Descripción del proyecto
Nuevas dianas moleculares contra las micobacterias
La resistencia a los antimicrobianos está aumentando su prevalencia y afecta a diversas bacterias, incluida «Mycobacterium tuberculosis». Para hacer frente a esta situación es necesario desarrollar nuevos fármacos que sean eficaces. El proyecto financiado con fondos europeos deCrYPtion tiene por objeto actuar sobre la familia de proteínas citocromo P450 (CYP) como estrategia terapéutica. El objetivo principal es proporcionar información fisiológica sobre diversos CYP que todavía no se han caracterizado funcionalmente. Un grupo de científicos analizará los CYP codificados por especies de micobacterias y vinculará su funcionamiento con vías biológicas específicas. Los resultados de deCrYPtion permitirán identificar nuevas dianas farmacológicas frente al género «Mycobacterium».
Objetivo
More than 190 species belong to the Mycobacterium genus. Among those, several are pathogenic to human and animals. The high number of human lives lost and the economic consequences of livestock infection are important incentives in the control and eradication of the responsible organisms. M. tuberculosis, one of the causative agents of tuberculosis (TB), is the most problematic representative: in 2016, 1.7 million deaths worldwide have been attributed to TB. Like for other infectious organisms, antibiotic resistances have appeared in Mycobacterium. Thus, there is a fundamental need to develop new antimycobacterial drugs. The inhibition of enzymes belonging to the Cytochrome P450 (CYP) protein family has been shown to suppresses the growth of several Mycobacterium species, making CYPs targets for drug development. Unfortunately, most CYPs are considered orphan: proteins for which no physiological function is known. The deCrYPtion action aims to define the physiological function of a selected set of mycobacterial CYPs. It will prove determinant in the development of new antibiotics. I will perform a large-scale comparative genomics analysis of the CYPs encoded by Mycobacterium species, in order to define orthologous groups and identify, for each, conserved partners and pathway context. This approach is extremely powerful (even if not frequently used) and allow to propose physiological functions, based on the information obtained. Specific CYPs to be characterized will be selected based on a set of stringent considerations, including their potential as drug targets. A preliminary analysis illustrates the approach that will be used. A combination of complementary biochemical, genetics and physiological experiments will be performed to validate the hypotheses generated. deCrYPtion will be undertaken within the Centre for Cytochrome P450 Biodiversity, under the supervision of Prof Steven Kelly, at Swansea University (Wales, United Kingdom).
Ámbito científico
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesbiological sciencesgenetics
- medical and health sciencesclinical medicinepneumologytuberculosis
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Programa(s)
Régimen de financiación
MSCA-IF-EF-RI - RI – Reintegration panelCoordinador
SA2 8PP Swansea
Reino Unido