Antimicrobial resistance (AMR) is one of the biggest health threats that mankind currently faces. The emergence of multidrug-resistant, highly virulent strains of bacteria is a particularly grave threat.
New drugs with novel mechanisms of action are urgently needed to defeat AMR infections, as well as far-reaching public engagement programmes to combat misconceptions and change the way antibiotics are (mis)used.
One exciting possibility for the development of next-generation antibiotics is cyclic antimicrobial peptides. It is difficult for bacteria to develop resistance to these cyclic antimicrobial peptides, because they target specific lipids only found in bacterial membranes. However, understanding how these peptides selectively recognise and interact with target lipids at the molecular level in complex membrane environments is very challenging, and thus they cannot yet be developed as antibiotics without serious side effects.
In her EPSRC Open Plus Fellowship, Professor Alethea Tabor (UCL Chemistry) will develop new techniques and approaches to investigate how complex cyclic and polycyclic antimicrobial peptides selectively interact with their target lipids at the molecular level.
Designing and synthesising analogues of these peptides incorporating photocrosslinking chemical probes or specific NMR labels will enable the team to take “snapshots” of the peptide-lipid interactions in the membrane.
Professor Tabor says: “We will combine this with NMR and model membrane studies to determine how the peptides behave in membrane environments. This structural data will enable us to develop new antimicrobial drug leads active against multidrug-resistant bacteria.
“Most people have little understanding of the causes and impact of AMR and of how their behaviours and choices contribute to this “hidden pandemic”. There have been very few attempts to engage with the most deprived communities in England, yet these are the worst affected by antibiotic-resistant infections.
In the ‘Plus’ component of my Fellowship, I will work with young people in marginalised communities in London, providing training in media techniques and collaborating with them to produce visual art to communicate the threat of AMR to their communities in their own words.”
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- Professor Alethea Tabor