Quorum-sensing Signal Research Articles

In Situ Enrichment of Anammox Bacteria from Pig Farm Anoxic Sludge Through Co-Cultivation with a Quorum-Sensing Functional Strain Pseudomonas aeruginosa

Anaerobic ammonium oxidation (anammox), as an efficient and low-carbon method for nitrogen removal from wastewater, faces the challenge of slow enrichment of functional bacteria. In this study, the enrichment of anammox bacteria Candidatus Brocadia was successfully accelerated by co-culturing with the quorum-sensing strain Pseudomonas aeruginosa and anoxic sludge from a pig farm. Experimental results showed that the R2, which had Pseudomonas aeruginosa added, exhibited chemical reaction ratios RS (NO2−-N consumption/NH4+-N consumption) and RP (NO3−-N production/NH4+-N consumption) closer to the theoretical values of the anammox reaction since Phase Ⅱ. Bacterial community analysis indicated that the abundance of Candidatus Brocadia in R2 reached 1.63% in cycle 20, significantly higher than the 0.45% in R1. More quorum-sensing signaling molecules, primarily C6-HSL, were detected in R2. C6-HSL was positively correlated with processes such as the secretion of anammox extracellular polymers (EPS) and the regulation of nitric oxide reductase (Nir), which may explain the reason behind the accelerated increase in the abundance of Candidatus Brocadia through co-culturing. Moreover, the metabolism of the dominant genus Paracoccus within the two groups of reactors also showed positive regulation by C6-HSL, with its abundance trend similar to that of Candidatus Brocadia, jointly completing the nitrogen removal process in the reactors. However, it is still unknown which genera secrete large amounts of C6-HSL after inoculation with Pseudomonas aeruginosa. This research provides a novel and low-cost method for the enrichment of anammox bacteria.

Identification and Validation of Garlic (Allium sativum) Metabolites as Quorum Sensing Inhibitors of Bacillus cereus Targeting the PlcR Receptor: An In Silico and In Vitro Study.

This study aimed to investigate the influence of garlic metabolites on the quorum sensing (QS) of Bacillus cereus, a foodborne pathogen that controls its main virulence factor through QS. The QS signal receptor PlcR of B. cereus was targeted by molecular docking with 82 garlic metabolites to identify the most potent QS inhibitors. Five metabolites, quercetin, kaempferol, luteolin, flavone, and rutin, were selected for further evaluation of their impacts on the growth, toxin production, and virulence of B. cereus in vitro. The expression levels of key QS genes were also measured to verify their anti-QS ability. The results revealed that quercetin reduced enterotoxin production by B. cereus but did not affect the QS process at the transcriptional level; flavone and rutin in garlic interfered with the QS of B. cereus by competing with the autoinducing peptide (AIP) PapR7 for the PlcR binding site, resulting in decreased enterotoxin secretion and hemolysis without altering the bacterial growth. Interestingly, luteolin and kaempferol in garlic acted as AIP analogs and bound to PlcR to stimulate the QS process and virulence. Furthermore, kaempferol, luteolin, flavone, and rutin had distinct or opposite interactions with PapR7 at the Gln237 or Tyr275 residues of PlcR, which determined the suppression or enhancement of the QS process. The findings suggested that flavone and rutin were effective compounds to inhibit the QS process in garlic and could be used as alternative methods to control B. cereus.

Metabolic complexities and heterogeneity in quorum sensing signaling molecules in bacteria isolated from black band disease in a Caribbean coral

Coral diseases contribute to the worldwide loss of coral reefs, with the Black Band Disease (BBD) being a prominent example. BBD is an infectious condition with lesions with a pigmented mat composed of cyanobacteria, sulphate-reducing, sulphide-oxidizing, and heterotrophic bacteria. We compared the heterotrophic bacterial communities of healthy and BBD-affected colonies of the Caribbean coral Orbicella faveolata using culture-dependent and -independent techniques. Twenty and 23 bacterial isolates were identified from healthy and diseased tissues, respectively, which differed in their capacities to metabolize carbohydrates and citrate, either anaerobically or aerobically. They also differed in their quorum-sensing (QS) activity, as QS signaling molecules were found exclusively, and QS-inhibition was found primarily, in isolates from diseased tissues. Screening of bacterial diversity by 16SrDNA metabarcoding showed that members of the bacterial genera Muricauda and Maritimimonas were dominant in healthy tissues whereas members of the cyanobacterial genus Roseofilum were dominant in diseased tissues. These results suggest that bacterial dysbiosis can be linked with altered bacterial communication, likely leading to diachrony and imbalance that may participate in the progression of BBD. Investigating physiological traits and QS-based communication offers insights into the onset and progression of coral infections, paving the way for novel strategies to mitigate their impact.

Design, Synthesis, Biological Evaluation, and In Silico Study of N‐(Pyridin‐2/3‐yl)alkanamide Derivatives as Quorum Sensing Inhibitors Against Pseudomonas aeruginosa

AbstractThe effectiveness of treating bacterial infections is seriously jeopardized by the emergence of bacterial resistance to chemical therapy. The development of biofilm in bacteria is one of the main causes of resistance to antimicrobial drugs. By developing new antibiofilm medications, quorum sensing (QS) inhibitor was developed as an alternate therapy. QS inhibition, which focuses on the QS signaling pathway, obstructs cell–cell communication. The aim of this work is to develop newer QS inhibitors against Pseudomonas aeruginosa. N‐(Pyridin‐2/3‐yl)alkanamide derivatives were designed as QS inhibitors, and these designed molecules were synthesized. QS inhibitor activity was evaluated for the synthesized compounds (3a–l, 4a–h). The highest QS inhibitor activities for compounds 3k, 4a, and 4c were 11.66 ± 0.11, 14.66 ± 0.15, and 10.66 ± 0.05 mm, respectively. Subsequent molecular docking analyses exhibited moderate to good binding affinity values between −7.1 and −9.3 kcal/mol. Using the in silico method, the physicochemical characteristics of these prepared compounds were examined. Additionally, molecular dynamic simulation was employed to gain a deeper comprehension of stability of the protein and ligand complexes of compounds 3k, 4a, and 4c. The overall findings of the study indicated that N‐(pyridin‐2/3‐yl)alkanamide derivatives might be significant for the development of newer QS inhibitors.

Fatty acid synthesis promoted by PA1895-1897 operon delays quorum sensing activation in Pseudomonas aeruginosa

PA1895-1897 is a quorum sensing (QS) operon regulated by the anti-activator LuxR homologue QscR in Pseudomonas aeruginosa. We aimed to investigate its impact on bacterial metabolism, and whether it contributes to the delayed QS activation. We performed liquid chromatograph-mass spectrometer-based metabolomics using wildtype PAO1, PA1895-1897-knockout mutant, and mutant with pJN105.PA1895-1897 overexpression vector. The impact of metabolites on QS signaling molecule (3OC12-HSL and C4-HSL) concentrations, pyocyanin production, and QS gene (lasR, lasI, rhlR, and rhlI) expression was examined. Metabolomics analysis found that fatty acid biosynthesis had the highest fold enrichment among all metabolic pathways in PA1895-1897-overexpressed mutants. Among these enriched fatty acids, palmitoleic acid and acetic acid were the predominantly abundant ones that significantly affected by PA1895-1897 operon. When different doses of exogenous palmitoleic acid or acetic acid were added to the cultures of PA1895-1897 knockout mutants, their levels of 3OC12-HSL, C4-HSL, and pyocyanin were decreased in a dose-dependent manner. High doses of palmitoleic acid and acetic acid suppressed the mRNA expression of lasR, rhlR, and rhlI. Inhibition of fatty acid biosynthesis increased the production of 3OC12-HSL, C4-HSL, and pyocyanin in PA1895-1897-overexpressed cultures. Our data suggest that fatty acid synthesis is promoted by PA1895-1897 operon, and contributes the delayed expression of QS phenotypes, furthering the understanding about the regulation of bacterial QS activation.

Mechanistic insights into the orthogonal functionality of an AHL-mediated quorum-sensing circuit in Yersinia pseudotuberculosis

YpsR, a pivotal regulatory protein in the quorum-sensing (QS) of Yersinia pseudotuberculosis(Y. pstb), is essential for molecular signaling, yet its molecular mechanisms remain poorly understood. Herein, this study systematically investigates the interactions between YpsR and acyl-homoserine lactones (AHLs), shedding light on the selective mechanism of YpsR to various AHL molecules. Using molecular docking and surface plasmon resonance (SPR) analysis, we confirmed YpsR’s binding affinities, with the strongest observed for 3OC6-HSL, which notably inhibited Y. pstb growth. Additionally, we engineered a whole-cell biosensor based on YpsR-AHL interaction, which exhibited sensitivity to the signal molecule 3OC6-HSL produced by Y. pstb. Furthermore, key YpsR residues (S32, Y50, W54, D67) involved in AHL binding were identified and validated. Overall, this research elucidates the mechanisms of QS signal recognition in Y. pstb, providing valuable insights that support the development of diagnostic tools for detecting Y. pstb infections.

Impact of Quorum Sensing on the Virulence and Survival Traits of Burkholderia plantarii.

Quorum sensing (QS) is a mechanism by which bacteria detect and respond to cell density, regulating collective behaviors. Burkholderia plantarii, the causal agent of rice seedling blight, employs the LuxIR-type QS system, common among Gram-negative bacteria, where LuxI-type synthase produces QS signals recognized by LuxR-type regulators to control gene expression. This study aimed to elucidate the QS mechanism in B. plantarii KACC18965. Through whole-genome analysis and autoinducer assays, the plaI gene, responsible for QS signal production, was identified. Motility assays confirmed that C8-homoserine lactone (C8-HSL) serves as the QS signal. Physiological experiments revealed that the QS-defective mutant exhibited reduced virulence, impaired swarming motility, and delayed biofilm formation compared to the wild type. Additionally, the QS mutant demonstrated weakened antibacterial activity against Escherichia coli and decreased phosphate solubilization. These findings indicate that QS in B. plantarii significantly influences various pathogenicity and survival traits, including motility, biofilm formation, antibacterial activity, and nutrient acquisition, highlighting the critical role of QS in pathogen virulence and adaptability.

The bacterial quorum sensing signal 2'-aminoacetophenone rewires immune cell bioenergetics through the Ppargc1a/Esrra axis to mediate tolerance to infection.

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2'-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in murine macrophages' mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (Mpc1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (Esrra). Consequently, Esrra exhibits weakened binding to the Mpc1 promoter. This outcome arises from the impaired interaction between Esrra and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized murine and human macrophages. Exogenously added ATP in infected macrophages restores the transcript levels of Mpc1 and Esrra and enhances cytokine production and intracellular bacterial clearance. Consistent with the in vitro findings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association with PA persistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations and PA persistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the Ppargc1a/Esrra axis in its influence on Mpc1/OXPHOS-dependent energy production and PA clearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.

Complete genome sequence provides information on quorum sensing related spoilage and virulence of Aeromonas salmonicida GMT3 isolated from spoiled sturgeon

Foodborne bacteria can pose a threat to the public health due to their spoilage and virulence potential, which can be regulated by quorum sensing (QS) system. In the study, we isolated a spoilage bacteria strain Aeromonas salmonicida GMT3 from refrigerated sturgeon. The complete genome of A. salmonicida GMT3 was sequenced, and the QS related genes were assigned. QS signal molecules N-acyl-homoserine lactones (AHLs) and AI-2 were detected. Genes regulating the spoilage-related metabolic pathways, including protease and lipase secretion, amines metabolism, sulfur metabolism, motility and biofilm formation were analyzed. Furthermore, genes encoding for several virulence factors, e.g. hemolysin, aerolysin, type II secretion system (T2SS), type VI secretion system (T6SS), antibiotic and multidrug resistance were also identified. In addition, the spoilage and virulence phenotypes associated with QS including protease, swimming and swarming activity, biofilm and hemolytic activity were detected. This study provided new insights into spoilage and virulence mechanisms correlated with QS of A. salmonicida GMT3, which might promote development of new approaches for spoilage and virulence control based on QS target.

Design, synthesis, biological evaluation and in silico study of N-(Pyrimidin-2-yl)alkyl/arylamide derivatives as quorum sensing inhibitors against Pseudomonas aeruginosa.

The emergence of bacterial resistance to antimicrobial agents poses a serious threat to the effectiveness of treating bacterial illnesses. A major factor contributing to antimicrobial resistance is biofilm formation, driven by quorum sensing (QS). QS suppression inhibits the QS signaling pathway, obstructing cell-to-cell communication. This study focuses on N-(pyrimidin-2-yl)alkyl/arylamide derivatives, which were designed, synthesized, and characterized for their QS inhibitory effects. Among the synthesized compounds (3a-j), compounds 3b, 3d, and 3h exhibited the highest QS inhibitory activity, with inhibition zones of 17.66 ± 6.17, 14.00 ± 6.24, and 17.33 ± 0.66mm, respectively. Further, molecular docking studies revealed binding affinities between -8.4 and -6.3kcal/mol, indicating strong interactions with the target proteins. Moreover, molecular dynamic simulations confirmed the stability of the protein-ligand complexes for compounds 3b and 3h. Additionally, in-silico methods were employed to predict the physicochemical properties of these molecules. Overall, these findings underscore the potential of N-(pyrimidin-2-yl)alkyl/arylamide derivatives as QS inhibitors, offering a new perspective for developing alternative antimicrobial therapies.

The anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract and prediction of the roles of the potent phytocompounds

The leaves of Piper betle L., known as betel leaf, have immense medicinal properties. It possesses potent antimicrobial efficacies and can be a valuable tool to combat drug-resistant microorganisms. Quorum sensing (QS) inhibition is one of the best strategies to combat drug resistance. The present study investigates the anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract against two bacterial strains, Chromobacterium violaceum and Pseudomonas aeruginosa. The extract produced substantial QS-inhibition zones in a biosensor strain of C. violaceum (CV026), indicating interference with quorum-sensing signals. The Results demonstrated significant inhibition in biofilm formation and different QS-regulated virulence factors (violacein, exopolysaccharides, pyocyanin, pyoverdine, elastase) in both C. violaceum and P. aeruginosa at sub-MIC concentrations of the extract and tetracycline, an antibiotic with known anti-QS activity. The quantitative real-time PCR (qRT-PCR) revealed decreased gene expression in different QS-related genes in C. violaceum (cviI, cviR, and vioA) and P. aeruginosa (lasI, lasR, lasB, rhlI, rhlR, and rhlA) strains after treatment. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified the significant phytocompounds, mainly derivatives of chavicol and eugenol, in the extract. Of these compounds, chavicol acetate (affinity: −7.00 kcal/mol) and acetoxy chavicol acetate (affinity: −7.87 kcal/mol) showed the highest potential to bind with the CviR and LasR protein, respectively, as evident from the in-silico molecular docking experiment. The findings of this endeavour highlight the promising role of Piper betle L. as a source of natural compounds with anti-quorum sensing properties against pathogenic bacteria, opening avenues for developing novel therapeutic agents to combat bacterial infections.

N-acyl homoserine lactone cell-cell diffusible signalling in the Ralstonia solanacearum species complex.

Ralstonia solanacearum species complex (RSSC) includes soilborne bacterial plant pathogens with worldwide distribution and wide host ranges. Virulence factors are regulated via four hierarchically organized cell-cell contact independent quorum-sensing (QS) signalling systems: the Phc, which uses as signals (R)-methyl 3-hydroxypalmitate [(R)-3-OH PAME] or (R)-methyl 3-hydroxymyristate [(R)-3-OH MAME], the N-acyl homoserine lactone (AHL)-dependent RasI/R and SolI/R systems, and the recently identified anthranilic acid-dependent system. The unique Phc QS system has been extensively studied; however, the role of the two AHL QS systems has only recently been addressed. In this microreview, we present and discuss current data of the SolI/R and RasI/R QS systems in the RSSC. We also present the distribution and frequency of these AHL QS systems in the RSSC, discuss possible ecological roles and evolutive implications. The complex QS hierarchical networks emphasizes the crucial role of cell-cell signalling in the virulence of the RSSC.

Quorum sensing regulating the heterogeneous transformation of antibiotic resistance genes in microplastic biofilms

Microplastics (MPs) provide a specific habitat for bacterial adhesion and the adsorption of extracellular DNA (eDNA), making them hotspots for the transformation of antibiotic resistance genes (ARGs) in the environment. However, the heterogeneous mechanism of ARG regulation by quorum sensing (QS) in MP biofilms remains unclear. This study demonstrated that QS signals, including C8-HSL, 3-oxo-C10-HSL, and C12-HSL, were detected at ng/L levels in Bacillus subtilis biofilms colonized on MPs. The addition of these three AHLs enhanced natural transformation by 1–2 orders of magnitude in both MP and natural substrate (NS) biofilms, while QS inhibitors decreased transformation frequencies by 2 orders of magnitude. Moreover, transformation frequencies in MP biofilms increased 6.0-fold under QS regulation mediated by AHLs, compared to a 2.5-fold increase in NS biofilms. QS-regulated biofilm formation and EPS secretion were found to be responsible for ARG dissemination in MP biofilms, as indicated by the positive correlation between transformation frequencies and EPS variation. Additionally, mRNA expression analysis revealed that activation and inhibition of the QS system in MP biofilms regulated the expression of natural transformation-related genes, including epsG (regulating EPS secretion) and recO (regulating eDNA transformation). These results highlight the significant influence of the QS system on ARG dissemination through heterogeneous biofilm formation and EPS secretion in MP biofilms. Understanding the effect and mechanism of QS on ARG natural transformation provides new insights into controlling ARG spread by targeting QS in host bacteria within MP biofilms.

Cyanobacterial Bloom Formation by Enhanced Ecological Adaptability and Competitive Advantage of Microcystis-Non-Negligible Role of Quorum Sensing.

Microcystis-dominated cyanobacterial blooms (MCBs) frequently occur in freshwaters worldwide due to massive Microcystis colony formation and severely threaten human and ecosystem health. Quorum sensing (QS) is a direct cause of Microcystis colony formation that drives MCBs outbreak by regulating Microcystis population characteristics and behaviors. Many novel findings regarding the fundamental knowledge of the Microcystis QS phenomenon and the signaling molecules have been documented. However, little effort has been devoted to comprehensively summarizing and discussing the research progress and exploration directions of QS signaling molecules-mediated QS system in Microcystis. This review summarizes the action process of N-acyl homoserine lactones (AHLs) as major signaling molecules in Microcystis and discusses the detailed roles of AHL-mediated QS system in cellular morphology, physiological adaptability, and cell aggregation for colony formation to strengthen ecological adaptability and competitive advantage of Microcystis. The research progress on QS mechanisms in Microcystis are also summarized. Compared to other QS systems, the LuxI/LuxR-type QS system is more likely to be found in Microcystis. Also, we introduce quorum quenching (QQ), a QS-blocking process in Microcystis, to emphasize its potential as QS inhibitors in MCBs control. Finally, in response to the research deficiencies and gaps in Microcystis QS, we propose several future research directions in this field. This review deepens the understanding on Microcystis QS knowledge and provide theoretical guidance in developing strategies to monitor, control, and harness MCBs.

Quorum Quenching in Membrane Bioreactors for Fouling Retardation: Complexity Provides Opportunities.

The occurrence of biofouling restricts the widespread application of membrane bioreactors (MBRs) in wastewater treatment. Regulation of quorum sensing (QS) is a promising approach to control biofouling in MBRs, yet the underlying mechanisms are complex and remain to be illustrated. A fundamental understanding of the relationship between QS and membrane biofouling in MBRs is lacking, which hampers the development and application of quorum quenching (QQ) techniques in MBRs (QQMBRs). While many QQ microorganisms have been isolated thus far, critical criteria for selecting desirable QQ microorganisms are still missing. Furthermore, there are inconsistent results regarding the QQ lifecycle and the effects of QQ on the physicochemical characteristics and microbial communities of the mixed liquor and biofouling assemblages in QQMBRs, which might result in unreliable and inefficient QQ applications. This review aims to comprehensively summarize timely QQ research and highlight the important yet often ignored perspectives of QQ for biofouling control in MBRs. We consider what this "information" can and cannot tell us and explore its values in addressing specific and important questions in QQMBRs. Herein, we first examine current analytical methods of QS signals and discuss the critical roles of QS in fouling-forming microorganisms in MBRs, which are the cornerstones for the development of QQ technologies. To achieve targeting QQ strategies in MBRs, we propose the substrate specificity and degradation capability of isolated QQ microorganisms and the surface area and pore structures of QQ media as the critical criteria to select desirable functional microbes and media, respectively. To validate the biofouling retardation efficiency, we further specify the QQ effects on the physicochemical properties, microbial community composition, and succession of mixed liquor and biofouling assemblages in MBRs. Finally, we provide scale-up considerations of QQMBRs in terms of the debated QQ lifecycle, practical synergistic strategies, and the potential cost savings of MBRs. This review presents the limitations of classic QS/QQ hypotheses in MBRs, advances the understanding of the role of QS/QQ in biofouling development/retardation in MBRs, and builds a bridge between the fundamental understandings and practical applications of QQ technology.

Effect of L-HSL on biofilm and motility of Pseudomonas aeruginosa and its mechanism

Pseudomonas aeruginosa (P. aeruginosa) biofilm formation is a crucial cause of enhanced antibiotic resistance. Quorum sensing (QS) is involved in regulating biofilm formation; QS inhibitors block the QS signaling pathway as a new strategy to address bacterial resistance. This study investigated the potential and mechanism of L-HSL (N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide) as a QS inhibitor for P. aeruginosa. The results showed that L-HSL effectively inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa. The production of extracellular polysaccharides and the motility ability of P. aeruginosa were suppressed by L-HSL. C. elegans infection experiment showed that L-HSL was non-toxic and provided protection to C. elegans against P. aeruginosa infection. Transcriptomic analysis revealed that L-HSL downregulated genes related to QS pathways and biofilm formation. L-HSL exhibits a promising potential as a therapeutic drug for P. aeruginosa infection.Key points• Chemical synthesis of N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide, named L-HSL.• L-HSL does not generate survival pressure on the growth of P. aeruginosa and can inhibit the QS system.• KEGG enrichment analysis found that after L-HSL treatment, QS-related genes were downregulated.

Phenotypic memory in quorum sensing.

Quorum sensing (QS) is a regulatory mechanism used by bacteria to coordinate group behavior in response to high cell densities. During QS, cells monitor the concentration of external signals, known as autoinducers, as a proxy for cell density. QS often involves positive feedback loops, leading to the upregulation of genes associated with QS signal production and detection. This results in distinct steady-state concentrations of QS-related molecules in QS-ON and QS-OFF states. Due to the slow decay rates of biomolecules such as proteins, even after removal of the initial stimuli, cells can retain elevated levels of QS-associated biomolecules for extended periods of time. This persistence of biomolecules after the removal of the initial stimuli has the potential to impact the response to future stimuli, indicating a memory of past exposure. This phenomenon, which is a consequence of the carry-over of biomolecules rather than genetic inheritance, is known as "phenotypic" memory. This theoretical study aims to investigate the presence of phenotypic memory in QS and the conditions that influence this memory. Numerical simulations based on ordinary differential equations and analytical modeling were used to study gene expression in response to sudden changes in cell density and extracellular signal concentrations. The model examined the effect of various cellular parameters on the strength of QS memory and the impact on gene regulatory dynamics. The findings revealed that QS memory has a transient effect on the expression of QS-responsive genes. These consequences of QS memory depend strongly on how cell density was perturbed, as well as various cellular parameters, including the Fold Change in the expression of QS-regulated genes, the autoinducer synthesis rate, the autoinducer threshold required for activation, and the cell growth rate.

Design and analysis of quorum sensing language “Interpreter” ecosystem for microbial community

Microbes in diverse natural communities communicate via quorum sensing (QS) signals that act as microbial languages. QS-based communications have been reconstructed in two-strain microbiota for promising consortium-based applications. However, investigation and synthesis of multiple QS signals transmission in the QS communication network (QSCN) are less explored. In this study, QS language “interpreter” was proposed and constructed in five Escherichia coli strains to simulate the linear and circular QSCN among natural microbial communities. Specifically, by combining strain-level microscopic and bulk-level macroscopic measurements, we investigate the performances and dynamics of synthetic three-strain QS language “interpreter” ecosystems that are in response to dramatic environmental changes. Results of micro- and macroscopic experiments showed that the existence of complex QS language “interpreter” ecosystems promote the stability maintenance of microbial community. Furthermore, a comprehensive kinetic computational model was developed for the optimization of tunable directed QSCN. Finally, the perspectives of the QSCN for the effective control of microbial communities were discussed and summarized. This study revealed the dynamic control of complex microbial communications, contributing to ecosystem-based engineering and microbiome-based therapeutics.

Получение гетерологичных продуцентов рамнолипидов для промышленного производства высокоэффективного биосурфактанта

Rhamnolipids are promising microbial glycolipid biosurfactants that can be used as preparations for soil bioremediation in oil pollution. The expression of the rhamnolipid biosynthesis gene cluster in the main producer, Pseudomonas aeruginosa, is regulated by quorum sensing signals (QS). Complex biosynthesis regulation does not allow achieving high product yields. The production of heterologous rhamnolipid producers is a promising way to overcome the complex QS-dependent regulation of rhamnolipid biosynthesis, and also avoids the use of opportunistic Pseudomonas aeruginosa for the industrial production of rhamnolipids. Heterologous Escherichia coli BLWT-based producers with a transformant E14 productivity of 3.40±0.96 g/L were obtained on the basis of the plasmid vector pAl2–T with a construct from the native promoter and rhlAB genes, and Pseudomonas viridiflava AlC1223-based ones with the productivity of transformants P5, P6, P8 332.00±0.10, 200.00±0.10 and 180.00±0.10 g/L, respectively. The presence of rhlAB genes in the expression vector allows the obtaining monorhamnolipids for further use as an agent for the solubilization of soil hydrophobic pollutant (e. g. petroleum products), which will intensify bioremediation processes.

Dopamine, an exogenous quorum sensing signaling molecule or a modulating factor in Pseudomonas aeruginosa?

Pseudomonas aeruginosa is recognized globally as an opportunistic pathogen of considerable concern due to its high virulence and pathogenicity, especially in immunocompromised individuals. While research has identified several endogenous quorum sensing (QS) signaling molecules that enhance the virulence and pathogenicity of P. aeruginosa, investigations on exogenous QS signaling molecules or modulating factors remain limited. This study found that dopamine serves as an exogenous QS signaling molecule or modulating factor of P. aeruginosa PAO1, enhancing the production of virulence factors and biofilms. Compared to the control group, treatment with 40 μM dopamine resulted in a 33.1 % increase in biofilm formation, 68.1 % increase in swimming mobility, 63.1 % increase in swarming mobility, 147.2 % increase in the signaling molecule 3-oxo-C12-HSL, and 50.5 %, 28.5 %, 27.0 %, and 33.2 % increases in the virulence factors alginate, rhamnolipids, protease, and pyocyanin, respectively. This study further explored the mechanism of dopamine regulating the biofilm formation and virulence of P. aeruginosa PAO1 through transcriptome and metabolome. Transcriptomic analysis showed that dopamine promoted the expression of virulence genes psl, alg, lasA, rhlABC, rml, and phz in P. aeruginosa PAO1. Metabolomic analysis revealed changes in the concentrations of tryptophan, pyruvate, ethanolamine, glycine, 3-hydroxybutyric acid, and alizarin. Furthermore, KEGG enrichment analysis of altered genes and metabolites indicated that dopamine enhanced phenylalanine, tyrosine, and tryptophan in P. aeruginosa PAO1. The results of this study will contribute to the development of novel exogenous QS signaling molecules or modulating factors and advance our understanding of the interactions between P. aeruginosa and the host environment.