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Invited Lecture

Antimicrobial Peptides: from the basic molecular mechanism of action to self-assembled nanopeptides against bacterial infections

Tuesday (18.06.2019)
09:00 - 09:30

It is generally believed that antimicrobial peptides, AMPs, are able to evade much of the bacterial resistance because they disturb the fundamental integrity of the entire cell by interfering with the life-defining cell membrane. However, there is no clear general consensus for the molecular basis by which AMPs act, although various structural models are proposed such as membrane deformation or pore formation. [1,2] In order to fully understand the mechanism, we embarked on a study to investigate both the structural and dynamic effects on model membranes. To this end we employed state-of-the-art Small-angle X-ray and neutron scattering (SAXS/SANS) methods which are capable to probe the structure of both lipids and peptide on nanometer length scales. In addition, by using H/D contrast variation scheme we could determine the lipid dynamics extracting both the transversal flip flop motion as well as lipid exchange. The results further show that indolicidin inserts on the interface between lipid tail/head on the outer leaflet without significant alteration of the membrane structure. However, the peptide perturbs the lipid packing causing an acceleration in the lipid dynamics. We speculate that the change in dynamics among others, leads to enhanced ion transport that causes depolarization and cell death.

In the second part of the talk, we will discuss recent advances in utilizing self-assembly and polymer conjugation as a tool to enhance the proteolytic stability and reduce the toxicity of these compounds.[4,5] Using these customized design of AMPs we aim to gain tunable control of both bactericidal activity and cytocompatibility and can potentially overcome the drawbacks of traditional AMPs.

 

References:

[1] H. Jenssen, P. Hamill and R. E. W. Hancock, Clinical Microbiology Reviews, 2006, 19, 491–511.

[2] W. C., Wimley, ACS Chemical biology 2010, 5 (10), 905-917.

[3] Nielsen, J. E., Bjørnestad, V. A., & Lund, R. Soft Matter, 2018, 11, 37–14.

[4 ] Xu, D., Jiang, L., Singh, A., Dustin, D., Yang, M., Liu, L. , Lund, R., and Dong, H.. Chem. Commun., 2015, 51(7), 1289–1292.

[5] Xu, D., Ran, Q., Xiang, Y., Jiang, L., Smith, B. M., Bou-Abdallah, Lund,R.; Li, Z.; and Dong, H. RSC Adv. 2016 6(19), 15911–15919.

Speaker:
Prof. Dr. Reidar Lund
University of Oslo