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Targeting succinate metabolism to produce new chemotherapeutic agents

46 months
Approved budget:
Professor Gregory Cook
Dr Cara Adolph
Health issue:
Infectious disease
Proposal type:
NSFC Project
Lay summary
Antimicrobial resistance (AMR) threatens many of the achievements of modern medicine. Mycobacterium tuberculosis, a human pathogen that causes tuberculosis (TB), is unparalleled in its ability to infect humans, cause death, and develop resistance to all current classes of TB drugs. Cellular bioenergetics is an area showing promise for the development of new faster acting and highly potent drugs. The goal of our interdisciplinary research project is to develop a new class of narrow spectrum drugs that specifically target and inhibit the activity of Succinate dehydrogenase, an energy generating enzyme that is crucial for both replicating and non-replicating persistent forms of M. tuberculosis. Using an integrated combination of biochemistry, enzymology, microbiology and bioinformatics our project will drive innovation through the creation and characterisation of new lead candidates, suitable for pre-clinical development. These results will also advance bioenergetics as an area for drug development to target other serious AMR bacterial pathogens.