Quorum Sensing Inhibitors Research Articles

Bioactivity of Citral and Its Nanoparticle in Attenuating Pathogenicity of Pseudomonas aeruginosa and Controlling Drosophila melanogaster

Plant-based essential oils are hydrophobic, volatile concentrate extracted from aromatic plants. They are the upcoming alternative and appealing source of antimicrobial compounds, citral (major constituent of lemongrass oil) being one of them, whose antiquorum sensing, in vivo delivery, and insecticidal potential need further exploration. Pseudomonas aeruginosa is one of the most prevalent, clinically lethal pathogens, which is resistible toward various treatments because of the inherent resistance acquired by the organism to many classes of drugs (multidrug resistant (MDR)). Moreover, fruit flies have been considered as the vectors of potentially lethal and opportunistic pathogens, including multiantibiotic-resistant microbes. As a result, controlling both the pathogen and its host vector are of utmost importance. The present study focused on the efficacy of essential oil of citral (EOC) and its nanoencapsulated form on quorum sensing inhibition (QSI) of P. aeruginosa PAO1 and its insecticidal activity against Drosophila melanogaster. Chitosan-based citral nanoparticles were synthesized and characterized using hydrodynamic size, zeta potential, polydispersity index, and field-emission scanning electron microscopy (FE-SEM). Citral nanoparticles at sub-minimum inhibitory concentration (MIC) exhibited QSI potential by attenuating biofilm formation (p-value < 0.05), while insecticidal activity of citral tested against D. melanogaster demonstrated toxicity of the EOC at a concentration of 3%–5%. Hence, the results elucidated the prospects of citral nanoparticles in the delivery of citral, which can be applied as a strategy to specifically target clinically lethal pathogens, major insect pests, and associated microbes.

Auranofin inhibits virulence pathways in Pseudomonas aeruginosa

Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence pathways in P. aeruginosa, including quorum sensing (QS) and Type IV pili (TFP). We show that auranofin acts via multiple targets, one of which being Vfr. Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.

Innovative microbial disease biocontrol strategies mediated by quorum quenching and their multifaceted applications: A review.

With the increasing resistance exhibited by undesirable bacteria to traditional antibiotics, the need to discover alternative (or, at least, supplementary) treatments to combat chemically resistant bacteria is becoming urgent. Quorum sensing (QS) refers to a novel bacterial communication system for monitoring cell density and regulation of a network of gene expression that is mediated by a group of signaling molecules called autoinducers (AIs). QS-regulated multicellular behaviors include biofilm formation, horizontal gene transfer, and antibiotic synthesis, which are demonstrating increasing pathogenicity to plants and aquacultural animals as well as contamination of wastewater treatment devices. To inhibit QS-regulated microbial behaviors, the strategy of quorum quenching (QQ) has been developed. Different quorum quenchers interfere with QS through different mechanisms, such as competitively inhibiting AI perception (e.g., by QS inhibitors) and AI degradation (e.g., by QQ enzymes). In this review, we first introduce different signaling molecules, including diffusible signal factor (DSF) and acyl homoserine lactones (AHLs) for Gram-negative bacteria, AIPs for Gram-positive bacteria, and AI-2 for interspecies communication, thus demonstrating the mode of action of the QS system. We next exemplify the QQ mechanisms of various quorum quenchers, such as chemical QS inhibitors, and the physical/enzymatic degradation of QS signals. We devote special attention to AHL-degrading enzymes, which are categorized in detail according to their diverse catalytic mechanisms and enzymatic properties. In the final part, the applications and advantages of quorum quenchers (especially QQ enzymes and bacteria) are summarized in the context of agricultural/aquacultural pathogen biocontrol, membrane bioreactors for wastewater treatment, and the attenuation of human pathogenic bacteria. Taken together, we present the state-of-the-art in research considering QS and QQ, providing theoretical evidence and support for wider application of this promising environmentally friendly biocontrol strategy.

Computational Design of Azine-Linked Hybrids of 2-Indolinone-Thiazolodine Scaffold as Novel and Promising Quorum Sensing Inhibitors

Microbial multidrug resistance is becoming a global menace to humanity, and finding alternative approaches to combat these “superbugs” is critical. Targeting quorum sensing (QS), which is essential for bacterial biofilm formation and virulence factors production, represents a viable alternative strategy for combating a variety of diseases. Accordingly, the current work reports potential QS inhibitors (QSIs), which could target the transcriptional regulator protein CviR in the model QS bacterium Chromobacterium violaceum. A set of novel hybrids 4(a–k) were synthesized using the virtual screening results of structurally based hybrids of the 2-indolinone-thiazolidine scaffold on the CviR active pocket residues. The ability of these hybrids to inhibit the QS system was tested against C. violaceum, and two molecules (4h and 4i) revealed promising antivirulence activity. Biofilm formation and motility were both impaired in the treated bacterial cells. Moreover, the molecular docking of these two compounds was comparable with that of chlorolactone (CL), a native inhibitor of the C. violaceum CviR. The global chemical descriptors were calculated for compounds 4h and 4i and found to be more reactive than the native inhibitor, CL. Furthermore, the in silico ADME prediction profiles of these two lead compounds, 4h and 4i, showed good ADME profiles.

The Role of Quorum Sensing Molecules in Bacterial-Plant Interactions.

Quorum sensing (QS) is a system of communication of bacterial cells by means of chemical signals called autoinducers, which modulate the behavior of entire populations of Gram-negative and Gram-positive bacteria. Three classes of signaling molecules have been recognized, Al-1, Al-2, Al-3, whose functions are slightly different. However, the phenomenon of quorum sensing is not only concerned with the interactions between bacteria, but the whole spectrum of interspecies interactions. A growing number of research results confirm the important role of QS molecules in the growth stimulation and defense responses in plants. Although many of the details concerning the signaling metabolites of the rhizosphere microflora and plant host are still unknown, Al-1 compounds should be considered as important components of bacterial-plant interactions, leading to the stimulation of plant growth and the biological control of phytopathogens. The use of class 1 autoinducers in plants to induce beneficial activity may be a practical solution to improve plant productivity under field conditions. In addition, researchers are also interested in tools that offer the possibility of regulating the activity of autoinducers by means of degrading enzymes or specific inhibitors (QSI). Current knowledge of QS and QSI provides an excellent foundation for the application of research to biopreparations in agriculture, containing a consortia of AHL-producing bacteria and QS inhibitors and limiting the growth of phytopathogenic organisms.

Modified N-acyl-L-homoserine lactone compounds abrogate Las-dependent quorum-sensing response in human pathogen Pseudomonas aeruginosa.

Quorum sensing (QS) is a mode of cell-cell communication that bacteria use to sense population density and orchestrate collective behaviors. The common opportunistic human pathogen Pseudomonas aeruginosa employs QS to regulate a large set of genes involved in virulence and host-pathogen interactions. The Las circuit positioned on the top of the QS hierarchy in P. aeruginosa makes use of N-acyl-L-homoserine lactones (AHLs) as signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL). Disabling QS circuits by certain small-molecule compounds, known as quorum-sensing inhibitors (QSIs), has been proposed as a strategy to attenuate bacterial pathogenicity. In this study, four new AHL analogs were designed by incorporating a tert-butoxycarbonyl Boc group in amide and β-keto (3-oxo) moiety. Compounds were evaluated on a molecular and phenotypic basis as a QSI using the screening strategy linked to the assignment of the Las QS system in P. aeruginosa. Using a LasR-based bioreporter, we found that the compounds decreased LasR-controlled light activity and competed efficiently with natural 3O-C12-HSL. The compounds reduced the production of the cognate 3O-C12-HSL and certain virulence traits, like total protease activity, elastase activity, pyocyanin production, and extracellular DNA release. Furthermore, a quantitative proteomic approach was used to study the effect of the compounds on QS-regulated extracellular proteins. Among the four compounds tested, one of them showed the most significant difference in the appearance of the 3O-C12-HSL-responsive reference proteins related to QS communication and virulence, i.e., a distinct activity as a QSI. Moreover, by combining experimental data with computational chemistry, we addressed the effect of LasR protein flexibility on docking precision and assessed the advantage of using a multi-conformational docking procedure for binding mode prediction of LasR modulators. Thus, the four new AHL compounds were tested for their interaction with the AHL-binding site in LasR to identify the key interferences with the activity of LasR. Our study provides further insight into molecular features that are required for small-molecule modulation of LasR-dependent QS communication in P. aeruginosa. This should facilitate rational design of the next generation of antivirulence tools to study and manipulate QS-controlled fitness in bacteria and, thereby, handle bacterial infections in a new way.

Formulation and Biological Evaluation of Quorum Sensing Inhibitor-Based Nanoemulsion against Resistant Pseudomonal Infections

Antimicrobial resistance has raised a serious concern due to the lack of therapeutics to control pathogenic infections. Pseudomonas aeruginosa is considered a multidrug-resistant pathogen and a leading cause of hospital-acquired infections. Anti-virulence approach mainly focuses on targeting bacterial virulence despite its growth and proves effective against such drug-resistant pathogens. In this study, we select a novel flavonoid compound, 7,8-dihydroxyflavone (DHF), which has been reported as a quorum sensing inhibitor (QSI) of P. aeruginosa, performed its in-silico studies to observe its binding affinity and potential interactions with the target protein (2UV0) and further developed it as a nano drug formulation (DHF-NF), and performed its in-vitro and in-vivo evaluation. The prepared DHF-NF was examined for its efficacy in the prevention of wound-associated surface infections of P. aeruginosa in rats. The DHF-NF was prepared by using homogenization and examined for several physical parameters. The prepared DHF-NF had a spherical shape and smooth topology. The microbiological assays demonstrated the inhibitory potential of DHF-NF in a dose-dependent manner. The histological analysis of Pseudomonas infected tissue of rat skin showed significant activity in animal group treated with DHF-NF as compared to control groups. The microbiological and in-vivo evaluation results revealed that the compound, DHF, showed strong inhibitory potential and suggest that the DHF-NF could be utilized as novel anti-QS and anti-biofilm therapeutics against Pseudomonal surface infections.

Current trends and advances of Quorum sensing inhibitors and their biotechnological applications

Serious setbacks were witnessed in shrimp farming, the food industry, and the ship industry during the past three decades primarily due to bacterial pathogens that coordinate by quorum sensing (QS). The influence of bacterial pathogens utilizing QS. The impact of QS cell communication on public health is extremely disastrous in terms of spread, spectrum, apart from their economic impact. The overuse of antibiotics has increased drastically to battle bacterial infections, including tons of antibiotics are distributed in the biosphere. Due to the indiscriminate use of antibiotics, multiple antibiotic-resistant strains have emerged, as the antibiotic resistance genes are being transferred to bacteria of terrestrial animals, humans, and pathogens. The increased public awareness of the negative drawbacks caused by over-exposure to antibiotics, also the emergence of multiple antibiotic resistant pathogenic stains led to the search for alternatives and unique solutions. One such unconventional, promising method is the interruption of bacterial cell to cell communication, which is currently termed QS inhibition. Now-a-days, QS inhibition is the potential objective for antimicrobial chemotherapy. This review summarizes the regulatory factors that attenuate the QS activities of deadly pathogens and discusses their distinctive characteristics. Improving awareness of the natural roles of regulatory elements might be useful in unveiling inhibitor applications to understand how QS is inhibited in pathogenic bacteria by different QS inhibitors.

Listening to enteric bacteria from the perspective of antibiotic alternatives in animal husbandry

<p>Antibiotic alternatives are urgently needed to combat the gut dysbiosis and antibiotic resistance due to the long-term use of antibiotics in farm animals and the slow growth of discovery of novel antibiotics. Interfering with bacterial cell-to-cell communication, known as quorum sensing (QS) is a promising strategy. QS inhibitors, or quenchers, can suppress various social activities and physiological processes, including the production of virulence factors and biofilm formation without inducing antibiotic resistance. There are dense microbes in the gut of animals, which communicate with each other as well as the hosts. The phenomena of QS in gut pathogens of farm animals is a novel area that deserves intense interest and further research. However, a few of studies have investigated QS changes in gut pathogens of farm animals, and validation of quenchers in animals is lacking. Combining antibiotic alternatives and antibiotics could achieve a synergistic effect, and improving our understanding of QS targets and developing databases for precision medicine could lead to more effective and safe use of quenchers. In this review, we summarized recent development of QS in farm animals and the mechanism of quencher used as antibiotic alternatives. Furthermore, the review concluded the advantage of using QS to fight against bacteria and put forward some perspectives for the future development of QS in antibiotics.</p>

α-Alkylidene δ-lactones inhibit quorum sensing phenotypes in Chromobacterium strain CV026 showing interaction with the CviR receptor.

Disruption of bacterial quorum sensing (QS) is presented as a promising strategy to overcome clinically relevant and phytopathogenic bacteria. This work presents α-alkylidene δ-lactones as new chemical scaffolds that inhibit the biosynthesis of violacein in the biosensor strain Chromobacterium CV026. Three molecules displayed higher than 50% violacein reduction when tested at concentrations lower than 625 µM. The most active α-alkylidene δ-lactone inhibited the hydrolysis of chitin concomitantly with the inhibition of violacein production in CV026, suggesting the disruption of its QS machinery. Further, RT-qPCR and competition experiments showed this molecule to be a transcriptional inhibitor of the QS-regulated operon vioABCDE. Docking calculations suggested a good correlation between binding affinity energies and inhibition effects, with all molecules positioned within the CviR autoinducer-binding domain (AIBD). The most active lactone yielded the best binding affinity energy, most probably due to its unprecedented binding with the AIBD. Our results show α-alkylidene δ-lactones as promising chemical scaffolds for the development of new QS inhibitors affecting LuxR/LuxI-systems.

In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in P. aeruginosa, allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population reaches a sufficient density, the accumulation of N-(3-oxododecanoyl) acyl homoserine lactone (3O-C12-HSL) leads to the activation of the LasR receptor, which then acts as a transcriptional activator of target genes involved in biofilm formation and virulence, thereby increasing the bacteria's antibiotic resistance and enhancing its virulence. In this study, we performed a structure-based virtual screening of a natural food database of 10 997 compounds against the crystal structure of the ligand-binding domain of the LasR receptor (PDB ID: 3IX4). This allowed us to identify four molecules, namely ZINC000001580795, ZINC000014819517, ZINC000014708292, and ZINC000004098719, that exhibited a favorable binding mode and docking scores greater than -13 kcal/mol. Furthermore, the molecular dynamics simulation showed that these four molecules formed stable complexes with LasR during the 150-ns molecular dynamics (MD) simulation, indicating their potential for use as inhibitors of the LasR receptor in P. aeruginosa. However, further experimental validation is needed to confirm their activity.

Use of whole-genome analysis to study the effect of various quorum-sensing inhibitors on the biofilm formation of Lactobacillus fermentum

To explore the effects of different quorum sensing inhibitors (QSIs) on the biofilm formation of Lactobacillus fermentum, a high-production signal molecule AI-2 screened by the research group, was taken as the research object and subjected to various QSIs. Three QSIs, namely 100 μmol/L d-galactose, 200 μmol/L d-ribose, and furanone, could inhibit the AI-2 activity of L. fermentum and the biofilm formation in a certain concentration range but not significantly affect the growth of the strain. Scanning electron microscopy and fluorescence microscopy revealed that each QSI did not significantly affect the bacterial cell morphology in planktonic and biofilm states at the optimal inhibitory final concentration, although they reduced the adhesion of the strain. The expression of luxS, a key gene of quorum sensing, was downregulated. When biofilm production increased, QSIs were added, and the activity of the AI-2 was consistent with the change in biofilm production. Whole-genome technology revealed that QSIs inhibited the expression of the luxS, resulting in restriction of pyruvate synthesis and downregulation of the expression of genes such as gapA, pgmB, ribBA, and ribF, which in turn affected the transport and metabolism of carbohydrates and coenzymes in the strain and ultimately reduced the biofilm formation of L. fermentum.

Inhibitory potential of some selected essential oils and their main components on the growth and quorum-sensing based pigment production of Serratia marcescens

"In this study the antibacterial potential of ten essential oils (EOs) and their main compounds against the development and quorum sensing (QS) mechanisms of the opportunistic bacterium Serratia marcescens was determined. The growth and QS inhibitory effect was evaluated by paper disc diffusion assay. The effect of EOs and components on QS-regulated prodigiosin biosynthesis was also studied. The results of our study indicated that some of the investigated EOs influenced the development and the QS-based activity of S. marcescens. Oregano and thyme oils showed the most pronounced antibacterial effect and had the strongest anti-QS potential. From the main oil compounds the phenolics, eugenol, carvacrol and thymol, proved to be efficient growth inhibitors. While eugenol and carvacrol had also a strong negative influence on AHL-mediated QS-systems in low concentrations, thymol was not effective in QS inhibition. Keywords: essential oils, quorum-sensing, prodigiosin."

Effects of Rhapontigenin as a Novel Quorum-Sensing Inhibitor on Exoenzymes and Biofilm Formation of Pectobacterium carotovorum subsp. carotovorum and Its Application in Vegetables.

The aim of this study was to devise a method to protect Chinese cabbage (Brassica chinensis) and lettuce (Lactuca sativa) from bacterial-disease-induced damage during storage. Thus, the potential of rhapontigenin as a quorum sensing (QS) inhibitor against Pectobacterium carotovorum subsp. carotovorum (P. carotovorum) was evaluated. The QS inhibitory effects of rhapontigenin were confirmed by significant inhibition of the production of violacein in Chromobacterium violaceum CV026 (C. violaceum, CV026). The inhibitory effects of rhapontigenin on the motility, exopolysaccharide (EPS) production, biofilm formation and virulence-exoenzyme synthesis of P. carotovorum were investigated. Acyl-homoserine lactones (AHLs) were quantified using liquid chromatography-mass spectrometry (LC-MS). The inhibitory effects of rhapontigenin on the development of biofilms were observed using fluorescence microscopy and scanning electron microscopy (SEM). A direct-inoculation assay was performed to investigate the QS inhibitory effects of rhapontigenin on P. carotovorum in Chinese cabbage and lettuce. Our results demonstrated that rhapontigenin exhibited significant inhibition (p < 0.05) of the motility, EPS production, biofilm formation, virulence-exoenzyme synthesis and AHL production of P. carotovorum. Additionally, the result of the direct-inoculation assay revealed that rhapontigenin might provide vegetables with significant shelf-life extension and prevent quality loss by controlling the spread of soft-rot symptoms. Consequently, the study provided a significant insight into the potential of rhapontigenin as a QS inhibitor against P. carotovorum.

Quorum sensing signals: Aquaculture risk factor

AbstractBacteria produce several virulence factors and cause massive mortality in fish and crustaceans. Abundant quorum sensing (QS) signals and high cell density are essentially required for the production of such virulence factors. Although several strategies have been developed to control aquatic pathogens through antibiotics and QS inhibition, the impact of pre‐existing QS signals in the aquatic environment has been overlooked. QS signals cause detrimental effects on mammalian cells and induce cell death by interfering with multiple cellular pathways. Moreover, QS signals not only function as a messenger, but also annihilate the functions of the host immune system which implies that QS signals should be designated as a major virulence factor. Despite QS signals' role has been well documented in mammalian cells, their impact on aquatic organisms is still at the budding stage. However, many aquatic organisms produce enzymes that degrade and detoxify such QS signals. In addition, physical and chemical factors also determine the stability of the QS signals in the aqueous environment. The balance between QS signals and existing QS signals degrading factors essentially determines the disease progression in aquatic organisms. In this review, we highlight the impact of QS signals on aquatic organisms and further discussed potential alternative strategies to control disease progression.

Drugs for the Quorum Sensing Inhibition of Oral Biofilm: New Frontiers and Insights in the Treatment of Periodontitis.

Chemical molecules are used by microorganisms to communicate with each other. Quorum sensing is the mechanism through which microorganisms regulate their population density and activity with chemical signaling. The inhibition of quorum sensing, called quorum quenching, may disrupt oral biofilm formation, which is the main etiological factor of oral diseases, including periodontitis. Periodontitis is a chronic inflammatory disorder of infectious etiology involving the hard and soft periodontal tissues and which is related to various systemic disorders, including cardiovascular diseases, diabetes and obesity. The employment of adjuvant therapies to traditional scaling and root planing is currently being studied to further reduce the impact of periodontitis. In this sense, using antibiotics and antiseptics involves non-negligible risks, such as antibiotic resistance phenomena and hinders the re-establishment of eubiosis. Different quorum sensing signal molecules have been identified in periodontal pathogenic oral bacteria. In this regard, quorum sensing inhibitors are emerging as some interesting solutions for the management of periodontitis. Therefore, the aim of this review is to summarize the current state of knowledge on the mechanisms of quorum sensing signal molecules produced by oral biofilm and to analyze the potential of quorum sensing inhibitors for the management of periodontitis.

Xanthene Derivatives Targeting Bacterial Efflux Pumps, Quorum-Sensing, and Biofilm Formation

The rise of multidrug resistance (MDR) bacteria in nosocomial and health-care institutions is widespread and is currently recognized as a major medical challenge. Mechanisms of bacterial resistance, namely, quorum sensing (QS), biofilm formation, and efflux pumps, have been identified as critical biological processes in MDR bacteria. Following previous reports on the activity of phenothiazines against mechanisms of bacterial resistance, in this work we focus on the synthesis of xanthene derivatives aiming to discover phenothiazine bioisosteres with improved activity. Four compounds were obtained from the conjugation of xanthydrol with sulfonamides and aniline and were fully characterized. Their antibacterial activity was assessed considering their minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative strains, efflux pump inhibition, influence on biofilm formation and quorum-sensing (QS) inhibition. It was observed that the MIC of all the tested compounds was above 64 µg/mL The four 9-xanthenyl derivatives obtained, particularly the xanthene sulfonamide derivatives 3b and 3c, showed promising results on QS inhibition with a reduction of pigment production of 48 and 41 mm, and on biofilm formation with a reduction of 78 and 79%, respectively.

Quorum-Sensing Inhibitors from Probiotics as a Strategy to Combat Bacterial Cell-to-Cell Communication Involved in Food Spoilage and Food Safety

Experience-based knowledge has shown that bacteria can communicate with each other through a cell-density-dependent mechanism called quorum sensing (QS). QS controls specific bacterial phenotypes, such as sporulation, virulence and pathogenesis, the production of degrading enzymes, bioluminescence, swarming motility, and biofilm formation. The expression of these phenotypes in food spoiling and pathogenic bacteria, which may occur in food, can have dramatic consequences on food production, the economy, and health. Due to the many reports showing that the use of conventional methods (i.e., antibiotics and sanitizers) to inhibit bacterial growth leads to the emergence of antibiotic resistance, it is necessary to research and exploit new strategies. Several studies have already demonstrated positive results in this direction by inhibiting autoinducers (low-molecular-weight signaling compounds controlling QS) and by other means, leading to QS inhibition via a mechanism called quorum quenching (QQ). Thus far, several QS inhibitors (QSIs) have been isolated from various sources, such as plants, some animals from aqueous ecosystems, fungi, and bacteria. The present study aims to discuss the involvement of QS in food spoilage and to review the potential role of probiotics as QSIs.

Graphene oxide/methyl anthranilate modified anti-biofouling membrane possesses dual functions of anti-adhesion and quorum quenching

Biofouling has always been a persistent problem impeding the applications of membranes in water treatment. Quorum sensing (QS) inhibitors are able to interfere with bacterial cell-to-cell communication to alleviate membrane biofouling, among which, methyl anthranilate (MA) aims at disrupting the Pseudomonas quinolone signal (PQS)-mediated QS system to inhibit biofilm formation. In this study, we developed a novel anti-biofouling membrane via immobilizing MA on graphene oxide (GO) nanocarrier, which was then successfully coated onto a polyvinylidene fluoride (PVDF) membrane through layer-by-layer assembly method. The introduction of QS inhibitor MA suppressed the expression of PQS synthesis gene pqsABCDE, N-acyl homoserine lactones (AHL) synthesis gene lasI, rhamnolipid synthesis gene rhlA and PQS receptor gene pqsR, thereby mitigating biofilm formation on the modified membrane. GO on membrane surface contributed to the reduction of bacterial initial adhesion. The synergistic effect of GO and MA endowed the modified membrane with dual resistance to biofouling. Compared with the virgin membrane, the extracellular polymeric substances (EPS), ATP and total cell fluorescence on GO/MA-PVDF membrane (GO:MA = 1:3, 5 layers) were substantially reduced by 50%, 73% and 86%, respectively, illustrating its excellent anti-biofouling capability. Notably, the incorporation of GO/MA was still efficient when treating real secondary effluent, with the evidence of lower flux decline and restrained biofilm formation. Taken together, we believe that GO/MA-PVDF membrane with both anti-adhesion and anti-biofilm capability has broad prospects for biofouling control in water treatment.

Bringing Antimicrobial Strategies to a New Level: The Quorum Sensing System as a Target to Control Streptococcus suis.

Streptococcus suis (S. suis) is an important zoonotic pathogen. It mainly uses quorum sensing (QS) to adapt to complex and changeable environments. QS is a universal cell-to-cell communication system that has been widely studied for its physiological functions, including the regulation of bacterial adhesion, virulence, and biofilm formation. Quorum sensing inhibitors (QSIs) are highly effective at interfering with the QS system and bacteria have trouble developing resistance to them. We review the current research status of the S. suis LuxS/AI-2 QS system and QSIs. Studies showed that by inhibiting the formation of AI-2, targeting the LuxS protein, inhibiting the expression of luxs gene can control the LuxS/AI-2 QS system of S. suis. Other potential QSIs targets are summarized, which may be preventing and treating S. suis infections, including AI-2 production, transmission, LuxS protein, blockage of AI-2 binding to receptors, AI-2-mediated QS. Since antibiotics are becoming increasingly ineffective due to the emergence of resistant bacteria, including S. suis, it is thus critical to find new antibacterial drugs with different mechanisms of action. QSIs provide hope for the development of such drugs.