Description du sujet de thèse

The escalating occurrence of bacterial infections due to antibiotic-resistant pathogens presents a substantial threat to global health. In addition, enhancements to existing classes of antibiotics has struggled to keep up with the rapid emergence of resistance mechanisms. In this context, research efforts are increasingly focused on identifying novel antibacterial agents with unique mechanisms of action, a shift that has significantly spurred interest in antimicrobial peptides (AMPs) derived from microbiota.
The RUMCIBLE project aims at elucidating the functional properties of RumC1, an AMP from Ruminococcus gnavus of the human gut microbiota. RumC1, characterized by its distinct structural attributes, has shown effective interaction with the cell wall in the human pathogen Streptococcus pneumoniae. It also significantly reduces the metabolic activity of cell wall-assembling enzymes in actively growing cells. RUMCIBLE will further delineate the antibacterial mechanism of RumC1 at a molecular level in single-cells, along with its efficacy against various bacterial species. To this end, three complementary research axis will be conducted to decipher (i) where and how RumC1 accumulates in the cell wall of S. pneumoniae and other bacterial species; (ii) how bacterial cells die from RumC1 interaction with the cell wall and (iii) how can cells develop resistance to RumC1 toxicity. To achieve these objectives, a multidisciplinary approach combining molecular genetics, biochemistry, chemistry, and microscopy analysis, including high-resolution imaging techniques will be conducted. This wide range of methodologies will be carried out in an expert and complementary way by the host team at LMGM, in partnership with two CEA partner teams based in Grenoble to develop complementary approaches to super-resolution chemistry and imaging.

Contexte de travail

The project will be carried out in the 'Pneumococcal Competence and Transformation' team (https://cbi-toulouse.fr/fr/equipe-polard) at the Laboratoire de Génétique et de Microbiologie Moléculaire (LMGM) of the Centre de Biologie Intégrative (CBI), on the Paul Sabatier campus of the University of Toulouse.

Contraintes et risques

Part of the microbiology experiments will be carried out in the L2 safety laboratory.