Unlocking a new generation of antimicrobial resistance targets by high-throughput lipidomics drug discovery

Escherichia coli is the leading cause of death associated with drug-resistant bacterial infections and is one of the World Health Organisation's highest priority pathogens for which new treatments are desperately needed. Focussing on the mechanism of assembly of the outer membrane of Escherichia coli and capitalising on the new drug discovery hub at Imperial, this project will develop and implement a high-throughput mass-spectrometry-based approach to identify new compounds that target the Gram-negative cell envelope via novel modes of action. Taking an interdisciplinary approach to drug discovery, hits will be optimised for potency, spectrum of activity, and therapeutic index. Hits with the best profiles will be subjected to target identification approaches which employ lipidomic, genetic, chemical biology and proteomic approaches, with the ultimate goal of developing novel antibiotics for use in the clinic.