Bacterial structures involved in the modulation of antibiotic resistance

Peptidoglycan is a large polymer (10⁶ Da) and the main structural component of the bacterial cell wall. Its biosynthesis is the target of many antibiotics, including β-lactams (such as penicillin), one of the most widely prescribed classes of drugs. Understanding how this essential polymer expands and interacts with other macromolecular complexes, as well as how peptidoglycan is remodeled during bacterial growth is central to our research. We investigate the dynamics of peptidoglycan expansion in bacterial models with diverse shapes, combining genetic, biochemical, and microbiological approaches. A particular focus of our work is to decipher how peptidoglycan structure and synthesis are modulated in response to antibiotic stress. In parallel, we develop new molecules active against drug-resistant bacteria and explore the potential of approved drugs for the treatment of difficult infections, including mycobacterial infections. Our team brings together bacterial geneticists, biochemists, microbiologists, and medical doctors. We collaborate with chemists, structural biologists and specialists in host-pathogen interactions.

Recent works include: deciphering peptidoglycan expansion dynamics in Bacillus subtilis, Escherichia coli and Caulobacter crescentus; design of pro-drugs selectively activated by pathogens ; characterization of drug activity on live cells by NMR ; evaluation of new drug combo against Mycobacterium abscessus ; impact of drugs on bacterial metabolism by multi-omic approaches.