Uncovering the role of lipid renovation in phage therapy

Antimicrobial resistance (AMR) is one of the most serious threats to humans in the 21stcentury. A promising approach for combating AMR is phage therapy. Bacteriophages are viruses that exclusively attack and lyse a bacterium, including bacterial pathogens. However, like all clinical procedures, phage therapy is subject to failure and the mechanisms underpinning unsuccessful phage therapy are not well established.
We hypothesize that the cell surface of bacterial pathogens plays a vital role in determiningthe success or failure of phage therapy in combating AMR. This project therefore aims to determine whether there is another, previously overlooked, dimension to combat antimicrobial resistance, namely the remodelling of membrane lipids. Lipid renovation is a process whereby bacteria selectively modify their membrane composition in response to a particular environmental stimulus, e.g.the availability of a specific nutrient. Such remodelling potentially plays a role in dictating the relative abundance of cell surface molecules such as membrane proteins, lipopolysaccharides both of which are known phage receptors.
We have previously isolated many bacteriophages targeting specific bacterial pathogens. Using cutting-edge lipidomics, transcriptomics and proteomics approaches, this project aims to provide a mechanistic understanding of the role of the cell surface in combating antimicrobial resistance.