Descripción del proyecto
Elaboración de un perfil de un misterioso «guerrero» natural para contrarrestar la resistencia antimicrobiana
Pese a que pasan desapercibidas para la mayoría de las personas, en nuestro entorno se producen complejas batallas entre organismos unicelulares: las bacterias y los virus que «se las comen» (bacteriófagos). Ahora que la resistencia antimicrobiana supone un reto cada vez mayor para la salud pública, el aprovechamiento de estos asesinos bacterianos naturales representa una vía prometedora para las nuevas terapias. El problema es que, pese a que los bacteriófagos son los organismos más abundantes en la biosfera, hemos aislado muy pocos de ellos y contamos con escasos conocimientos sobre su funcionamiento. Todo esto está a punto de cambiar gracias al proyecto financiado con fondos europeos PHARMS. Los científicos cuentan con ambiciosos planes para encontrar todos los fagos posibles de un aislado bacteriano resistente, caracterizar los mecanismos de acción y utilizar esos conocimientos nuevos para diseñar un conjunto de herramientas terapéuticas basadas en fagos.
Objetivo
Emergence of antimicrobial resistance (AMR) is a grand scientific challenge of our time that has killed more than 700,000 people worldwide. Phage therapy, a promising complement to antibiotics, utilizes viruses of bacteria (bacteriophages) or phage-derived inhibitors as natural ways to fight AMR. The main obstacles in the clinical application of phage-based AMR therapy are the limited number of phage isolates and the unknown molecular mechanisms of phage-delivered bactericidal action. Building on the recent advances of my group in high-throughput, culture-independent but host-targeted methodologies, PHARMS aims to deploy a revolutionary approach: to screen for all possible phages of a resistant bacterial isolate, characterize multiple lines of their bactericidal functions, and use this information for the design of a whole battery of phage-based therapies that employ multifaceted modes of action.
Using an interdisciplinary research plan, PHARMS will discover phage-specific bactericidal action modes at all possible levels ranging from nucleotide sequence and transcription to translation, in order to elucidate the molecular mechanisms driving phage-mediated inhibition of AMR Acinetobacter baumannii, Helicobacter pylori, & Haemophilus influenzae (WP1). These discoveries, together with novel synthetic biology tools, will enable us to engineer an array of phage vectors that mimic phage-deployed bactericidal modes discovered under WP1, including transport of alien genes to deliver bactericidal effects (WP2). PHARMS will provide molecular confirmation and in vitro & in vivo validation of the functions of phage-encoded bactericidal peptides and enzymes (WP3). By elucidating universal and specific mechanisms of phage-delivered inhibition of AMR pathogens, PHARMS is positioned to provide the rational framework for the design of novel therapeutic strategies aimed at treating common and life-threatening infectious diseases.
Ámbito científico
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
85764 Neuherberg
Alemania