Coumarins are class of natural aromatic compounds based on benzopyrones (2H-1-benzopyran-2-ones). They are identified as secondary metabolites in about 150 different plant species. The ability of coumarins to inhibit cell-to-cell communication in bacterial communities (quorum sensing; QS) has been previously described. Coumarin and its derivatives in plant extracts are often found together with other small molecules that show anti-QS properties too. The aim of this study was to find the most effective combinations of coumarins and small plant-derived molecules identified in various plants extracts that inhibit QS in Chromobacterium violaceum ATCC 31532 violacein production bioassay. The coumarin and its derivatives: 7-hydroxycoumarin, 7.8-dihydroxy-4-methylcoumarin, were included in the study. Combinations of coumarins with gamma-octalactone, 4-hexyl-1.3-benzenediol, 3.4.5-trimethoxyphenol and vanillin, previously identified in oak bark (Quercus cortex), and eucalyptus leaves (Eucalyptus viminalis) extracts, were analyzed in a bioassay. When testing two-component compositions, it was shown that 7.8-dihydroxy-4-methylcoumarin, 4-hexyl-1.3-benzendiol, and gamma-octalactone showed a supra-additive anti-QS effect. Combinations of all three molecules resulted in a three- to five-fold reduction in the concentration of each compound needed to achieve EC₅₀ (half maximal effective concentration) against QS in C. violaceum ATCC 31532.

Quorum sensing inhibitors (QSIs) are an attractive alternative to antibiotic growth promoters in farmed animal nutrition. The goal of the study was the diet supplementation of Arbor Acres chickens with quercetin (QC), vanillin (VN), and umbelliferon (UF), which are plant-derived QSIs preliminarily showing cumulative bioactivity. Chick cecal microbiomes were analyzed by 16s rRNA sequencing, inflammation status was assessed by blood sample analyses, and zootechnical data were summarized in the European Production Efficiency Factor (EPEF). When compared to the basal diet control group, a significant increase in the Bacillota:Bacteroidota ratio in the cecal microbiome was found in all experimental subgroups, with the highest expression > 10 at VN + UV supplementation. Bacterial community structure in all experimental subgroups was enriched with Lactobacillaceae genera and also changed in the abundance of some clostridial genera. Indices of richness, alpha diversity, and evenness of the chick microbiomes tended to increase after dietary supplementation. The peripheral blood leukocyte content decreased by 27.9–45.1% in all experimental subgroups, likely due to inflammatory response reduction following beneficial changes in the cecal microbiome. The EPEF calculation showed increased values in VN, QC + UF, and, especially, VN + UF subgroups because of effective feed conversion, low mortality, and broiler weight daily gain.

The goal of the work was to analyze the ability of natural and semisynthetic penicillins to regulate the quorum sensing system in bacteria. The test strain was C. violaceumNCTC 13274 (CV 026)...

Chromobacterium spp. use a density-dependent cell-to-cell communication mechanism (quorum sensing, QS) to control various traits, including the pigment violacein biosynthesis. Recently, one of the type strains of this genus, previously deposited in the American Type Culture Collection under accession number C. violaceum 31532, was reclassified as C. subtsugae, making the QS data obtained for the first species irrelevant to the second. The goal of this study is to conduct transcriptomic and genomic analyses of the C. subtsugae ATCC 31532 (formerly C. violaceum ATCC 31532) strain to identify density-dependent regulated genes and the mechanisms of their QS control. Whole transcriptome dataset analysis comparing QS-negative mid-log phase and QS-positive early stationary phase samples revealed 35 down-regulated and 261 up-regulated genes, including 44 genes that increased transcription activity the most (log2 (fold change) > 4.0). In addition to the violacein biosynthesis, QS-controlled traits in C. subtsugae ATCC 31532 included the following: (i) cdeAB-oprM efflux pump; (ii) RND efflux transporter; (iii) chuPRSTUV iron acquisition system; (iv) polyamine transport system; (v) carbohydrate (semialdehydes) metabolic pathways; (vi) SAM/SPASM maturase system XYE (predicted); (vii) prophage proteins; and (viii) fucose-binding lectin II. Subsequent screening of the promoter regions of the up-regulated genes and operons in most cases showed the presence of CsuR AHL-receptor/transcriptional regulator binding sites with 56.25–68.75% similarity to the ideal 16-base-pair palindrome 5′-CTGTCCGATAGGACAG-3′ sequence, supporting the concept of QS control in C. subtsugae ATCC 31532 by the csuI-csuR gene pair. Notably, several transcriptional regulators (MarR, TetR/AcrR, HU family DNA-binding protein, helix-turn-helix domain-containing protein) were found to be under QS control. Based on these data, a hierarchical QS regulatory network in C. subtsugae ATCC 31532 was hypothesized that provides direct control of the target genes via a canonical autoinduction mechanism and further dissemination of the effect via the activity of QS-controlled transcriptional regulators.

Relevance. «Quorum sensing» (QS) plays an important role in the pathogenic potential realization of many malignant bacteria, and therefore is a promising direction for the in-depth study. It could provide the basis for the antibacterial agents creation of new operating principles. The use of plant extracts and small molecules identified in them is the one option to inhibit «quorum sensing» system, but this approach has certain limitations. In addition, the use of a limited number of bacterial biosensors leaves questions related to extrapolate data on the whole system and needs more research. Aim. Comparison of the QS-inhibitory activity of plant-derived molecules against the «quorum sensing» LuxI/LuxR-type system of the violacein-producing strain Chromobacterium subtsugae 026, as well as a panel of bacterial lux-biosensors. Material and methods. The work used a library of chemically synthesized analogues of plant-derived molecules, represented by quercetin, cinnamic aldehyde, 7-hydroxycoumarin, 4-hexylresorcinol and salicylic acid. The influence on the growing and the QS-inhibitory activity of the plant-derived molecules were evaluated using the serial dilution method. The QS-inhibitory effect of the studied compounds was determined according to the optical density measurement of the Chromobacterium subtsugae 026 strain extracted pigment and the measurement of bacterial lux-biosensors bioluminescence. Results. A panel of seven bacterial biosensors was used to screen the biological activity of quercetin, cinnamic aldehyde, 7-hyd-roxycoumarin, 4-hexylresorcinol and salicylic acid against four «quorum sensing» LuxI/LuxR-type systems. The unequal nature of the action of the studied compounds on the tested «quorum sensing» systems was demonstrated. It was found that the 4-hexylresorcinol QS-inhibitory action was most pronounced regarding Chromobacterium subtsugae 026, while the trans-cinnamaldehyde was more active regarding bacterial lux-biosensors. Conclusions. The presented work demonstrates the unequal nature of the action of the plant-derived molecules under study in relation to four differ-ent QS LuxI/LuxR-type systems. It has been suggested that this circumstance may be associated with a different mechanism of action of the studied substances on the bacterial cell. The results are of practical interest and require further study.