anti-QS Activity Research Articles

Inhibición de motilidad y Quorum sensing bacteriano por desechos de vinificación


 En la industria de alimentos, el biofilm es la principal causa de contaminación. Debido a normativas alimentarias, solo pocos compuestos pueden ser usados como conservantes o estar en contacto con alimentos durante su elaboración y a la vez deben ser económicos. Una alternativa es el uso de subproductos o residuos de agroindustrias. Una de las principales industria alimenticias de Iberoamérica es la vitivinicultura. La presente investigación utiliza orujo y escobajo de vino varietal Torrontés, para inhibir la virulencia bacteriana controlada por Quorum sensing (QS) y principalmente su motilidad (swarming y swimming), lo que permitiría el desplazamiento y formación de biofilm en alimentos. Realizamos extracciones con solventes de polaridad creciente (hexano, cloroformo, acetato de etilo y metanol). Enfrentamos 250 y 500 µg/ml de extractos (E) a las cepas de Pseudomonas aeruginosa ATCC 27853 y LVP65. Los E metanólicos de orujo y escobajo inhibieron más del 50 la motilidad swarming de ambas cepas. Los E acetato de etilo inhibieron swimming (25-30%). La actividad anti-QS de los E se ensayó con las cepas Chromobacterium violaceum ATCC 12472 y CV026. Determinando una inhibición de los E metanólicos y de acetato sobre el sistema de QS. Las bioactividades encontradas convierten a estos desechos en una novedosa alternativa para la preservación de alimentos

Chloroquine fumardiamides as novel quorum sensing inhibitors

Quorum sensing inhibitors (QSIs) that specifically interfere with bacterial cell-to-cell communication are considered as an alternative approach to conventional antibacterial therapy. In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-negative Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-negative, mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides. The initial screening of eighteen fumardiamides with primaquine, mefloquine and chloroquine scaffolds identified chloroquine derivatives as the most promising QSIs. Tail-group optimization of chloroquine fumardiamides led to the most active compounds 27, 29 and 30 bearing aminoethyl or piperidine moieties. At 400 µM concentration, these compounds inhibited the QS of C. violaceum strains in a manner similar to quercetin (the model QSI), while at the 40 µM concentration their inhibitory effect was twice less than that of quercetin. As none of the compounds displayed a bactericidal effect and that the QS inhibition was specific to the CV026 strain, our findings indicate that the structurally optimized chloroquine derivatives could function as quorum quenching (QQ) agents with a potential to block the signaling without entering the cell. In conclusion, our finding provides an important step toward the further design of agents targeting cell-to-cell communication.

Inhibitory activity of metal-curcumin complexes on quorum sensing related virulence factors of Pseudomonas aeruginosa PAO1

The use of metal complexes to reduce or inhibit virulence factors of Pseudomonas aeruginosa is a promising strategy for the management and control of infections caused by this multidrug-resistant pathogen. The present study aimed to investigate the anti-quorum sensing activity of sub-minimum inhibitory concentrations (sub-MIC) of copper(II) sulfate pentahydrate-curcumin complex (Cu-CUR), iron(III) nitrate nonahydrate -curcumin complex (Fe-CUR), zinc(II) chloride-curcumin complex (Zn-CUR) and free curcumin (free-CUR) against P. aeruginosa PAO1. Metal-CUR complexes were synthesized and characterized by spectroscopic methods. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of metal-CUR complexes and free-CUR on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of lasI and lasR genes in PAO1 was determined. MIC of metal-CUR complexes and free-CUR was determined as 62.5 and 125 µg/ml, respectively. Metal-CUR complexes at concentration of 62.5 µg/ml significantly reduced the cell growth to 1.5%–3.3%. Although we did not measure the anti-QS activity of metal-CUR complexes directly against PAO1, they indicated anti-QS activity in C. violaceum CV026. Copper-CUR complex at the concentration of 1/4 MIC showed the greatest inhibitory effect on swarming and twitching motilities, biofilm formation, alginate and pyocyanin production, sensitivity to H2O2 and reduction in the expression levels of lasI and lasR genes (P < 0.001). Considering the biological effects of Cu-CUR complex and its inhibitory activity on virulence factors, it may be used as an effective compound for treatment and control of infections caused by P. aeruginosa.

Bioactive Properties of Syzygium cumini (L.) Skeels Pulp and Seed Phenolic Extracts.

The emergence of bacterial strains resistant to different antibiotics has prompted the search for new sources of antimicrobial compounds. Studies have shown that jambolan [Syzygium cumini (L.) Skeels], a tropical fruit from the Mirtaceae family, contains a great variety of phytochemical compounds with high antioxidant and antimicrobial activity. This study aimed to determine the centesimal composition and physicochemical characteristics of the pulp and seed of S. cumini (L.) Skeels, as well as the content of total phenolic compounds and the antioxidant, antibacterial, antibiofilm and anti-quorum sensing (QS) activities of the phenolic extracts obtained from the pulp and the seeds of this fruit. The in vitro antibacterial and anti-QS activities of active films incorporating phenolic extracts were also evaluated. Additionally, we performed molecular docking of phenolic compounds present in jambolan with the CviR QS regulator of Chromobacterium violaceum. The composition and physicochemical characteristics of the samples presented similar values to those found for the species. However, the seed phenolic extract had a higher content of phenolic compounds and antioxidant activity than the pulp. Both phenolic extracts presented antibacterial activity against Aeromonas hydrophila, C. violaceum, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Serratia marcescens, Listeria monocytogenes, and Staphylococcus aureus. The seed phenolic extract was particularly inhibitory against S. aureus. The pulp phenolic extract inhibited swarming motility and biofilm formation of A. hydrophila, E. coli, and S. marcescens in sub-MIC concentrations. The pulp and seed phenolic extracts inhibited violacein production in C. violaceum. Films incorporating both phenolic extracts inhibited the growth of bacteria, particularly Pseudomonas fluorescens, L. monocytogenes, and S. aureus, as well as QS in C. violaceum. Molecular docking showed that a variety of compounds found in pulp and seed extracts of jambolan, particularly chlorogenic acid and dihydroquercetin, potentially bind CviR protein and may interfere with QS. Our results indicate that pulp and seed of jambolan are good sources of antibacterial, antibiofilm, and anti-QS compounds that can be used in the development of natural preservatives and for application in antibacterial active films.

Okanin in Coreopsis tinctoria Nutt is a major quorum-sensing inhibitor against Chromobacterium violaceum

Ethnopharmacological relevanceCoreopsis tinctoria Nutt has various medical and functional properties and its flower is widely used as health-care tea to decrease blood glucose and to lower blood lipids. However, the quorum sensing (QS) inhibition activity of Coreopsis tinctoria Nutt flower remains unclear.Aim of the study: To assess inhibitory activity against quorum sensing by Chromobacterium violaceum, to identify the chemical composition of the extracts and to disclose the action mechanism of separated compound. Material and methodsViolacein inhibition assays were performed in 96-wells microplates. The compounds extracted from Coreopsis tinctoria Nutt flower were separated and purified by various chromatography techniques. Respectively, thin layer chromatography (TLC, GF254), mass spectrometer (Agilent 1100 Series LC/MSD Trap SL), Medium-pressure automatic purification system (Buscisepacore C 620, Switzerland), High performance liquid chromatography (HPLC, Shimadzu LC-20AD, Japan), Liquid preparation Chromatography (Waters2545, USA). The chemical structures were identified by nuclear magnetic resonance (NMR, Bruker AV-500, Germany) technique. The inhibitory mechanism of okanin against C. violaceum quorum sensing was detected by quantitative real-time PCR (qRT-PCR). ResultsQuorum sensing regulates production of bacterial virulence factors, thereby making it an intriguing target for attenuating bacterial pathogenicity. In this study, anti-QS activity of Coreopsis tinctoria Nutt methanol fraction (CTM) was investigated against C. violaceum ATCC12472. CTM showed an inhibitory effect on the QS-mediated virulence factors production such as violacein in C. violaceum without effect on growth rate. Also, okanin was isolated from CTM and its potential of anti-QS was confirmed after observing a significant reduction of violacein production in C. violaceum. An attempt was made to assess the effect of okanin on vioABCDE expression in C. violaceum to disclose acting mechanisms. ConclusionsThe results of this study contribute to validate an inhibitory effect of Coreopsis tinctoria Nutt flower on quorum sensing by Chromobacterium violaceum and to determine the compound responsible for inhibition. Also, the inhibitory effect was achieved in tandem with the down-regulation of vio operon.

Tea polyphenols inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances resistance to Klebsiella pneumoniae infection in Caenorhabditis elegans model

Bacteria cells can communicate with each other via quorum sensing (QS) system. Various physiological characteristics including virulence factors and biofilm formation are controlled by QS. So interrupting the bacterial communication is an alternative strategy instead of antibiotics for control bacterial infection. The aim of this study was to investigate the effects of tea polyphenols (TPs) on quorum sensing and virulence factors of Klebsiella pneumoniae. In vitro study showed that the anti-QS activity of tea polyphenols against Chromobacterium violaceum in violacein production. At sub-MICs, TPs inhibited the motility, reduced protease and exopolysaccharide (EPS) production and also biofilm formation in K. pneumoniae. In addition, in vivo study showed that tea polyphenols at 200 μg/mL and 400 μg/mL increased the survival rate of Caenorhabditis elegans to 73.3% and 82.2% against K. pneumonia infection. Our findings suggest that tea polyphenols can act as an effective QS inhibitor and can serve as a novel anti-virulence agent for the management of bacterial pathogens.

Antibiofilm activity of coriander (Coriander sativum L.) grown in Argentina against food contaminants and human pathogenic bacteria

Bacterial spoilage of food and other infections are a coordinated mechanism controlled by quorum sensing (QS), which regulate the expression of virulence factors, such as biofilm. The antimicrobial, antibiofilm, anti-QS and anti-swarming properties of hexane (HE), chloroform (CE), ethyl acetate (EAE), methanolic (ME) and total methanolic (TME) extracts of coriander grown in Argentina were investigated. In vivo extracts toxicity using Galleria mellonella L. model and chemical composition (GC-MS) were also assessed. The antibiofilm activity of polystyrene surfaces coated with the most active extracts was evaluated. At non-inhibitory growth concentrations, extracts showed a strong antibiofilm capacity and a slight anti-swarming and anti-QS activities. Likewise, none of the extracts were toxic up to 2500 mg/kg. For all bacteria tested (Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Staphylococcus aureus), HE and CE of coriander were the most active extracts for inhibiting the formation and the metabolic activity of biofilm, especially for S. aureus. The anti-staphylococcal biofilm activity was confirmed by fluorescence and scanning electron microscopy. Extract-coated polystyrene surfaces decreased bacterial adhesion and subsequent biofilm formation, even after washing. A total of 11 and 14 chemical compounds were identified from the HE and CE, respectively, being oleic acid the main compound in both extracts. Particularly, the strong inhibitory activity of coriander HE against S. aureus biofilms is emphasizing. These results suggest the possible application of these extracts either as an antibiofilm agent or by generating anti-adherent surfaces in the food industry and in the clinical area.

Anti-Quorum Sensing Activity of Argentinean Honey and Effect of pH on Main Flavonoids

In this study, the anti-QS activity of regional floral honey from the southeast region of Argentina was investigated using the bacterial model (<em>Chromobacterium violaceum</em>. In addition, the anti-QS activity of quercetin, myricetin and luteolin was evaluated in an acidic medium. Two of the tested honey samples had the capacity to exert a notable anti-QS effect on (<em>C. violaceum</em>. The effect of quercetin on the anti-QS activity at pH 5.8 was higher than myricetin and luteolin. The results obtained from the identification of quercetin, myricetin and luteolin of the honey extracts by High-Performance Liquid Chromatography (HPLC) showed that quercetin was the main flavonoid followed by myricetin and luteolin. It was observed that honey with high values of quercetin and high value of free acidity, exerted a greater effect on the inhibition of QS. Thus, we can conclude that an umbral value of pH seems to be necessary to increase the anti-QS activity of quercetin.

Cladodionen Is a Potential Quorum Sensing Inhibitor Against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen using virulence factors and biofilm regulated by quorum sensing (QS) systems to infect patients and protect itself from environmental stress and antibiotics. Interfering with QS systems is a novel approach to combat P. aeruginosa infections without killing the bacteria, meaning that it is much harder for bacteria to develop drug resistance. A marine fungus Cladosporium sp. Z148 with anti-QS activity was obtained from Jiaozhou Bay, China. Cladodionen, a novel QS inhibitor, was isolated from the extracts of this fungus. Cladodionen had a better inhibitory effect than pyocyanin on the production of elastase and rhamnolipid. It also inhibited biofilm formation and motilities. The mRNA expressions of QS-related genes, including receptor proteins (lasR, rhlR and pqsR), autoinducer synthases (lasI, rhlI and pqsA) and virulence factors (lasB and rhlA) were down-regulated by cladodionen. Molecular docking analysis showed that cladodionen had better binding affinity to LasR and PqsR than natural ligands. Moreover, the binding affinity of cladodionen to LasR was higher than to PqsR. Cladodionen exhibits potential as a QS inhibitor against P. aeruginosa, and its structure–activity relationships should be further studied to illustrate the mode of action, optimize its structure and improve anti-QS activity.

EFFECT OF ETHYL PENTANOATE ON ANTI- QUORUM ACTIVITY OF EXTRACELLULAR PROTEIN SECRETED BY BACILLUS SUBTILIS ATCC11774

Antimicrobials agents at low concentration could stress out bacteria by inducing proteins production via regulating the transcription and translation process. The interruption of bacterial quorum sensing (QS), or cell-to-cell communication is known to have the potential to weaken the bacterial pathogenicity by inhibiting their communication. This study aims to explore the potential of synthetic antimicrobial compound, ethyl pentanoate in stimulating proteins production by Bacillus subtilis ATCC11774 as well as to determine the anti-QS activity of microbial proteins produced. The bacterial cells were exposed to 0.01 MIC of ethyl pentanoate in fermentation process at 37°C for 48 h and 72 h respectively. The proteins produced were further isolated and analyzed by using Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). Results showed that a new extracellular protein with approximate size of 15 kDa was produced by B. subtilis ATCC11774 after being treated with ethyl pentanoate at 37°C for 48 h and 72h. Despites of new protein band production, there was a deletion of protein band with approximate size of 18 kDa on protein synthesized at 72 h of fermentation. Whilst, the anti-QS activity of microbial proteins produced by B. subtilis at 37°C for 48 h and 72 h was determined by agar- wells diffusion assay, resulting “halo” inhibition zone ranged from 10.00 ± 1.00 to 10.33 ± 0.56 in diameter. Therefore, B. subtilis ATCC11774 in the presence of ethyl pentanoate at 0.01 MIC could regulate the extracellular protein production and expression. The isolated protein also exhibited anti-QS activity.

Relative assessment of anti-quorum sensing in Piper betle leaves extract via pyoverdin assay

Anti-quorum sensing property has been a popular alternative approach over bactericidal/bacteriostatic property in combating bacterial infection while simultaneously tackling the dilemma of antibiotic resistance. We presented pyoverdin assay as an initial screening to qualitatively determine the anti-quorum sensing activity in Piper betle by measuring the loss of absorbance at wavelength 630 nm. Growth of Pseudomonas aeruginosa was proven to be unaffected by the presence of the P. betle leaves extract. The regression value (R2) of the quorum sensing (QS) activity in untreated supernatant of P. aeruginosa was 0.9636 and we presented the QS activity in fold-change, normalized to untreated sample for a fair comparison between batch of assays. We further assessed the QS activity in the extracts of P. betle leaves and found the QS activity of P. aeruginosa grown in the presence of ethyl acetate extract at 200 μg/ml was reduced to 0.6-fold. As the concentrations went lower, higher fold of QS activity was observed, suggesting that P. betle leaves extract is demonstrating anti-QS activity at a higher concentration. Further fractionate of ethyl acetate crude extracts resulted in three fractionates with high anti-QS activity with >50% reduction in QS activity and five fractionates with intermediate anti-QS activity. The use of pyoverdin assay to qualitatively portray the anti-QS activity could shorten the lengthiness of extracting and measuring the signaling molecule yet, produces reliable information to screen for anti-QS activity and guide for further fractionation and purification of bioactive compound.

Senna alexandriana mill as a potential inhibitor for quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1

Background: Senna alexandriana Mill is a medicinally important plant used in laxatives and also possesses potent antimicrobial compounds, but its effect on the Pseudomonas aeruginosa was never analyzed. Aim: This study was carried out with the objective to attenuate quorum sensing (QS)-controlled virulence factors in P. aeruginosa and its biofilm. Methods: In the present study, acetone and hexane extracts of S. alexandriana mill were tested at sub-minimum inhibitory concentration concentrations for their anti-QS activity using bioreporter strain the Chromobacterium violaceum CV026. The effect of S. alexandriana Mill on different virulence phenotypes such as pyocyanin and protease production was investigated. Finally, the effect of the extract on P. aeruginosa, biofilm formation was also determined using the spectrophotometry-based method and microscopic analysis. Results: The extracts were tested for their activities against QS-controlled virulence factors of P. aeruginosa at 600 μg/ml and 800 μg/ml acetone and hexane extract concentration, respectively. Results showed that both the extracts have an inhibitory effect on different virulence factors of P. aeruginosa, including pyocyanin, protease production, and biofilm formation, without affecting the growth. The P. aeruginosa biofilm was found to be decreased by 75% and 62% in acetone and hexane extract presence. Conclusion: The results revealed that both acetone and hexane extracts showed anti-biofilm and anti-QS activity. It depicted the potential of S. alexandriana Mill against P. aeruginosa infection, its biofilm, and QS.

Anti-quorum sensing effects of licochalcone A and epigallocatechin-3-gallate against Salmonella Typhimurium isolates from poultry sources.

Quorum sensing (QS) is a cell density-dependent mechanism used by many pathogenic bacteria for regulating virulence gene expression. Inhibition or interruption of QS by medicinal plant remedies has been suggested as a new strategy for fighting against antibiotic-resistant bacteria. This study aimed to assess the impact of sub-inhibitory concentrations of licochalcone A (LAA) and epigallocatechin-3-gallate (EGCG) as natural plant products on the QS-associated genes (sdiA and luxS) expression. The PCR test was used to confirm the presence of sdiA and luxS genes in 23 S. Typhimurium isolates from poultry. The quantitative real-time PCR assay was used to analyze the expression of sdiA and luxS in S. Typhimurium isolates in response to the treatment with sub-inhibitory concentrations of LAA and EGCG at 45-min time point. All S. Typhimurium isolates showed the presence of sdiA and luxS genes (100%). As result, the expression of QS-related genes was significantly reduced in S. Typhimurium isolates following treatment with LAA and EGCG. In conclusion, LAA and EGCG showed anti-QS activity with down-regulation of both sdiA and luxS genes in S. Typhimurium, suggesting potential therapeutic use of them against salmonellosis. However, it must be pointed out that the safety and efficiency of these compounds need more thorough research.

Anti-quorum Sensing and Antimicrobial Effect of Mediterranean Plant Essential Oils Against Phytopathogenic Bacteria.

Essential oils (EOs) are one of the most interesting natural products extracted from different aromatic plants. For centuries, EOs have been considered an essential part of the traditional pharmacopeia. Many plant EOs have been reported as possible effective alternatives for commercial pesticides, and their single constituents have been used efficiently in food preservation for their promising anti-QS activity against several food pathogenic microorganisms. The current mini review gives a general overview over the microbicide effect as well as anti-quorum sensing and the anti-biofilm formation of some common plant EOs, especially those of Lamiaceae and Verbanaceae families; these are commonly grown in the Mediterranean region and are effective against some serious food phytopathogenic bacteria.

Plant-Derived Inhibitors of AHL-Mediated Quorum Sensing in Bacteria: Modes of Action.

Numerous gram-negative phytopathogenic and zoopathogenic bacteria utilise acylated homoserine lactone (AHL) in communication systems, referred to as quorum sensing (QS), for induction of virulence factors and biofilm development. This phenomenon positions AHL-mediated QS as an attractive target for anti-infective therapy. 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 vivo studies provide substantial knowledge about their modes of anti-QS activity. The current data about sulfur-containing compounds, monoterpenes and monoterpenoids, phenylpropanoids, benzoic acid derivatives, diarylheptanoids, coumarins, flavonoids and tannins were summarized; their plant sources, anti-QS effects and bioactivity mechanisms have also been summarized and discussed. Three variants of plant-derived molecules anti-QS strategies are proposed: (i) specific, via binding with LuxI-type AHL synthases and/or LuxR-type AHL receptor proteins, which have been shown for terpenes (carvacrol and l-carvone), phenylpropanoids (cinnamaldehyde and eugenol), flavonoid quercetin and ellagitannins; (ii) non-specific, by affecting the QS-related intracellular regulatory pathways by lowering regulatory small RNA expression (sulphur-containing compounds ajoene and iberin) or c-di-GMP metabolism reduction (coumarin); and (iii) indirect, via alteration of metabolic pathways involved in QS-dependent processes (vanillic acid and curcumin).

Protective effect of neglected plant Diplocyclos palmatus on quorum sensing mediated infection of Serratia marcescens and UV-A induced photoaging in model Caenorhabditis elegans

Plants are considered to be a leading source for possible human therapeutic agents. This holistic study has investigated the anti-quorum sensing (anti-QS), anti-infection, antioxidant and anti-photoaging properties of neglected plant Diplocyclos palmatus. The results showed that D. palmatus methanolic leaf extract (DPME) effectively inhibited the quorum sensing (QS) regulated virulence factor production as well as biofilm formation in Serratia marcescens. The transcriptomic analysis revealed that DPME significantly downed the expression of QS-regulated genes such as fimA, fimC, flhC, bsmB, pigP and shlA in S. marcescens, which supports the outcome of in vitro bioassays. Further, the docking study revealed that the presence of active compounds, namely tocopherols and phytol, DPME exhibited its anti-QS activity against S. marcescens. In addition, DPME treatment extended the lifespan of S. marcescens infected C. elegans by the action of dropping the internal accumulation. Further, qPCR analysis clearly revealed that DPME treatment significantly up-regulated the expression of the lifespan-related gene (daf-16) and immune-related genes (clec-60, clec-87, lys-7 and bec-1) in S. marcescens infected C.elegans. On the other hand, DPME extensively reduced the UV-A induced ROS stress, thereby, extended the lifespan in UV-A photoaged C. elegans. Further, the qPCR analysis also confirmed the up-regulation of daf-16, clec-60, clec-87 and col-19 genes which advocated the improvement of the lifespan, healthspan and collagen production in UV-A photoaged C. elegans. Further bioassays evidenced that that the lifespan extension of photoaged C. elegans was accomplished by the actions of antioxidants such as tocopherols and phytol in DPME.

Anti quorum sensing and anti virulence activity of tannic acid and it's potential to breach resistance in Salmonella enterica Typhi / Paratyphi A clinical isolates

Salmonella enterica Typhi and Paratyphi A are food borne pathogens causing typhoid, which is one of the most important food borne disease in the developing world. S. Typhi and S. Paratyphi A are of much concern as multi drug resistance has been on the rise. The current study is aimed to screen phytochemicals for anti quorum sensing (QS) activity against S. Typhi and S. Paratyphi A. Upon screening with swarming assay, tannic acid (TA) showed highest anti-QS activity with minimal concentration of 400μg/ml. The anti-QS activity of TA was confirmed with C. violaceum ATCC 12,472. TA showed 38–43% and 35–50% of inhibition in cell surface hydrophobicity and EPS production respectively. Through FTIR analysis, it has been observed that EPS of treated cells has a considerable change in protein and peptide. TA has also exhibited drastic reduction in the surfactant production as high as 85–90%. Blood sensitivity and antibiotic sensitivity assay revealed that TA significantly sensitizes the S. Typhi and S. Paratyphi A cells to immune components in human blood and antibiotics. It has reduced the resistance of S. Typhi and S. Paratyphi A cells against amikacin, ampicillin, ciprofloxacin, azithromycin, chloramphenicol and gentamycin, thus revitalized the usage of these antibiotics against drug resistant S. Typhi and S. Paratyphi A infections. The consistency of anti-QS potential of TA was further evaluated and established with another eight clinical isolates of S. Typhi and S. Paratyphi A. Thus TA has been proved as a promising anti QS agent that can be developed as a therapeutic combination against S. Typhi and S. Paratyphi A.

Study on Antibacterial and Quorum-Sensing Inhibition Activities of Cinnamomum camphora Leaf Essential Oil.

Many essential oils (EOs) regulate the quorum-sensing (QS) system of pathogens and inhibit the virulence expression. Interference with QS can potentially reduce bacterial multidrug resistance and aid the biological control of bacterial disease. In the present work, the antibacterial and anti-QS activities of Cinnamomum camphora leaf EO were investigated. A total of 23 chemical components with relative levels ≥0.11%, including a large number of terpene compounds, were identified in C. camphora leaf EO by gas chromatography–mass spectrometry (GC-MS). The principal component was linalool, followed by eucalyptol, with relative levels of 51.57% and 22.07%, respectively. The minimum inhibitory concentration (MIC) and antibacterial activity of C. camphora EO were examined, and P. aeruginosa and E. coli ATCC25922 showed the highest and lowest sensitivity to C. camphora EO, respectively. Tests of QS inhibitory activity revealed that C. camphora EO significantly decreased the production of violacein and biofilm biomass in C. violaceum, with the maximum inhibition rates of 63% and 77.64%, respectively, and inhibited the biofilm formation and swarming movement, independent of affecting the growth of C. violaceum. Addition of C. camphora EO also resulted in downregulation of the expression of the acyl-homoserine lactones (AHL) synthesis gene (cviI) and transcription regulator (cviR), and inhibited the expression of QS-regulated virulence genes, including vioA, vioB, vioC, vioD, vioE, lasA, lasB, pilE3, and hmsHNFR. Collectively, the prominent antibacterial activity and anti-QS activities clearly support that C. camphora EO acts as a potential antibacterial agent and QS inhibitor in the prevention of bacterial contamination.

Anti-quorum sensing and antibiofilm activities of Blastobotrys parvus PPR3 against Pseudomonas aeruginosa PAO1

The bacterial cell communication also termed as Quorum sensing (QS) system was involved in the expression of several virulence traits during Pseudomonas infection. The attenuating of this bacterial cell communication system is an attractive approach for the management of bacterial infections without the complication of resistance development. In this respect, the marine environment has gained significant attention due to its biodiversity and as a source of novel bioactive compounds. The present study aimed to screening effective QS inhibitors from marine associated fungal species for QS inhibitors. Twelve morphologically distinct fungal isolates were isolated from the wood of Avicennia marina from marine ecosystem. The anti-QS potential of fungal crude extract from was investigated in biosensor strain and test bacterium, Chromobacterium violaceum and Pseudomonas aeruginosa PAO1, respectively. Promising anti-QS activity was observed in the crude extract of one of the fungal isolate and identified by molecular characterization using internal transcribed spacer (ITS) region as Blastobotrys parvus PPR3. The anti-virulence and antibiofilm effects of ethyl acetate fractions from PPR3 against P. aeruginosa PAO1 were evaluated. The fungal metabolites responsible for the anti-QS activity of fungal crude extract was identified using gas chromatography-mass spectrometry (GC-MS). Furthermore, molecular docking studies were performed to understand the interaction of bioactive compounds with as receptors of P. aeruginosa PAO1. The crude extract of PPR3 showed reduction in different virulence traits of P. aeruginosa PAO1 such as production of pyocyanin, elastase, protease, chitinase, swimming and swarming motility, biofilm formation, exopolysaccharide production and alginate production at different sub-MIC concentrations. Interaction of bioactive metabolites with LasR and RhlR receptors of P. aeruginosa PAO1 was reported. The findings of the present study suggested that metabolites of B. parvus PPR3 interfere with QS system of P. aeruginosa PAO1 and alters the production of virulence factors.

Ibuprofen-mediated potential inhibition of biofilm development and quorum sensing in Pseudomonas aeruginosa

AimsPseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. Main methodsCFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. Key findingsIbuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SignificanceThe antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.