Antimicrobial resistance (AMR) is a global threat that has been thoroughly documented by WHO, EPHA, OECD and the CDC. Although the response to this threat needs to be multifaceted, one important focus is the discovery and development of efficacious and safe antibacterial compounds.
This HALRIC pilot project is a new cross border collaboration between the Universities in Copenhagen and Oslo. It will use Nuclear Magnetic Resonance (NMR) to better understand how promising peptides interact with components of bacterial and mammalian membranes and components of the blood plasma (e.g., the abundant serum albumin).
Antimicrobial peptides (AMPs) constitute a rich source of potential novel antibacterial agents that often target the membranes of bacteria and act so rapidly that AMR development is severely limited. Moreover, most pathogenic bacteria appear to lack preexisting resistance to these compounds.
Through previous international collaborations the researchers have developed an extensive library of AMPs based on bacterial type I toxins. Using established empirical design rules, these peptides have been modified to increase their solubility and their capacity to interact with charged bacterial membranes. One disadvantage of AMPs is their toxicity towards human cells, in molecular terms this means that the AMPs interact with human cell membranes in a disruptive manner that may lead to breaking down the cell (lysis).
NMR spectroscopy is a powerful technique that can probe interactions as well as structural changes of biomolecules like AMPs over a wide range of affinities and timescales, respectively.
The pilot project connects experts in peptide synthesis, structural biology, AMR, and microbiology. The peptides are designed, synthesized and purified by the researchers and where applicable clinical bacterial strains from Oslo University Hospital, Rikshospitalet will also be used.
NMR investigations will be performed in the infrastructure facility cOpenNMR at the University of Copenhagen. Alongside these studies, structural changes in the peptides when they bind to the membrane will be assessed using circular dichroism spectropolarimetry (CD).
