Description du projet
Nouveaux antimicrobiens activés par la lumière
La résistance aux antimicrobiens pose un problème médical de plus en plus impérieux. En effet, de nombreux agents pathogènes auparavant sensibles aux traitements antibiotiques deviennent soudainement résistants. Cela montre clairement la nécessité de développer de nouveaux médicaments. Afin de lutter contre la résistance aux antimicrobiens, le projet PhotoLiB, financé par l’UE, propose de développer des médicaments à base de lipides pouvant être activés par la lumière. La photopharmacologie, à savoir l’exploitation de la lumière pour moduler les propriétés chimiques des médicaments, est une approche intéressante, dans la mesure où la lumière n’est pas toxique et peut être dirigée sur des sites spécifiques avec une grande précision. Les médicaments de PhotoLiB seront capables de pénétrer et de perturber les membranes bactériennes et offriront ainsi des alternatives sûres aux antimicrobiens existants.
Objectif
Antimicrobials have saved millions of lives since they were first discovered. Unfortunately, today the world is facing up a global antibiotic resistance health emergency. In fact, bacterial infections which have been susceptible to standard antibiotic regimes for decades are now becoming resistant to all major antimicrobial treatments, making their efficacy undermined. Within this context, this proposal aims to develop a new and original strategy to combat antimicrobial resistance. Photopharmacology is a novel and emerging medical approach which exploits light to modulate the activity of drugs. The energy of light, which is not toxic to humans and easily delivered with high precision, can be used to change, at will, the conformation and chemical properties of drugs, making them more selective and efficient. This project wants to apply the photopharmacology concept to amphiphilic lipid drugs, namely those molecules bearing a polar head and a lipid tail acting as antimicrobials through disruption of bacterial membranes. Since, unlike other proteins and enzymes, membranes cannot mutate, they are ideal targets to combat antimicrobial resistance. New Photoswitchable Amphiphilic Lipis (PALs), able to intercalate the bacterial membranes, will be developed and synthesised by inserting a photoactivable probe into a amphiphilic lipid. Upon light irradiation, these PALs will change conformation leading, selectively, to membrane damage and consequent cell death. A set of 20 PALs will be synthesised and the compounds will be evaluated against a panel of bacteria, alone or in synergistic combination with other antibiotics. Preliminary in-vivo studies on Galleria models will be carried out as well as NMR-metabolomic studies to elucidate the key interactions of PALs with living systems and the response of bacteria to the action of these new drugs. The data generated through this project will create new means and opportunities in the fight against bacterial resistance.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
WC1E 6BT London
Royaume-Uni