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Le contrôle qualité de la synthèse protéique comme cible pour le développement de nouveaux antibiotiques

Abstract : The current PhD work brings together various studies linked to bacterial protein synthesis. The first chapter is about the origins of protein synthesis at the time of the RNA world. This theoretical work continues with the presentation of a high-resolution structure of the elongation factor G (EF-G) in complex with the ribosome by cryo-electron transmission microscopy (cryo-TEM). We describe for the first time EF-G bound to the ribosome in the absence of any inhibitor. This particular structure of EF-G displays a yet unseen positioning of its third domain, which becomes very flexible. This study helps to understand the way the antibiotic fusidic acid blocks translation. The work then switches to a study of trans-translation, the main rescuing system of stalled ribosomes in bacteria. Trans-translation is generally vital or at least necessary for bacterial virulence. We conducted a preliminary structural study on the way faulty mRNAs are degraded during this process. This is why we present a study of trans-translation as a target for the development of new antibiotics. For this we developed and validated a reporter system for trans-translation, which is used to screen molecules targeting trans-translation.
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  • HAL Id : tel-01691728, version 1

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Kévin Macé. Le contrôle qualité de la synthèse protéique comme cible pour le développement de nouveaux antibiotiques. Génétique. Université Rennes 1, 2016. Français. ⟨NNT : 2016REN1B034⟩. ⟨tel-01691728⟩

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