Description du projet
Frapper les bactéries là où ça fait mal
Staphylococcus aureus est une bactérie commune qui peut très bien vivre sur votre peau ou dans votre nez sans causer aucun dommage. Cependant, ces bactéries peuvent devenir mortelles si elles se retrouvent dans votre circulation sanguine, vos articulations, vos os, vos poumons ou votre cœur. Les infections à staphylocoques peuvent provoquer une intoxication alimentaire, une septicémie, un syndrome de choc toxique et même une arthrite septique. Connu pour sa capacité à résister aux antibiotiques, Staphylococcus aureus est un excellent système modèle pour élucider les mécanismes de tolérance aux antibiotiques. CheckBacZ utilise des méthodes de haute technologie pour évaluer les différentes étapes du cycle cellulaire de cette bactérie afin de trouver le moyen de la rendre vulnérable aux médicaments.
Objectif
The occurrence of multiple-drug resistant bacteria constitutes an important threat to healthy lives, signifying the importance of alternative strategies to combat bacterial infections. This research project bears the potential to significantly contribute to overcome antibiotic resistances that occur during the treatment of bacterial infections, as it combines the studies of cell division, cell cycle regulation and antibiotic resistance in the clinically relevant model Staphylococcus aureus. Given that the tubulin homologue FtsZ is essential for cell division and serves as an antibiotic resistance determinant in this organism, the proposed research activity focuses on the cytokinetic Z-ring, more precisely its role in driving the staphylococcal cell cycle. Super-resolution microscopy will be used to determine if FtsZ treadmilling controls the rate of cytokinesis and if it organizes the peptidoglycan synthesis proteins during cell division, aiming to provide evidence for a FtsZ-dependent checkpoint in the cell cycle. Profiting from a mutant screen currently ongoing in the host laboratory, mutants impaired in the timing of septum formation will be identified to study the functional integration of corresponding genes into FtsZ-driven septum synthesis. In view of the fact that bacteria at different stages of the cell cycle are phenotypically distinct, microfluidics will be used to test if the degree of antibiotic tolerance varies during the cell cycle, which would enforce the vision for re-sensitizing resistant bacteria by manipulating their cell cycle.
The strong expertise and the availability of cutting-edge techniques in the host group together with my professional experience will generate an ideal synergy within this work programme. I will generate valuable scientific knowledge, acquire transferrable skills and create new collaborations in the international bacterial cell biology community, thus paving the way for establishing myself as an independent researcher.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- natural sciencesbiological sciencescell biology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1099 085 Lisboa
Portugal