Short Lecture "Molecular imaging of isolated Escherichia coli peptidoglycans allows insights into the mechanism of natural products inhibiting bacterial cell wall synthesis"

Emerging resistances of prokaryotic pathogens are one of the major challenges of today´s drug development research. Because of the decreasing efficacy of available antibiotic therapies against clinically relevant bacteria, innovative therapeutical options are urgently needed. Especially the unique prokaryotic cell wall is commonly known to constitute a highly relevant target for the development of antibacterial entities. Nevertheless, novel antibiotics inhibiting bacterial peptidoglycan synthesis are mostly missing today. This is primarily originated by difficulties in the kinetic assessment of single enzymes of the complex and co-dependent peptidoglycan synthesis machineries, e.g. the elongasome and divisome. Additionally, in the rather rare cases where a specific inhibitor of a murein synthesis enzyme was successfully identified, those leads were typically inactive against whole bacterial cells. With the intention to supply an alternative approach for the evaluation of leads potentially targeting bacterial cell wall synthesis, we present a facile and economic peptidoglycan isolation protocol allowing subsequent Atomic Force Microscopy- based molecular insights into peptidoglycan network ultrastructure. Applying this innovative technique, unprecedented insights into the mechanism of action of common peptidoglycan-targeting antibiotics as well as of the natural FtsZ-inhibitor berberin were established. This technique might serve as capable tool to evaluate or even identify novel inhibitors of peptidoglycan synthesis by an imaging-based approach.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023