Discovering new antimicrobials against multi-resistant microorganisms (collaboration with MedImmune)

The Drug Discovery Technology Unit has had extensive experience in the discovery of antimicrobial peptides from its phylomer libraries. Some of these peptides have activity on multiresistant isolates of Acinetobacter baumanii, an important cause of hospital acquired infections of burns patients.

We have also screened Phylomer libraries to identify and characterize antimicrobial peptides against the related pathogen Pseudomonas aeruginosa, which is involved in hospital-acquired catheter and burns infections as well as lung infection, particularly in children suffering from cystic fibrosis.

The group has investigated the biophysical properties of antimicrobial Phylomer peptides by a technique known as circular dichroism. These studies measure the extent of formation of the alpha helix structure in model membranes incorporating various phospholipid mixtures which mimicking different types of bacteria or mammalian cells.

These studies found good agreement between prediction in silico and biophysical measurements. We also were able to optimize antimicrobial Phylomer peptides - reduced length to approximately 20 amino acids and improving the activity (MIC) to the high nanomolar range.

Recent studies have explored the potential synergy between clinical antibiotics and antimicrobial Phylomer peptides and found at least one potent combination. We have found a number of peptides with antimicrobial activity against the nosocomial infective agent Pseudomonas. aeruginosa.

We have established a control panel of recently published, highly active natural antimicrobial peptides and compared them with antimicrobial Phylomer peptides under different salt conditions (different broths), and have identified Phylomer derivatives which are more active than a potent antimicrobial peptide known as Tachyplesin which is isolated from the horse-shoe crab.

Tatjana Heinrich, Richard Hopkins