Descripción del proyecto
Nuevos antimicrobianos fotoactivables
La resistencia a los antimicrobianos es un problema sanitario importante, ya que favorece que muchos patógenos que antes eran susceptibles a los antibióticos ahora sean resistentes. Este fenómeno pone de manifiesto la necesidad de desarrollar fármacos nuevos. Para combatir la resistencia a los antimicrobianos, el proyecto PhotoLiB, financiado con fondos europeos, propone desarrollar fármacos lipídicos fotoactivables. La fotofarmacología, el empleo de la luz para modular las propiedades químicas de los fármacos, es un método prometedor ya que la luz no es tóxica y se puede administrar con alta precisión en puntos concretos. Los fármacos desarrollados por el equipo de PhotoLiB podrán penetrar y romper las membranas bacterianas, lo que ofrecerá alternativas seguras a los antimicrobianos existentes.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
WC1E 6BT London
Reino Unido