Project description
Targeting a novel mechanism in drug-resistant pathogens
Pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa represent major therapeutic challenges, as they can develop multidrug resistance. Antimicrobial resistance has escalated as a global health threat, necessitating the development of new antibiotics against novel, conserved bacterial processes crucial for survival but unaffected by resistance mechanisms. Funded by the Marie Skłodowska-Curie Actions programme, the TRANSPEPTID project focuses on trans-translation, a vital biological process found in bacteria that releases stalled ribosomes during protein synthesis. Researchers will engineer antimicrobial peptides to disrupt protein synthesis in resistant pathogens, offering new solutions in the face of antimicrobial resistance.
Objective
Antimicrobial resistance (AMR) poses a major threat to human health around the world. The AMR crisis has emerged as one of the leading public health threats of the 21st century. This global crisis is due to the fact that bacteria share and increasingly develop new resistance mechanisms as a consequence of the misuse of antibiotics, as well as a lack of new drug development. To combat this crisis, we need new classes of antibiotics, and most importantly, against new targets. It is therefore crucial to identify new molecular processes that can be targeted. Ideally, these should be: i) conserved among all pathogenic ESKAPE bacteria; ii) indispensable to bacterial survival or at least its fitness; iii) sufficiently variable that different species can be distinguished from each other; iv) absent in eukaryotes; v) not targeted by current antibiotics; vi) unrelated to existing AMR mechanisms; and finally, vii) reproducible in non- hazardous in vitro experiments. In this quest, trans-translation appears to be a perfect candidate. Development of new antibiotics that target trans-translation from multidrug resistant ESKAPE pathogens will be addressed in this project (TRANSPEPTID). We will use engineer antimicrobial peptides based on the C- terminal tails of SmpB proteins from ESPAKE pathogens with the propose to compete with endogenous SmpB, and in turn to inhibit trans-translation. The project is organized in three main objectives that will constitute three major breakthroughs in the field: (OB1) Optimization and characterization of designed peptides in ESKAPE pathogens, (OB2) Biophysical analysis of selected peptides in target ESKAPE pathogens, and (OB3) Determination of the high- resolution structures of the complexes between the peptides and their molecular targets by cryo-EM. Since TRANSPEPTID is a multidisciplinay project that embraces both fundamental and applied science, it will contribute significantly to strength the research and training profile of the researcher
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
You need to log in or register to use this function
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
35042 Rennes
France