Gamma-lactones effects on growth and chemical communication in Chromobacterium subtsugae

Relevance. Currently, the search for natural compounds that inhibit density-dependent chemical communication in pathogenic bacteria is the most promising strategy for alternative antimicrobial chemotherapy. Goal of the study. Screening of chemically synthesized plant-derived gamma-lactone analogs for effects on growth and N-hexanoyl-L-homoserine lactone (C6-AHL) mediated chemical communication in a Chromobacterium subtsugae model. Material and methods. Five gamma-lactones containing a common five-membered oxolane ring and a linear alkyl radical of 2, 3, 4, 5, or 8 carbon atoms were included in the study. Genetically related strains of wild-type C. subtsugae ATCC 31532 and C6-AHL-deficient mutant C. subtsugae NCTC 13274 were model objects. The criteria for the gamma-lactones bioactivity were 50% suppression of bacterial growth and 50% inhibition of C6-AHL-dependent pigment violacein biosynthesis, respectively. Results. The inhibitory effect of gamma-lactones on chemical communication in bacteria was shown in the range from 1.04 mg/ml to 0.02 mg/ml against C. subtsugae ATCC 31532 and from 0.35 mg/ml to 0.02 mg /ml against C. subtsugae NCTC 13274, while the growth suppression required significantly higher concentrations. The intensity of these effects were directly proportional to the alkyl radical length in the screened molecules, increasing from short chain gamma-caprolactone to long chain gamma-dodecalactone. Conclusions. The nature of the anti-infective activity of medicinal plants containing gamma-lactones compounds is hypothesized. This point of view provides a perspective for an in-depth analysis of the gamma-lactone bioactivity mechanism, suggesting their interference with structurally similar AHLs in density-dependent chemical communication systems of bacteria.