Production and Pre-Clinical Study of the New Antifungal Antibiotics
Tech Area / Field
3 Approved without Funding
Russian Academy of Sciences / Center for Ecological Safety, Russia, St Petersburg
- Royal Military College of Canada, Canada, ON, Kingston\nHoshi University, Japan, Tokyo\nInstitute of Biotechnology, Spain, Leon
Project summaryObjective of the project is obtaining and studying new original by its structure and properties antifungal antibiotic highly active towards hardly-manageable yeast-like and mycelial fungi.
New antibiotic having no analogues in global medical practice can be used for treatment of fungal infections including systemic and visceral ones caused by pathogenic fungi resistant to the existing antifungal drugs.
To achieve this long-term objective, a complex study will be conducted which provides for fulfillment of complicated tasks on search and extraction of new not-known antifungal and antibacterial antibiotics from natural systems, development of methods for their extraction and purification, chemical identification, and assessment of biological activity. The studies also include the issues of microorganisms’ resistance to antibiotics. Of great scientific and practical interest is creation of complex preparations based on the extracted antibiotics and having components enhancing sensitivity of pathogens to antibiotics and allowing decreasing effective dose of the preparation.
While conducting search and extraction of antibiotic producers it is reasonable to focus on polyene antibiotics characterized by high antifungal activity and aimed at not ferment but ferment substrate. In this case, resistance must be rare and occur only due to several coordinated mutations in some genes.
SRCES RAS has a collection of live cultures of actinomycetes - highly active producers of new antifungal antibiotics. Of them, the most active strains which produce antibiotics with original structure not described in literature and characterized by not high level of toxicity will be selected and identified.
For that, methods for the strains extraction from producer biomass, purification and chemical identification will be developed. We plan to optimize technological conditions of producer cultivation for enhancing biomass productivity.
Novelty and high anti-fungal activity of antibiotic under development (no more than 1 µg/ml) will be confirmed by results of the studies on determination of spectrum of biological action against yeast-like fungi Candida including C. glabrata, C. crusei, C. lusitanie, which are troublesome due to their natural resistance to the existing antifungal drugs, to yeast-like fungi, which have secondary resistance to polyenes and azoles, and to a number of Aspergillus, Microsporium, Trichophyton genera fungi.
Strain-producer of new antibiotic will be subjected to comprehensive toxicological examination for harmlessness for warm-blooded animals. Toxicological trials of the strain-producer and produced raw fungicide material for assessment of harmlessness for warm-blooded animals will be conducted on laboratory animals (white mice and rats).
The project research team includes microbiologists, biochemists, biotechnologists, chemists, toxicologists; all of them have expertise in extraction of microorganisms-producers of different biologically active substances from ecosystems and in development of technologies for producing such metabolites.
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