Uncovering the role of lipid remodelling in phage therapy

Phage therapy is a promising treatment for bacterial infections, particularly those caused by antibiotic resistant bacteria. Bacteriophages (or phages) are viruses which can infect and kill bacteria, thereby eliminating infection. But before these can be widely used as a therapy, more research needs to be done into what causes phage therapy to be successful or not.
This project will investigate the role of the bacterial cell surface in phage therapy. In response to environmental factors such as nutrient levels, bacteria may alter the lipid makeup of their cell membranes. This may have an impact on membrane proteins or lipopolysaccharide in Gram-negative bacteria. These are both known phage receptors, and therefore it is possible that lipid remodelling could influence the efficacy of phage therapy. Bacteria that exist in in vitro environments are likely to have a different lipid makeup than those in the body, so it is important to understand whether this will affect phage binding and infection.
The bacteria that will be used to study this are lung pathogens such as Pseudomonas aeruginosa, which is prevalent in people with cystic fibrosis. It also has high intrinsic resistance to certain antibiotics, and therefore important pathogens to find alternative treatment for. We will systematically investigate the genes involved in membrane modification in response to environmental cues and the knock-on consequence on phage infection dynamics.