Specific quorum sensing-disrupting activity (A(QSI)) of thiophenones and their therapeutic potential

Disease caused by antibiotic resistant pathogens is becoming a serious problem, both in human and veterinary medicine. The inhibition of quorum sensing, bacterial cell-to-cell communication, is a promising alternative strategy to control disease. In this study, we determined the quorum sensing-disrupting activity of 20 thiophenones towards the quorum sensing model bacterium V. harveyi. In order to exclude false positives, we propose a new parameter (A(QSI)) to describe specific quorum sensing activity. A(QSI) is defined as the ratio between inhibition of quorum sensing-regulated activity in a reporter strain and inhibition of the same activity when it is independent of quorum sensing. Calculation of A(QSI) allowed to exclude five false positives, whereas the six most active thiophenones (TF203, TF307, TF319, TF339, TF342 and TF403) inhibited quorum sensing at 0.25 mu M, with A(QSI) higher than 10. Further, we determined the protective effect and toxicity of the thiophenones in a highly controlled gnotobiotic model system with brine shrimp larvae. There was a strong positive correlation between the specific quorum sensing-disrupting activity of the thiophenones and the protection of brine shrimp larvae against pathogenic V. harveyi. Four of the most active quorum sensing-disrupting thiophenones (TF 203, TF319, TF339 and TF342) were considered to be promising since they have a therapeutic potential of at least 10

Anti Quorum Sensing Activity of Kayu Manis Leaves Extracts (Cinnamomun Burmannii Ness. Ex Bl.) Against Pseudomonas Aeruginosa

Quorum sensing is a communication system among bacterial cells which correlates with biofilm formation. Biofilm can protect bacteria from environment including antibiotic of which can cause higher antibiotic concentration of 100 up to 1000 times. Inhibition of quorum sensing is expected to inhibit the biofilm formation. The cinnamon bark (Cinnamomum burmanii Ness. Ex Bl.) has been known to have antibacterial and antibiofilm activities. Leaves are available abundantly which urges a research to find out the activity as anti quorum sensing against Pseudomonas aeruginosa. The succesive maceration of dried pulverized leaves produced hexane, ethyl acetate, and methanol extracts. Antibacterial activity was observed by microdillution method with MTT assay. Afterwards, the active extract was examined for anti quorum sensing activity by diffusion method in cetrimide Agar. Quorum sensing activity was shown by dark zone (opaque) growth around sample application, observed under UV light of 366 nm. TLC bioautography method was done to observe the active spots by using silica gel F254 as the stationary phase, chloroform-methanol (6:1 v/v) as the mobile phase, loading sample used was 1.25 mg and 30 min of plate contact duration. The ethyl acetate extract inhibited growth of P. aeruginosa with shown by MIC at 8 µg/µL Quorum sensing as well as growth inhibition activities were observed at loading samples 12,5 and 25 mg/wells, while at 6,25 mg the extract only exhibited quorum sensing inhibition. Presences of substances having phenolic, flavonoid, alkaloid and aldehyde/keton as functional groups were detected by TLC method of the extract but no active spot identified on bioautography

Strength in numbers? Not always!

We propose a simple model to compute the probability of success under a quorum sensing strategy. We show that a quorum sensing strategy has a higher probability of success than an individualistic strategy when, for instance, the probability of success for a single individual is low and the cost of building a quorum is not too high. On the other hand if the cost of building a quorum is too high then the probability of success under quorum sensing always decreases as a function of the quorum

Screening of Indonesia Medicinal Plants Producing Quorum Sensing Inhibitor

Antibiotic resistance of bacteria lead to create different way in the pathogen bacteria handling such us inhibit their quorum sensing mechanism. The goal of this study is to search quorum sensing inhibitor of seven Indonesia medicinal plants. The experiment was conducted by extracting the plants using ethyl acetate subsequently tested on reporter carrying luxR homologous and luxCDABE genes. Reporter luminescence used as indicator of quorum sensing inhibition. The results show that ethyl acetate extracts of buah adas (Foeniculum vulgare), bunga lawang (Illicium verum), selasih (Ocimum basilicum), temu ireng (Curcuma aeruginosa), temu giring (Curcuma heyneana), dan temu lawak (Curcuma xanthorriza) mampu menginhibisi quorum sensing pada Pseudomonas aeruginosa. Further analysis was done by observing several metabolites which directly influenced by quorum sensing. The experiment was design by growth Pseudomonas aeruginosa at LB medium occurring fennel seeds ethyl acetate extract in the various concentration. Number of biofilms, rhamnolipid and activity of LasA produced by Pseudomonas aeruginosa were then measured. The experiment shown LasA activity inhibition reaching 100% was obtained at growth media containing 1.52 mg / ml extract. There was a decrease at inhibition activity when the extract concentration was added above this value. Meanwhile, 19% inhibition of rhamnolipid production occurred at concentrations of ethyl acetate extract of 2.03 mg / ml in growth media. Different results obtained in the production of biofilm which is induced by fennel seeds ethyl acetate extract at the level 123%

More Bang For Your Buck: Quorum-Sensing Capabilities Improve the Efficacy of Suicidal Altruism

Within the context of evolution, an altruistic act that benefits the receiving individual at the expense of the acting individual is a puzzling phenomenon. An extreme form of altruism can be found in colicinogenic E. coli. These suicidal altruists explode, releasing colicins that kill unrelated individuals, which are not colicin resistant. By committing suicide, the altruist makes it more likely that its kin will have less competition. The benefits of this strategy rely on the number of competitors and kin nearby. If the organism explodes at an inopportune time, the suicidal act may not harm any competitors. Communication could enable organisms to act altruistically when environmental conditions suggest that that strategy would be most beneficial. Quorum sensing is a form of communication in which bacteria produce a protein and gauge the amount of that protein around them. Quorum sensing is one means by which bacteria sense the biotic factors around them and determine when to produce products, such as antibiotics, that influence competition. Suicidal altruists could use quorum sensing to determine when exploding is most beneficial, but it is challenging to study the selective forces at work in microbes. To address these challenges, we use digital evolution (a form of experimental evolution that uses self-replicating computer programs as organisms) to investigate the effects of enabling altruistic organisms to communicate via quorum sensing. We found that quorum-sensing altruists killed a greater number of competitors per explosion, winning competitions against non-communicative altruists. These findings indicate that quorum sensing could increase the beneficial effect of altruism and the suite of conditions under which it will evolve.Comment: 8 pages, 8 figures, ALIFE '14 conferenc

Information processing and signal integration in bacterial quorum sensing

Bacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum-sensing network of the marine bacterium {\it Vibrio harveyi} employs three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within the three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration based on Information Theory and use it to analyze quorum sensing in {\it V. harveyi}. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input-output relation of the {\it V. harveyi} quorum-sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal-integration networks, and that bacteria likely have evolved active strategies for minimizing this interference. Here we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.Comment: Supporting information is in appendi

The Evolution of Quorum Sensing as a Mechanism to Infer Kinship.

Bacteria regulate many phenotypes via quorum sensing systems. Quorum sensing is typically thought to evolve because the regulated cooperative phenotypes are only beneficial at certain cell densities. However, quorum sensing systems are also threatened by non-cooperative "cheaters" that may exploit quorum-sensing regulated cooperation, which begs the question of how quorum sensing systems are maintained in nature. Here we study the evolution of quorum sensing using an individual-based model that captures the natural ecology and population structuring of microbial communities. We first recapitulate the two existing observations on quorum sensing evolution: density-dependent benefits favor quorum sensing but competition and cheating will destabilize it. We then model quorum sensing in a dense community like a biofilm, which reveals a novel benefit to quorum sensing that is intrinsically evolutionarily stable. In these communities, competing microbial genotypes gradually segregate over time leading to positive correlation between density and genetic similarity between neighboring cells (relatedness). This enables quorum sensing to track genetic relatedness and ensures that costly cooperative traits are only activated once a cell is safely surrounded by clonemates. We hypothesize that under similar natural conditions, the benefits of quorum sensing will not result from an assessment of density but from the ability to infer kinship

Implications of Rewiring Bacterial Quorum Sensing

Bacteria employ quorum sensing, a form of cell-cell communication, to sense changes in population density and regulate gene expression accordingly. This work investigated the rewiring of one quorum-sensing module, the lux circuit from the marine bacterium Vibrio fischeri. Steady-state experiments demonstrate that rewiring the network architecture of this module can yield graded, threshold, and bistable gene expression as predicted by a mathematical model. The experiments also show that the native lux operon is most consistent with a threshold, as opposed to a bistable, response. Each of the rewired networks yielded functional population sensors at biologically relevant conditions, suggesting that this operon is particularly robust. These findings (i) permit prediction of the behaviors of quorum-sensing operons in bacterial pathogens and (ii) facilitate forward engineering of synthetic gene circuits

Regulation of virulence factors by quorum sensing in Vibrio harveyi.

Vibrio harveyi is an important aquatic pathogen that produces several virulence factors. In this study, the effect of quorum sensing, bacterial cell-to-cell communication, on the production of the virulence factors caseinase, gelatinase, lipase, hemolysin, and phospholipase, was investigated. The activity of virulence factors was studied through enzymatic plate assays using V. harveyi wild type and mutants with constitutively maximal or minimal quorum sensing activity. The results showed that quorum sensing negatively regulates phospholipase activity as higher activity was observed in mutants with minimal quorum sensing activity than in the mutant with maximal quorum sensing activity. Reverse transcriptase real-time PCR with specific primers revealed that the expression level of three phospholipase genes was 2-fold lower in the mutant with minimal quorum sensing activity than in the mutant with maximal quorum sensing activity. As far as we know, this is the first report of quorum sensing regulation of phospholipase. Finally, caseinase and gelatinase activity were positively regulated by quorum sensing, which is consistent with previous reports, and lipase and hemolysin activity were found to be independent of quorum sensing. Hence, the regulation is different for different virulence factors, with some being either positively or negatively regulated, and others being independent of quorum sensing. This might reflect the need to produce the different virulence factors at different stages during infection