Johanna Sofia Kallen

43 rue Buffon
24 allée des crapauds
75005 Paris
The discovery of new antibiotics and novel treatment modalities for bacterial infections has become a global priority, due to the challenge posed by antimicrobial resistances. The development of new antibiotics is of great importance, as we are running out of last-resort antibiotics. Antibiotic resistance spreads easily and can rapidly emerge following the introduction of a novel antibiotic. Consequently, there is an urgent need to identify compounds that attack new bacterial targets and that do not easily induce resistance.
The thesis focuses on ribosomally synthesised and post-translational modified peptides from the lasso peptide family. Lasso peptides are very small and exhibit a distinct topology resembling a lariat knot. The knot consists of a C-terminal tail that is threaded through a macrolactam ring, which is formed at the N-terminal site of the peptide. The distinct structure provides high stability and can be enhanced by disulfide bridges. The objective of this thesis is to investigate the structure-activity relationship between lasso peptides and potential bacterial targets, as well as their mode of action by studying their interaction with these targets.