Description du projet
Des molécules de défense bactérienne pour lutter contre la résistance aux antibiotiques
Il devient de plus en plus difficile de traiter un nombre croissant d’infections, car les bactéries pathogènes deviennent résistantes aux antibiotiques. Bien qu’il s’agisse d’un processus naturel qui découle de la pression sélective exercée sur les bactéries, la mauvaise utilisation et la surutilisation des antibiotiques exacerbent le phénomène. Pour répondre au besoin immédiat de nouveaux médicaments antimicrobiens, le projet BACKSPiN, financé par l’UE, utilisera les bactériocines, des molécules de défense produites par certaines bactéries pour inhiber la croissance d’autres bactéries menaçantes. Les travaux seront axés sur le dépistage des bactériocines contre Streptococcus pneumoniae, un agent pathogène associé à la pneumonie. Le but ultime du projet est de générer un cocktail de bactériocines qui pourra être administré seul ou en combinaison avec d’autres antibiotiques pour traiter les agents pathogènes résistants.
Objectif
When the Noble Prize-winning Alexandre Fleming discovered antibiotics, he already noticed that microorganisms developed resistance mechanisms to survive. Therefore, he anticipated that a misuse of antimicrobial compounds to treat infections will drive the selection of hyper-resistant strains and the resurgence of almost-eradicated infectious diseases. Nowadays, the problem is so critical that the World Health Organization foresees that superbugs will outcompete cancer and cardiovascular diseases to become the first cause of mortality on the planet in less than 30 years (horizon 2050). Recently, the international organization drew a list of 10 priority pathogens that includes Streptococcus pneumoniae, a bacterium notorious in pneumonia (major upper respiratory tract infections), endocarditis, meningitis and brain abscess. To replace or restore antibiotic action, we thus need to find alternative strategies. In this proposal, I aim to use bacteriocins, small antimicrobial peptides secreted by bacteria, to kill S. pneumoniae. They are currently underexploited for human need but feature many valuable characteristics (e.g. efficiency, evolvability, specific spectrum, cheap/easy production, high sequence diversity, stability) complementary to antibiotics. I will test a collection of hundreds of bacteriocins and, according to their mode of action, will rationally assemble “overwhelming” bacteriocin cocktails to prevent emergence of resistance. In parallel, a tantalizing idea would be to exploit the beneficial bacteria of our microbiota and mobilize their bacteriocins to treat local infections. So, I will perform ex vivo infection of human epithelia with S. pneumoniae and test how bacteriocin-induced S. salivarius, a commensal bacterium of our gut, influences it. Besides generating valuable fundamental insight into the S. pneumoniae resistance mechanisms and infection cycle, the results of this project will also pave the way to fight against other notorious pathogens.
Champ scientifique
- medical and health sciencesclinical medicinepneumology
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1015 LAUSANNE
Suisse