Flore Miomandre PhD defense

Organic Chemistry & Interfaces (COrInt) team

Abstract
In light of the urgent threat posed by antibiotic resistance, this PhD project aims to develop new antibacterial peptides targeting an alternative mechanism: trans-translation. This process rescues bacterial ribosomes that have become stalled during protein synthesis and plays a crucial role in bacterial survival. Its specificity to prokaryotes makes it a particularly attractive target for the development of selective antibacterial agents.
More specifically, our strategy focuses on a specific region of the SmpB protein, a key player in trans-translation. By designing peptides that mimic this region, we seek to interfere with trans-translation, thereby offering a promising alternative therapeutic strategy.
This work demonstrates that a peptide derived from SmpB selectively and effectively inhibits trans-translation in vitro in E. coli. Its mechanism of action, involving competition with the native SmpB protein, has been investigated using cryo-EM. Structure–activity relationship studies subsequently guided the molecular optimisation of this initial candidate, leading to the identification of a promising antibacterial lead with optimised molecular features, including peptide length, while retaining substantial biological activity.

Jury
Olga IRANZO, CNRS Research Director, iSm2 (Marseille) / Reviewer
Éric ENNIFAR, CNRS Research Director, IBMC (Strasbourg) / Reviewer
Céline LANDON, CNRS Research Director, CBM (Orléans) / Examiner
Guillaume COMPAIN, Associate Professor, IECB (Bordeaux) / Examiner
François-Hugues PORÉE, Professor, ISCR (Rennes) / PhD Co-director
Reynald GILLET, Professor, IGDR (Rennes) / PhD Co-director
Charlène GADAIS, Associate Professor, ISCR (Rennes) / Supervisor

Contact
Flore Miomandre, flore.miomandre@univ-rennes.fr