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 signifi-cantly 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.