Overcoming antimicrobial resistance to tetracycline antibiotics
LEAD SUPERVISOR: Professor Chris Schofield, Department of Chemistry
Co-supervisor: Professor Fernanda Duarte, Department of Chemistry
Commercial partner: Ineos / Ineos Oxford `Institute for Antimicrobial Resistance (IOI), Oxford
Tetracycline type antibacterials are a mainstay of modern medicine and are also widely used in farming. However, their use is increasingly compromised by resistance, including by the Tet-X enzymes which are the mechanistically interesting flavin dependent monoxygenases. Whilst work with the beta-lactam antibiotics, such as the pencillins and cephalosporins, has shown the clinical utility of protecting them from enzyme mediated resistance by use of an inhibitor in a combination therapies (e.g. Augmentin = penicillin + clavulanic acid, a beta-lactamase inhibitor), this approach is largely unexplored for other antibacterial classes, such as tetracyclines, including new generation compounds such as tigecycline. The project will aim to address this by enabling the development of inhibitors of the Tet-X enzymes. The project will involve assay development, structural (including high-throughput and time resolved methods) and mechanistic studies, and inhibitor design / screening / synthesis, with the precise focus depending on the interests of the particular student.
Apply using course: DPhil in Organic Chemistry
January 2023 update:
Applications for this iCASE project (for October 2023 entry) are no longer accepted.