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Screening of N-Hexanamide and 2H-1,3-Benzodioxol Derivatives for Quorum Sensing Modulation in Chromobacterium violaceum

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Abstract—

The aim of the study was screening of chemical compounds library to find “quorum sensing” modulators in proteobacteria. The library included 19 molecules that contained the N-hexanamide non-polar radical or the 2H-1,3-benzodioxole polar heterocyclic group, which were partially identical to the natural autoinductor N-hexanoyl homoserine lactone (C6-AHL) chemical structure. The Chromobacterium violaceum CV026 (NCTC 13278) was used in “quorum sensing” modulation biotests. This biosensor strain is defective in the natural autoinducer C6-AHL biosynthesis, but contains the functional homodimeric protein CviR, which, after two C6-AHL molecules reception, activates the previously silent genes transcription, including the vioABCDE operon, which leads to the production of the blue-violet pigment violacein. The direct screening showed agonistic (violacein-inducing) activity in 4 compounds and the screening variant in presence of exogenously introduced C6-AHL indicated the antagonistic (violacein-inhibiting) activity in 9 tested compounds. Interestingly, the most pronounced antagonistic activity was found in molecules that proved to be C6-AHL agonists. Significantly, the effective concentrations of these compounds required for 50% violacein inhibition were 3.2–20.4-fold lower than ones causing 50% violacein induction. In addition, the absolute concentrations of the active compounds necessary for the induction of violacein were much higher than that of a natural autoinducer, and the degree of their inhibitory effect was inversely related to the concentration of C6-AHL exogenously introduced into the biotest. According to the screening results, N-1,3-benzodioxol-5-yl-oxohexanamide was identified as the most effective “quorum sensing” modulator, submitted for further in silico, in vitro and in vivo studies.

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Funding

The work was supported by the Russian Science Foundation, project no. 16-16-10048.

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Authors and Affiliations

  1. Federal Research Centre of Biological Systems and Agrotechnologies, Russian Academy of Sciences, 460000, Orenburg, Russia

    D. G. Deryabin & G. K. Duskaev

  2. Institute of Cellular and Intracellular Symbiosis, Ural Branch, Russian Academy of Sciences, 460000, Orenburg, Russia

    A. A. Galadzhieva

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  1. D. G. Deryabin
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  2. A. A. Galadzhieva
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  3. G. K. Duskaev
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Correspondence to D. G. Deryabin.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by P. Sigalevich

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Deryabin, D.G., Galadzhieva, A.A. & Duskaev, G.K. Screening of N-Hexanamide and 2H-1,3-Benzodioxol Derivatives for Quorum Sensing Modulation in Chromobacterium violaceum . Microbiology 89, 733–739 (2020). https://doi.org/10.1134/S0026261720050069

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