2,5-Piperazinedione inhibits quorum sensing-dependent factor production in Pseudomonas aeruginosa PAO1.

The effects of 2,5-piperazinedione in reducing the production of quorum sensing (QS)-dependent factors in Pseudomonas aeruginosa PAO1 were assessed both in vitro and in vivo. 2,5-Piperazinedione exhibited a 69% reduction in the azocasein-degrading proteolytic activity and a 48% reduction in the elastolytic activity of PAO1. Further, it showed 85% and 96% reduction in the production of pyocyanin and extracellular polymeric substances (EPS) of PAO1, respectively. In the swimming inhibition assay, 2,5-piperazinedione-treated PAO1 cells exhibited poor swimming motility in swim agar medium. In the in vivo analysis, an enhanced survival of PAO1-preinfected Caenorhabditis elegans was observed after treatment with 2,5-piperazinedione. Regarding the mode of action, in the molecular docking analysis, 2,5-piperazinedione interacts with the amino acid residue of the LasR receptor protein required for binding the natural ligand N -3-oxododecanoyl-l-homoserine lactone (3-oxo-C12-HSL). This demonstrates the probability of 2,5-piperazinedione to interfere with the binding process of 3-oxo-C12-HSL to its receptor protein. Thus, the findings of the present study reveal the potential of 2,5-piperazinedione in reducing the QS-dependent phenotypic features of PAO1.

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