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Project titleAssessment of the potential of underexploited biodiversity as a source of biologically active compounds

AffiliationShemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences,

Research area 04 - BIOLOGY AND LIFE SCIENCES, 03-103 - Synthesis, structure, and properties of natural and physiologically active substances; medical chemistry and prediction of various types of biological activity

Keywordsantibiotics, biological activity, mass spectrometry, natural compounds, structure elucidation, microbiology, biotechnology

Annotation
The development of drug resistance in pathogenic microorganisms is a real threat in modern clinical practice. Even those infectious diseases that are considered conquered by mankind, such as plague and leprosy, can persist in unusual natural reservoirs and spread again. In hospital conditions, due to the accelerated selection of resistant strains of pathogens, hospital (nosocomial) strains of pathogens appear that are resistant to all known antibiotics. Septic complications caused by such pathogens jeopardize the very possibility of invasive operations and organ transplants, and the rate of introduction of new antimicrobial drugs into clinical practice lags far behind the rate of development of resistance to them. In this project, it is planned to apply the latest achievements in the field of metabolomics, microbiology and biotechnology to study the understudied natural sources of producer strains, as well as gain access to unculturable by classic meands microbial biodiversity. Natural isolates will be obtained, including by in situ cultivation methods, their antimicrobial activity and the spectrum of secondary metabolites will be studied.

Expected results
The project is an interdisciplinary research at the intersection of bioorganic chemistry and microbiology. As a result of the project, it is planned to characterize promising antibiotic producing strains, to study them from a microbiological and chemical point of view. The identification of the producers with high biotechnological potential is of great importance for the development of new antibiotics, since natural compounds remain the main source of new drugs introduced into clinical practice. The combination of approaches proposed in this project allows us to expect the identification of producers of new secondary metabolites with valuable pharmacological properties.

Annotation of the results obtained in 2023
During the period, the microbiota of different habitats were screened for antimicrobial activity. Both classical microbiological approaches and in situ cultivation techniques were used to isolate producer strains. Both freshwater samples and marine microbial communities were selected for in situ cultivation. Application of this approach allowed the isolation of 126 microbial strains, from which 9 most promising antimicrobial candidates were selected. Strains associated with mammals also turned out to be a valuable source of antimicrobial compound producers: more than 30 active strains were identified by sieving samples from the mucous membranes of beluga whales and pigs. Insect metabolites studied are also of interest: more than 30 candidates for metabolomic profiling were obtained by microbiological screening of bark beetle and Central Russian bee samples. The study of secondary natural metabolites with antimicrobial activity is relevant primarily from the point of view of searching for effector molecules with original mechanisms of action and targets in the cells of pathogenic microorganisms. The data on modern approaches to the study of the mechanisms of action of antibiotics and detection of resistance to them were summarized.

Publications

1. Baranova A.A., Tyurin A.P., Korshun V.A., Alferova V.A. Sensing of Antibiotic–Bacteria Interactions Antibiotics, 12, 8, 1340 (year - 2023) https://doi.org/10.3390/antibiotics12081340