER9. Furthermore, the NER9∆sinI/R mutant presented a decrease in the number of functional groups interacting with Cd, compared with strain NER9. These results suggested that the SinI/R system in strain NER9 contributed to Cd immobilization by mediating cell wall- and EPS-adsorption in Cd-containing solution.

Abiotic Small Molecule Inhibitors and Activators of the LasR Quorum Sensing Receptor in Pseudomonas aeruginosa with Potencies Comparable or Surpassing N-Acyl Homoserine Lactones.

The opportunistic pathogen Pseudomonas aeruginosa controls almost 10% of its genome, including myriad virulence genes, via a cell-to-cell chemical communication system called quorum sensing (QS). Small molecules that either inhibit or activate QS in P. aeruginosa represent useful research tools to study the role of this signaling pathway in infection and interrogate its viability as an antivirulence target. However, despite active research in this area over the past 20+ years, there are relatively few synthetic compounds known to strongly inhibit or activate QS in P. aeruginosa. Most reported QS modulators in this pathogen are of low potency or have structural liabilities that limit their application in biologically relevant environments such as mimics of the native N-acyl l-homoserine lactone (AHL) signals. Here, we report the results of a high-throughput screen for abiotic small molecules that target LasR, a key QS regulator in P. aeruginosa. We screened a 25,000-compound library and discovered four new structural classes of abiotic LasR modulators. These compounds include antagonists that surpass the potency of all known AHL-type compounds and mimetics thereof, along with an agonist with potency approaching that of LasR's native ligand. The novel structures of this compound set, along with their anticipated robust physicochemical profiles, underscore their potential value as probe molecules to interrogate the roles of QS in this formidable pathogen.

Engineering quorum quenching acylases with improved kinetic and biochemical properties.

Many Gram-negative bacteria use N-acyl-L-homoserine lactone (AHL) signals to coordinate phenotypes such as biofilm formation and virulence factor production. Quorum-quenching enzymes, such as AHL acylases, chemically degrade these molecules which prevents signal reception by bacteria and inhibits undesirable biofilm-related traits. These capabilities make acylases appealing candidates for controlling microbes, yet candidates with high activity levels and substrate specificity and that are capable of being formulated into materials are needed. In this work, we undertook engineering efforts against two AHL acylases, PvdQ and MacQ, to generate these improved properties using the Protein One-Stop Shop Server. The engineering of acylases is complicated by low-throughput enzymatic assays. Alleviating this challenge, we report a time-course kinetic assay for AHL acylases that monitors the real-time production of homoserine lactone. Using the assay, we identified variants of PvdQ that were significantly stabilized, with melting point increases of up to 13.2°C, which translated into high resistance against organic solvents and increased compatibility with material coatings. While the MacQ mutants were unexpectedly destabilized, they had considerably improved kinetic properties, with >10-fold increases against N-butyryl-L-homoserine lactone and N-hexanoyl-L-homoserine lactone. Accordingly, these changes resulted in increased quenching abilities using a biosensor model and greater inhibition of virulence factor production of Pseudomonas aeruginosa PA14. While the crystal structure of one of the MacQ variants, M1, did not reveal obvious structural determinants explaining the observed changes in kinetics, it allowed for the capture of an acyl-enzyme intermediate that confirms a previously hypothesized catalytic mechanism of AHL acylases.

Comprehensive Similarity Algorithm and Molecular Dynamics Simulation-Assisted Terahertz Spectroscopy for Intelligent Matching Identification of Quorum Signal Molecules (N-Acyl-Homoserine Lactones).

To investigate the mechanism of aquatic pathogens in quorum sensing (QS) and decode the signal transmission of aquatic Gram-negative pathogens, this paper proposes a novel method for the intelligent matching identification of eight quorum signaling molecules (N-acyl-homoserine lactones, AHLs) with similar molecular structures, using terahertz (THz) spectroscopy combined with molecular dynamics simulation and spectral similarity calculation. The THz fingerprint absorption spectral peaks of the eight AHLs were identified, attributed, and resolved using the density functional theory (DFT) for molecular dynamics simulation. To reduce the computational complexity of matching recognition, spectra with high peak matching values with the target were preliminarily selected, based on the peak position features of AHL samples. A comprehensive similarity calculation (CSC) method using a weighted improved Jaccard similarity algorithm (IJS) and discrete Fréchet distance algorithm (DFD) is proposed to calculate the similarity between the selected spectra and the targets, as well as to return the matching result with the highest accuracy. The results show that all AHL molecular types can be correctly identified, and the average quantization accuracy of CSC is 98.48%. This study provides a theoretical and data-supported foundation for the identification of AHLs, based on THz spectroscopy, and offers a new method for the high-throughput and automatic identification of AHLs.

Potential role of quorum quenching activity of silver nanoparticles in controlling non-filamentous bulking within activated sludge process.

The effective prevention and control of non-filamentous bulking is a significant challenge. In this study, the underlying effect of quorum sensing (QS) on inducing non-filamentous bulking and the maintenance effect of silver nanoparticles (AgNPs) on sludge floc stability, aggregation and settleability based on the quorum quenching (QQ) activity during non-filamentous bulking were investigated. The results showed that the concentration of N-acyl homoserine lactone (AHL) increased significantly in the activated sludge system at a high organic load rate (OLR), triggering the AHL-mediated QS. Additionally, the triggered QS promoted exopolysaccharide secretion, reducing the surface charge and hydrophobicity of the sludge aggregates, and further deteriorating the settleability of the sludge aggregates. AgNPs, a quorum sensing inhibitor (QSI), inhibited the AHL-QS based on QQ activity under high OLR, which maintained the physicochemical properties of extracellular polymeric substances (EPS). AgNPs-QQ maintained the surface energy barrier and electrostatic barrier of sludge aggregates and the gel properties of exopolysaccharides, which is favorable for microbial aggregation. The appropriate concentrations of AgNPs (≤10 mg/L) had no negative effect on biological nutrient removal in the sequencing batch reactors (SBRs) at the high organic loading. Therefore, AgNPs effectively prevent and control non-filamentous bulking by their QQ activity in the activated sludge process. Thus, the present study provided new insights into controlling non-filamentous bulking during the activated sludge process.

Bromination of Quorum Sensing Molecules: Vanadium Bromoperoxidase and Cerium Dioxide Nanocrystals via Free Active Bromine Transform Bacterial Communication.

The halogenation of quorum sensing molecules (QSMs) is known to be catalyzed by enzymes such as haloperoxidase (HPO) as well as cerium dioxide nanocrystals (NC), which mimic enzymes. Those enzymes and mimics can influence biological processes such as biofilm formation, where bacteria use QSMs for the "chemical" communication between each other and the coordination of surface colonization. However, not much is known about the degradation behavior of a broad spectrum of QSMs, especially for HPO and its mimics. Therefore, in this study, the degradation of three QSMs with different molecule moieties was elucidated. For this purpose, different batch experiments were carried out with HPOs, NCs and free active bromine (FAB). For N-ß-ketocaproyl-homoserine lactone (3-Oxo-C6-AHL), N-cis-tetradec-9Z-enoyl-homoserine lactone (C14:1-AHL) and 2-heptyl-4-quinolone (HHQ) a fast degradation and moiety-specific transformations were observed. The HPO vanadium bromoperoxidase as well as cerium dioxide NCs catalyzed the formation of the same brominated transformation products (TPs). Since the same TPs are formed in batch experiments with FAB it is very likely that FAB is playing a major role in the catalytical reaction mechanism leading to the transformation of QSMs. In this study in total 17 TPs could be identified in different levels of confidence and the catalytic degradation processes for two QS groups (unsaturated AHLs and alkyl quinolones) with cerium dioxide NCs and vanadium bromoperoxidase were expanded.

Carrier protein mediated cargo sensing in quorum signal synthases.

Acyl-homoserine lactone synthases make specific AHL quorum sensing signals to aid virulence in Gram-negative bacteria. Here, we use solution NMR spectroscopy to demonstrate that the carrier protein-enzyme interface accurately reveals substrate recognition mechanisms in two quorum signal synthases.

Exploring the Function of Quorum Sensing Regulated Biofilms in Biological Wastewater Treatment: A Review.

Quorum sensing (QS), a type of bacterial cell-cell communication, produces autoinducers which help in biofilm formation in response to cell population density. In this review, biofilm formation, the role of QS in biofilm formation and development with reference to biological wastewater treatment are discussed. Autoinducers, for example, acyl-homoserine lactones (AHLs), auto-inducing oligo-peptides (AIPs) and autoinducer 2, present in both Gram-negative and Gram-positive bacteria, with their mechanism, are also explained. Over the years, wastewater treatment (WWT) by QS-regulated biofilms and their optimization for WWT have gained much attention. This article gives a comprehensive review of QS regulation methods, QS enrichment methods and QS inhibition methods in biological waste treatment systems. Typical QS enrichment methods comprise adding QS molecules, adding QS accelerants and cultivating QS bacteria, while typical QS inhibition methods consist of additions of quorum quenching (QQ) bacteria, QS-degrading enzymes, QS-degrading oxidants, and QS inhibitors. Potential applications of QS regulated biofilms for WWT have also been summarized. At last, the knowledge gaps present in current researches are analyzed, and future study requirements are proposed.

Communication Breakdown: Into the Molecular Mechanism of Biofilm Inhibition by CeO2 Nanocrystal Enzyme Mimics and How It Can Be Exploited.

Bacterial biofilm formation is a huge problem in industry and medicine. Therefore, the discovery of anti-biofilm agents may hold great promise. Biofilm formation is usually a consequence of bacterial cell-cell communication, a process called quorum sensing (QS). CeO2 nanocrystals (NCs) have been established as haloperoxidase (HPO) mimics and ecologically beneficial biofilm inhibitors. They were suggested to interfere with QS, a mechanism termed quorum quenching (QQ), but their molecular mechanism remained elusive. We show that CeO2 NCs are effective QQ agents, inactivating QS signals by bromination. Catalytic bromination of 3-oxo-C12-AHL a QS signaling compound used by Pseudomonas aeruginosa, was detected in the presence of CeO2 NCs, bromide ions, and hydrogen peroxide. Brominated acyl-homoserine lactones (AHLs) no longer act as QS signals but were not detected in the bacterial cultures. Externally added brominated AHLs also disappeared in P. aeruginosa cultures within minutes of their addition, indicating that they are rapidly degraded by the bacteria. Moreover, we detected the catalytic bromination of 2-heptyl-1-hydroxyquinolin-4(1H)-one (HQNO), a multifunctional non-AHL QS signal from P. aeruginosa with antibacterial and algicidal properties controlling the expression of many virulence genes. Brominated HQNO was not degraded by the bacteria in vivo. The repression of the Pseudomonas quinolone signal (PQS) production and biofilm formation in P. aeruginosa through the catalytic formation of Br-HQNO on surfaces with coatings containing CeO2 enzyme mimics validates the non-toxic strategy for the development of anti-infectives.

Furanone and phytol influence metabolic phenotypes regulated by acyl-homoserine lactone in Salmonella.

Salmonella is an important foodborne pathogen, and it is unable to produce the quorum sensing signaling molecules called acyl-homoserine lactones (AHLs). However, it synthesizes the SdiA protein, detecting AHL molecules, also known as autoinducer-1 (AI-1), in the external environment. Exogenous AHLs can regulate specific genes related to virulence and stress response in Salmonella. Thus, interfering with quorum sensing can be a strategy to reduce virulence and help elucidate the cell-to-cell communication role in the pathogens' response to extracellular signals. This study aimed to evaluate the influence of the quorum sensing inhibitors furanone and phytol on phenotypes regulated by N-dodecanoyl homoserine lactone (C12-HSL) in Salmonella enterica serovar Enteritidis. The furanone C30 at 50 nM and phytol at 2 mM canceled the alterations promoted by C12-HSL on glucose consumption and the levels of free cellular thiol in Salmonella Enteritidis PT4 578 under anaerobic conditions. In silico analysis suggests that these compounds can bind to the SdiA protein of Salmonella Enteritidis and accommodate in the AHL binding pocket. Thus, furanone C30 and phytol act as antagonists of AI-1 and are likely inhibitors of the quorum sensing mechanism mediated by AHL in Salmonella.

Autoinducer-fluorophore conjugates enable FRET in LuxR proteins in vitro and in cells.

Cell-to-cell signaling, or quorum sensing (QS), in many Gram-negative bacteria is governed by small molecule signals (N-acyl-L-homoserine lactones, AHLs) and their cognate receptors (LuxR-type proteins). The mechanistic underpinnings of QS in these bacteria are severely limited due to the challenges of isolating and manipulating most LuxR-type proteins. Reports of quantitative direct-binding experiments on LuxR-type proteins are scarce, and robust and generalizable methods that provide such data are largely nonexistent. We report herein a Förster resonance energy transfer (FRET) assay that leverages (1) conserved tryptophans located in the LuxR-type protein ligand-binding site and synthetic fluorophore-AHL conjugates, and (2) isolation of the proteins bound to weak agonists. The FRET assay permits straightforward measurement of ligand-binding affinities with receptor-either in vitro or in cells-and was shown to be compatible with six LuxR-type proteins. These methods will advance fundamental investigations of LuxR-type protein mechanism and the development of small molecule QS modulators.

Applying molecular and phenotypic screening assays to identify efficient quorum quenching lactonases.

Quorum sensing (QS) is a molecular communication system used by microorganisms to adopt behaviors in a cell density-dependent manner. Lactonase enzymes, able to hydrolyze the signal molecules acyl-homoserine lactones (AHL) can counteract QS-mediated virulence in Gram-negative bacteria. Optimizing lactonases activity or specificity for AHL through enzyme engineering approaches is thus highly attractive to increase protective effect. However, only a limited number of screening methods have been developed to handle and evaluate AHL-degrading enzyme libraries. Here, a series of screening procedures were developed to identify improved lactonases using two previously reported enzymes as benchmarks, namely SsoPox and GcL. Specifically, molecular screenings using six different AHL and based on two reporter strains; i.e., Chromobacterium violaceum CV026 and Pseudomonas putida KS35, are reported. In addition, three phenotype-based screenings aiming to evaluate the ability of enzymes to quench a particular QS-related behavior are reported, using C. violaceum, Pseudomonas aeruginosa and Vibrio harveyi as pathogenic type strains. These assays were used to screen a small-sized library and allowed for the identification of various improved variants. To confirm that these variants were real "hits", four of them were produced and purified. Their kinetic parameters against AHL substrates were found to be increased by 2-44.5 -fold as compared to the starting enzyme. Moreover, their increased activity was confirmed by measuring their ability to quench QS in different bacterial systems. These new assays will facilitate the screening of enzyme libraries and will pave the way for the development of proficient engineered QS-disrupting enzymes.

Making Sense of Quorum Sensing at the Intestinal Mucosal Interface.

The gut microbiome can produce metabolic products that exert diverse activities, including effects on the host. Short chain fatty acids and amino acid derivatives have been the focus of many studies, but given the high microbial density in the gastrointestinal tract, other bacterial products such as those released as part of quorum sensing are likely to play an important role for health and disease. In this review, we provide of an overview on quorum sensing (QS) in the gastrointestinal tract and summarise what is known regarding the role of QS molecules such as auto-inducing peptides (AIP) and acyl-homoserine lactones (AHL) from commensal, probiotic, and pathogenic bacteria in intestinal health and disease. QS regulates the expression of numerous genes including biofilm formation, bacteriocin and toxin secretion, and metabolism. QS has also been shown to play an important role in the bacteria-host interaction. We conclude that the mechanisms of action of QS at the intestinal neuro-immune interface need to be further investigated.

Insights into Adaptive Mechanisms of Extreme Acidophiles Based on Quorum Sensing/Quenching-Related Proteins.

Quorum sensing (QS) is a unique mechanism for microorganisms to coordinate their activities through intercellular communication, including four main types of autoinducer-1 (AI-1, namely, N-acyl homoserine lactone [AHL]), AI-2, AI-3, and diffusible signaling factor [DSF]) based on signaling molecules. Quorum quenching (QQ) enzymes can disrupt the QS phenomenon by inactivating signaling molecules. QS is proposed to regulate biofilm formation in extremely acidic environments, but the QS/QQ-related genomic features in most acidophilic bacteria are still largely unknown. Here, genome annotation of 83 acidophiles from the genera Acidithiobacillus, Leptospirillum, Sulfobacillus, and Acidiphilium altogether revealed the existence of AI-1, AI-3, DSF, and AhlD (AHL degradation enzyme). The conservative investigation indicated that some QS/QQ-related proteins harbored key residues or motifs, which were necessary for their activities. Phylogenetic analysis showed that LuxI/R (AI-1 synthase/receptor), QseE/F (two-component system of AI-3), and RpfC/G (two-component system of DSF) exhibited similar evolutionary patterns within each pair. Meanwhile, proteins clustered approximately according to the species taxonomy. The widespread Acidithiobacillus strains, especially A. ferrooxidans, processed AI-1, AI-3, and DSF systems as well as the AhlD enzyme, which were favorable for their mutual information exchange and collective regulation of gene expression. Some members of the Sulfobacillus and Acidiphilium without AHL production capacity contained the AhlD enzyme, which may evolve for niche competition, while DSF in Leptospirillum and Acidithiobacillus could potentially combine with the cyclic diguanylate (c-di-GMP) pathway for self-defense and niche protection. This work will shed light on our understanding of the extent of communication networks and adaptive evolution among acidophiles via QS/QQ coping with environmental changes. IMPORTANCE Understanding cell-cell communication QS is highly relevant for comprehending the regulatory and adaptive mechanisms among acidophiles in extremely acidic ecosystems. Previous studies focused on the existence and functionality of a single QS system in several acidophilic strains. Four representative genera were selected to decipher the distribution and role of QS and QQ integrated with the conservative and evolutionary analysis of related proteins. It was implicated that intra- or intersignaling circuits may work effectively based on different QS types to modulate biofilm formation and energy metabolism among acidophilic microbes. Some individuals could synthesize QQ enzymes for specific QS molecular inactivation to inhibit undesirable acidophile species. This study expanded our knowledge of the fundamental cognition and biological roles underlying the dynamical communication interactions among the coevolving acidophiles and provided a novel perspective for revealing their environmental adaptability.

Straightforward N-Acyl Homoserine Lactone Discovery and Annotation by LC-MS/MS-based Molecular Networking.

N-Acyl-l-homoserine lactones (AHLs) are a large family of signaling molecules in "quorum sensing" communication. This mechanism is present in a number of bacterial physiological phenomena, including pathogenic phenomena. In this study, we described a simple and accessible way to detect, annotate, and quantify these compounds from bacterial culture media. Analytical standards and ethyl acetate bacterial extracts containing AHLs were analyzed by an ultra-high-performance liquid chromatography system coupled to a mass spectrometer using a nontargeted FullMS data-dependent MS2 method. The results were processed in MZmine2 and then analyzed by a Feature-Based Molecular Networking (FBMN) workflow in the Global Natural Products Social Networking (GNPS) platform for the discovery and annotation of known and unknown AHLs. Our group analyzed 31 AHL standards and included the MS2 spectra in the spectral library of the GNPS platform. We also provide the 31 standard AHL spectrum list for inclusion in molecular networking analyses. FBMN analysis annotated 30 out of 31 standards correctly. Then, as an example, a set of five bacterial extracts was prepared for AHL annotation. Following the method described in this Article, 5 known and 11 unknown AHLs were properly annotated using the FBMN-based molecular network approach. This study offers the possibility for the automatic annotation of known AHLs and the search for nonreferenced AHLs in bacterial extracts in a somewhat straightforward approach even without acquiring analytical standards. The method also provides relative quantification information.

Combined Modification of Fiber Materials by Enzymes and Metal Nanoparticles for Chemical and Biological Protection.

To obtain fiber materials with pronounced chemical-biological protection, metal (Zn or Ta) nanoparticles were jointly applied with polyelectrolyte complexes of enzymes and polypeptides being their stabilizers. Computer modeling revealed the preferences between certain polyelectrolyte partners for N-acyl-homoserine lactone acylase and hexahistidine-tagged organophosphorus hydrolase (His6-OPH) possessing the quorum quenching (QQ) behavior with bacterial cells. The combinations of metal nanoparticles and enzymes appeared to function better as compared to the combinations of the same QQ-enzymes with antibiotics (polymyxins), making it possible to decrease the applied quantities by orders of magnitude while giving the same effect. The elimination of Gram-positive and Gram-negative bacterial cells from doubly modified fiber materials notably increased (up to 2.9-fold), whereas His6-OPH retained its hydrolytic activity in reaction with organophosphorus compounds (up to 74% of initially applied activity). Materials with the certain enzyme and Zn nanoparticles were more efficient against Bacillus subtilis cells (up to 2.1-fold), and Ta nanoparticles acted preferentially against Escherichia coli (up to 1.5-fold). Some materials were proved to be more suitable for combined modification by metal nanoparticles and His6-OPH complexes as antimicrobial protectants.

N-acyl-homoserine lactone produced by Rahnella inusitata isolated from the gut of Galleria mellonella influences Salmonella phenotypes.

The most studied mechanism of quorum sensing in Gram-negative bacteria is mediated by autoinducer 1 (AI-1), namely, acyl-homoserine lactone (AHL). This system allows communication among different bacterial species and regulates the expression of virulence genes in many pathogens. Although AHL-producing bacteria have been detected in the intestines of humans and other animals, no report was found about AHL-producing bacteria in the insect gut and the possible effects of these autoinducers on enteropathogenic bacteria. Therefore, this study aimed to identify AHL-producing bacteria in the gut of larvae of Galleria mellonella and to evaluate the influence of this quorum sensing signal on the regulation of adhesion and motility phenotypes in the intestinal pathogen Salmonella. Sequencing of the 16S rRNA gene, 16S rRNA gene-based phylogenetic analyses, and phenotypic characterization of gut isolates was performed. The profile of AHLs produced by the isolates was determined using thin-layer chromatography (TLC) and revealed with the biosensor strain Chromobacterium violaceum CV026. Sequencing, phylogenetic analyses and phenotypic characterization of gut isolates showed that the three AHL-producing strains belong to the species Rahnella inusitata, named GM34, GM56, and GM60. The TLC showed that R. inusitata produces a six-carbon AHL. In the presence of cell-free extract of R. inusitata containing AHL and under anaerobic conditions, Salmonella enterica increased the adhesion to stainless steel coupons and presented swarming motility. Extracts from the culture medium of R. inusitata isolates containing AHL increased the adhesion on stainless steel coupons and swarming motility of Salmonella enterica serovar Enteritidis PT4 under anaerobic conditions. The results suggest the possibility of communication between members of the G. mellonella intestinal microbiota with pathogens such as Salmonella.

Human TRPV1 and TRPA1 are receptors for bacterial quorum sensing molecules.

In this study, we investigated the activation of TRPV1 and TRPA1 by N-acyl homoserine lactones, quorum sensing molecules produced by Gram-negative bacteria, and the inhibitory effect of TRPV1 and TRPA1 by autoinducing peptides (AIPs), quorum sensing molecules produced by Gram-positive bacteria, using human embryonic kidney 293T cell lines stably expressing human TRPV1 and TRPA1, respectively. As a result, we found that some N-acyl homoserine lactones, such as N-octanoyl-L-homoserine lactone (C8-HSL), N-nonanoyl-L-homoserine lactone (C9-HSL) and N-decanoyl-L-homoserine lactone (C10-HSL), activated both TRPV1 and TRPA1. In addition, we clarified that some N-acyl homoserine lactones, such as N-3-oxo-dodecanoyl-L-homoserine lactone (3-oxo-C12-HSL), only activated TRPV1 and N-acyl homoserine lactones having saturated short acyl chain, such as N-acetyl-L-homoserine lactone (C2-HSL) and N-butyryl-L-homoserine lactone (C4-HSL), only activated TRPA1. Furthermore, we found that an AIP, simple linear peptide CHWPR, inhibited both TRPV1 and TRPA1 and peptide having thiolactone ring DICNAYF, the thiolactone ring were formed between C3 to F7, strongly inhibited only the TRPV1. Although the specificity of TRPV1 and TRPA1 for quorum sensing molecules was different, these data suggest that both TRPV1 and TRPA1 would function as receptors for quorum sensing molecule produced by bacteria. Graphical Abstract.

Quorum Sensing Inhibitory Potential and Molecular Docking Studies of Phyllanthus emblica Phytochemicals Against Pseudomonas aeruginosa.

Phyllanthus emblica is a traditional medicinal plant that is endowed with curative properties including anti-bacterial, anti-fungal, anti-viral, and analgesic properties. Bacteria make use of cell-cell signaling system known as quorum sensing (QS) and respond to their own population. In most gram-negative bacteria, the transcriptional regulators belonging to the Lux R protein play a crucial role in the QS mechanism by detecting the presence of signaling molecules known as N-acyl homoserine lactones (AHLs). In this present work, the anti-quorum sensing activity of Phyllanthus emblica was evaluated against Pseudomonas aeruginosa. Anti-quorum sensing efficacy of Phyllanthus emblica was estimated with reference to QS bio-monitoring strain Chromobacterium violaceum. The binding efficacy of the phytochemicals of Phyllanthus emblica against CviR protein from Chromobacterium violaceum and LasR protein from Phyllanthus emblica were studied.

Chemical probe of AHL modulators on quorum sensing in Gram-Negative Bacteria and as antiproliferative agents: A review.

Pathogenic bacteria use an intercellular chemical communication system called quorum sensing (QS) to control the expression of cellular functions such as virulence factors, biofilm formation, toxin production, and antibiotic resistance in a manner that is highly dependent on population density. Hence, since the emergence of QS, there has been a great interest in exploiting the QS mechanism as a new drug target. Therefore, blocking the QS mechanism can be an effective strategy to control infection and solve the problem of drug resistance. So far, there is no clinically approved anti-QS drug that can disable the circuits of QS systems. This review discusses the quorum-sensing network systems and novel anti-QS inhibitors in some Gram-negative bacteria.