Project description
Peptides that disrupt bacterial membranes
Antibiotic resistance occurs when bacteria evolve mechanisms to avoid being killed by one or multiple antibiotics. It poses a significant medical threat as it renders antibiotics ineffective, necessitating the development of novel treatments. The aim of the EU-funded PeptideKillers project is to design and test promising peptide therapeutics that are selective for bacteria and leave human cells unaffected. Researchers will model bacterial membranes and test various peptides for their ability to form pores and cause membrane disruption. PeptideKillers will lead to promising peptides with antimicrobial activity and offer the technology to expand membrane-targeting peptides against other pathogens or cells.
Objective
Antibiotic-resistant bacteria cause more than 700 000 deaths per year, and the forecast is 10 million per year in 2050. Moreover, emerging strains of bacteria resistant to all available antibiotics may lead to a global post-antibiotic era. Because of this threat, the WHO and the UN are encouraging the research and development of new treatments. The aim of this proposal is to design new peptides that selectively target and disrupt the membranes of pathogens but not those of human cells. To obtain such peptides, we will develop an innovative coarse-grained model of membranes and an original growth method, which will enable us to establish the relationship between peptide sequence motifs and their affinity to membranes with specific lipid compositions. Moreover, we will determine the critical peptide properties required for membrane disruption via the formation of transmembrane pores and spontaneous peptide translocation across membranes by devising new collective variables capturing these processes. Our computational advances will be complemented by experimental verification from peptide-membrane affinity measurements plus leakage and flip-flop fluorescence assays assessing membrane disruption. The most effective peptides will be evaluated for antimicrobial activity and human cell toxicity using growth inhibition and hemolytic assays, respectively. We will investigate mixtures of peptides for their synergistic increase in antimicrobial activity, and we will uncover the molecular mechanism of their synergism. The peptide behaviour will be quantified under equilibrium and more biologically relevant non-equilibrium conditions. The methods and knowledge obtained within this project will not only enable us to determine new peptides selectively killing bacteria, but will also enable the development of peptides targeted against membranes of enveloped viruses, cancer cells, or even cellular organelles with potential application as sensors, biomarkers, or therapeutics.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesclinical medicineoncology
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Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
601 77 Brno
Czechia