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

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

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%

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

Mean-field equation for a stochastic many-particle model of quorum-sensing microbial populations

We prove a mean-field equation for the dynamics of quorum-sensing microbial populations. In the stochastic many-particle process, individuals of a population produce public good molecules to different degrees. Individual production is metabolically costly such that non-producers replicate faster than producers. In addition, individuals sense the average production level in the well-mixed population and adjust their production in response ("quorum sensing"). Here we prove that the temporal evolution of such quorum-sensing populations converges to a macroscopic mean-field equation for increasing population sizes. To prove convergence, we introduce an auxiliary stochastic mean-field process that mimics the dynamics of the mean-field equation and that samples independently the individual's production degrees between consecutive update steps. This way, the law of large numbers is separated from the propagation of errors due to correlations. Our developed method of an auxiliary stochastic mean-field process may help to prove mean-field equations for other stochastic many-particle processes.Comment: 33 pages, 4 figure