Understanding How the Antimicrobial Peptide Thanatin Interacts with the Lipid Bilayer of Cell Walls Using Model Membranes

Due to a misuse of classical antibiotics, multi-drug resistant bacteria are spreading worldwide, increasing troubles related to the treatment of infectious diseases. Antimicrobial peptides are among the most suitable candidates to solve this problem since they induce little or no resistance and are active against a large spectrum of pathogens. Hundreds have been isolated from prokaryotes, plants and animals. In this study, we focus on the peptide thanatin which is naturally produced by the spined soldier bug, Podisus Maculiventris. Its activity against multiple Gram negative and Gram positive bacteria and fungi has already been reported (Fehlbaum, P., 1996). However, the mechanism underlying its bactericidal effect is still misunderstood.Since actual cell walls are not suited for most spectroscopic techniques due to their complexity, various mixtures of lipids were used to model the membranes of eukaryotic cells and bacteria. The effects of thanatin on multi- and unilamellar lipid vesicles were observed. 31P solid-state NMR allows the determination of the lipid head group dynamics and the vesicle morphology in the absence and presence of peptide. Dynamic light scattering and UV-vis spectroscopy were used to measure the aggregation of the vesicles induced by thanatin under different conditions. These results are in good agreement with the behavior of bacteria treated with thanatin in vivo. Complementary results on the order of the lipid acyl chains and the secondary structure of the peptide are obtained with infrared spectroscopy.