Objective
The increasing prevalence of antibiotic-resistant microbes requires the development of new antimicrobials. Antimicrobial peptides (AMPs) are widely distributed effector molecules of innate immunity in animal kingdom that provide a first line of defense against an array of microorganisms. AMPs of animal origin may be an effective alternative or additive of conventional antibiotics for therapeutic use.
The main goal of the proposed project is search and investigation of novel AMPs of animal origin, and design of synthetic peptide molecules with improved antibiotic potency on the basis of discovered natural AMPs.
The proposed work is directed toward the isolation and comprehensive study of new AMPs from cells and tissues in animals belonging to different evolutionary groups: such as one of the most primitive group of invertebrates of phylum Cnidaria (jellyfish Aurelia aurita), invertebrates of phyla Annelidae (lugworm Arenicola marina) and Echinodermata (starfish Asterias rubens); and poikilothermal vertebrates, such as fish (sturgeon Acipencer guldenstadti) and reptilia (pond turtle Emys orbicularis).
The specific goals of the projects are:
- Purification of novel AMPs from cells and tissues of selected animals and their detailed structural characterization.
- Investigation of antimicrobial activity of discovered peptides against Gram-negative bacteria, Gram-positive bacteria and fungi including testing the ability of the peptides to keep their microbicidal activity upon physiological salt concentration.
- Study of cytotoxic activity of obtained novel AMPs against normal human cells (erythrocytes, lymphocytes, monocytes, neutrophils) and transformed mammalian cells.
- Investigation of mode of action of the most potent isolated antibiotic peptides on bacterial cells (pore formation, ions release, influence on bacterial metabolism, binding to cell surfaces or to their particular components). Study of the interaction of the peptides with mammalian cells using light and electron microscopy, and flow cytometry.
- Selection of the peptides with high activity against microorganisms and/or transformed human cells and low activity against normal human cells; structural -activity relationship analysis of these peptides.
- Design of novel artificial antibiotic peptides on the basis of discovered natural AMPs for improvement of microbicidal or antitumor activity of the peptides and decline of their hemolytic effects; with a special attention to detection of synergistic action of different AMPs or their combinations with conventional antibiotics against antibiotic-resistant pathogens.
The results of this study will provide valuable information for analysis of development of innate immunity factors upon evolution. It is expected to design synthetic potent antibiotic molecules, which can serve as templates for evaluation of novel therapeutic agents with improved efficacy for using in medicine and veterinary.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Funding Scheme
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Coordinator
53127 Bonn
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.