Cyclodextrin-mediated quorum quenching in the Aliivibrio fischeri bioluminescence model system - Modulation of bacterial communication

Bacterial Quorum Sensing is a cell-to-cell communication process, in which, bacteria, performing cooperative behaviour, produce and detect extracellular signalling chemicals, to monitor cell population density. Numerous bacterial processes including bioluminescence, virulence factor production, biofilm formation etc. are known to be influenced by this bacterial communication network. Interest in QS systems has emerged in response to the fact that these processes have significant impact on the environment, human health as well as agriculture. Cyclodextrins-mediated quorum quenching is an innovative approach and the available information about their effects is very scarce. We selected Aliivibrio fischeri, a bacterium, producing light, based on Quorum Sensing, to be the first to investigate the cyclodextrins' effect on this bioluminescence. A systematic study was performed with twelve different cyclodextrin compounds in order to determine their concentration- and time-dependent bioluminescence inhibitory effect in the A. fischeri model system. Especially high quorum quenching effect was found for alpha-cyclodextrin: 10 mM alpha-cyclodextrin at 120 mM contact time which caused similar to 64% inhibition of bioluminescence. Experiments with the co-administration of alpha-cyclodextrin and N-(3-oxohexanoyl)-L-homoserine lactone, the signalling molecule of A. fischeri clearly showed, that the stimulating effect of this signal was diminished by alpha-cyclodextrin, suggesting, that complexation was responsible for the observed Quorum Sensing suppression. Although beta-cyclodextrin and its hydroxypropyl derivative significantly inhibited bioluminescence at as low as 0.156 mM concentration, their efficiency did not reach the level of alpha-cyclodextrin. According to our results, the autoinducer-dependent quorum sensing mechanism in Aliivibrio fischeri was markedly inhibited, the quorum quenching effect of cyclodextrins was clearly demonstrated. The efficiency was influenced by several parameters; the size of the interior cavity, the structure and the concentration of the cyclodextrins, as well as the contact time with the cells. The application of a cyclodextrin-trap for complexation of signal molecules may be a novel, promising method for influencing QS interfering strategies, for example, to enhance the efficiency of various biotechnologies, as well as to find alternative approaches against bacterial proliferation and infections. Furthermore, our results could also serve as a basis for further research with bacterial or plant model systems, in which the same chemical signals may induce physiological responses.