Uncovering the role of lipid renovation in bacteria-host interactions

Antimicrobial resistance is one of the most serious threats to humans in the 21st century. Understanding antimicrobial resistance mechanisms is pivotal for combating superbugs. Pathogens use many strategies to combat challenges by antimicrobial compounds to better adapt or survive antibiotic insults. This project aims to determine whether there is an overlooked dimension to antimicrobial resistance mechanisms, namely the remodelling of membrane lipids. Lipid remodelling is a process whereby bacteria selectively modify their membrane lipid composition in response to a particular environmental stimulus. Such remodelling potentially plays a role in dictating the permeability and selectivity of the outer membrane, mediating antimicrobial resistance. From a pathogen’s perspective, the lipid bilayer forms the first line of defence against the invasion of an antibiotic. We hypothesize that changes in membrane composition will result in selective recruitment of outer membrane proteins (such as efflux pumps), thus affecting antibiotic trafficking through the membrane. We recently discovered the central pathway responsible for bacterial lipid remodelling and demonstrated that lipid remodelling is common in diverse bacteria. It is present in many clinically important pathogens such as Burkholderia cenocepacia. This pathway is also essential for intracellular survival and plays a key role in subverting host autophagy and the innate immunity response. Using cutting-edge omics (transcriptomics/proteomics), advanced imaging (confocal) and cellular biology approaches (macrophages, autophagy biomarkers), this project aims to determine the link between lipid remodelling, antimicrobial resistance and intracellular survival using B. cenocepacia as the model organism.

References:
Shropshire et al. 2023 bioRxiv 2023.05. 30.542800.

Jones et al., 2021 ISME J https://doi.org/10.1038/s41396-021-01008-7.