A number of bacteria that colonize the human body produce toxins and effectors that cause changes in the eukaryotic cell cycle—cyclomodulins and low-molecular-weight compounds such as butyrate, lactic acid, and secondary bile acids. Cyclomodulins and metabolites are necessary for bacteria as adaptation factors—which are influenced by direct selection—to the ecological niches of the host. In the process of establishing two-way communication with the macroorganism, these compounds cause limited damage to the host, despite their ability to disrupt key processes in eukaryotic cells, which can lead to pathological changes. Possible negative consequences of cyclomodulin and metabolite actions include their potential role in carcinogenesis, in particular, with the ability to cause DNA damage, increase genome instability, and interfere with cancer-associated regulatory pathways. In this review, we aim to examine cyclomodulins and bacterial metabolites as important factors in bacterial survival and interaction with the host organism to show their heterogeneous effect on oncogenesis depending on the surrounding microenvironment, pathological conditions, and host genetic background.

Recently, the search for new antimicrobial compounds, including the secondary metabolites of basidiomycetes, has become increasingly important. Representatives of this division of higher fungi have high biosynthetic abilities, which contributes to their use as producers. In this work, extracts of culture liquids and submerged mycelia from 18 strains representing three different orders of basidiomycetes were studied. For this purpose, the submerged cultivation of strains, extraction of biological material, and evaluation of the extract’s antimicrobial activity using the agar well diffusion method were carried out. The minimum inhibitory concentration was determined for extracts with strong activity. The most promising ones were analyzed using HPLC-MS. As a result, it was found that 16 strains contained antimicrobial metabolites. Thus, the strains selected for further work were Hericium corraloides 4, which showed not only the antibacterial but also antifungal activity of cultural liquid and submerged mycelia extracts, and Fomitopsis betulina 3, Fomitopsis pinicola 2, Hericium erinaceus 1, and Laetiporus sulphureus 4, whose cultural liquid extracts exhibited high antibacterial activity against Gram-positive and Gram-negative test cultures. For these strains, metabolic profiles were obtained using the method HPLC-MS. Using this method, two metabolites were preliminary identified: hericerin in H. erinaceus 1 and sulfureuine H in L. sulphureus 4.

Ribavirin and its analogues exhibit an in vitro antiproliferative effect in cancer cells. In this work, we studied the biological activities of a number of alkyl/aryloxymethyl derivatives of ribavirin’s aglycon—1,2,4-triazole-3-carboxamide. Alkyl/arylxymethyl derivatives of 1,2,4-triazole-3-carboxamide with substitutions at the fifth or first position of the triazole ring, were synthesized and their antiproliferative and antimicrobial effects were assessed. For both series, the presence of an antiproliferative effect was investigated, and 1-alkyl/aryloxymethyl derivatives were shown an antimicrobial potential against a Gram-positive bacteria Micrococcus luteus and Gram-negative bacterium Pseudomonas aeruginosa. The obtained results showed that the n-decyloxymethyl derivatives induced leukemia cell death at low micromolar concentrations. We confirmed that n-decyloxymethyl derivatives of ribavirin inhibited the cell cycle progression and induced an accumulation of leukemia cells in the subG1-phase. The molecular docking results suggest that alkyl/aryloxymethyl derivatives may act by inhibiting translation initiation, due to interference with eIF4E assembly. The outcome results revealed that active derivatives (1- or 5-n-decyloxymethyl-1,2,4-triazole-3-carboxamides) can be considered as a lead compound for anticancer treatments.

Background. Basidiomycetes have high biosynthetic capabilities. Their metabolites are capable of exhibiting antimicrobial properties, thereby being promising molecules for use in medicine or for further chemical transformation. The aim of the work. Evaluation of antibacterial and antifungal properties of culture liquid of basidiomycetes from the orders Agaricales and Polyporales, selection of active strains for further research. Materials and methods. The objects of the study were 10 strains of 10 basidiomycetes species from the orders Agaricales and Polyporales. Filtrates of culture liquids obtained as a result of submerged cultivation of fungi, their ethyl acetate extracts and post-extraction liquids were tested. The culture liquid of Fomitopsis betulina was also extracted with chloroform and butanol. Antibacterial and antifungal effects were studied by diffusion from wells into agar. Results. All the studied strains of basidiomycetes showed antibacterial activity. The highest activity against gram-positive and gram-negative bacteria was observed in strains of 3 species from the order Polyporales: Fomes fomentarius, F. betulina and F. pinicola. Antifungal activity was shown by 6 out of 10 studied cultures of basidiomycetes. The comparative series of extractants compiled by their effectiveness (ethyl acetate > butanol > chloroform) testified to the advantage of using polar solvents to extract antimicrobial metabolites of F. betulina from the its culture liquid. Conclusion. Three promising strains of basidiomycetes — producers of antimicrobial metabolites were selected.Among the studied species, representatives of the order Polyporales showed the greatest activity. Polar solvents extracted antimicrobial metabolites of F. betulina from its culture liquid more efficiently than non-polar chloroform. The obtained results demonstrate the ability of basidiomycetes to produce metabolites with antimicrobial properties. It is noted that species of the order Polyporales are more active than representatives of Agaricales.

The search for new antibiotics is an urgent problem due to the spread of resistance to existing antibacterial drugs in pathogenic microorganisms. Actinomycetes are producers of a large number of antibiotics used in medicine. Most antibiotics are isolated from actinomycetes of the Streptomyces genus, while rare genera of actinomycetes can be the producers of new antibiotics.The aim of the study is to investigate the effect of the biological substances complex present in aloe juice on the growth stimulation of rare genera of actinomycetes.Material and methods. Objects: samples of sod-podzolic soil and chernozem. The standard method of sowing soil suspensions on oat agar and Gause medium No. 2 was used to isolate actinomycetes. Chemotaxonomic properties were determined using the methods of ascending thin-layer chromatography on a cellulose layer. The generic identity of cultures was determined using Bergey’s manual and materials comparing the composition of cell walls of actinobacteria. DNA PCR with standard 27f and 1492r primers, as well as Sanger sequencing, were performed to study genosystematic features. Antibiotic activity was determined against the test microorganisms: Staphylococcus aureus ИНА 00985 (FDA 209P), Staphylococcus aureus ИНА 00761 (MRSA), Staphylococcus aureus ИНА 00762 (УФ- 2), Micrococcus luteus ATCC 9341, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Saccharomyces cerevisiae ИНА 01042.Results. A total of 527 actinomycete cultures were isolated from samples of sod-podzolic soil and chernozem with the addition of aloe juice; their phylogenetic position was determined. The dominant actinomycetes in the studied soil samples are the representatives of the genus Streptomyces. Bacteria of the genus Micromonospora take the second place by the number of isolated cultures. Rare genera of actinomycetes have also been identified: Nonomuraea, Streptosporangium, Nocardia, Actinomadura, Actinocorallia, Pseudonocardia, Amycolatopsis, Saccharomonospora, Saccharopolyspora, Promicromonospora, Kribbella. It was determined that the isolated cultures possess antibiotic activity against test microorganisms.Conclusion. It is advisable to use aloe juice after subjecting the leaves to biostimulation to isolate actinomycetes from the soil and identify their biodiversity.