The rapid growth of antibacterial resistance and the glooming predictions that it will become the leading cause of mortality has created an urgent need for novel antibiotics. To this end, antimicrobial peptides (AMPs) are promising alternatives due to their high potency and broad scope activity. However, despite their great promise, AMPs have seen little clinical use, which is largely due to their cytotoxicity and susceptibility to peptide degrading enzymes, in addition to the poor understanding of how they work. While it is largely accepted that AMPs perturb the bacterial cell membrane, there is little consensus of how they do this.

This HALRIC pilot project aims to uncover the mechanisms of AMPs and contribute to overcoming one of the major hurdles towards developing AMP-based antibiotics. The cross-border research team from the University of Oslo and MAX IV Laboratory will use a combined setup of small angle X-ray scattering with in situ fluorescence spectroscopy at the coSAXS beamline at MAX IV, to map the insertion of several different AMPs into the membrane, while simultaneously tracking the membrane leakage. This will allow them to directly link the structural effects to the perturbation of the lipid membrane, which is an essential step.

So far, much of the understanding of AMPs stems from bacterial and vesicle assays that provide only indirect information of the molecular mechanisms or scattering experiments. The latter provide information on the membrane structure and AMP insertion, but do not show how this affects the membrane integrity and its ability to maintain the necessary electrochemical gradients.

Infectious diseases disproportionately affect developing countries and vulnerable populations. The development of safe and effective antibiotic alternatives that can overcome current resistant infections will also contribute to reduce such inequalities.

For further information about this HALRIC pilot project, please contact:

Vladimir Rosenov Koynarev
v.r.koynarev@kjemi.uio.no
University of Oslo