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Novel antimicrobial agents for combatting infectious diseases

Supervisor: Professor Peter Sadler (Chemistry)

Resistance to treatment of infections by current antibiotics is now a global health problem. Our research shows that transition metal complexes with specific targeting ligands have potential to provide new generations of antibiotics with novel mechanisms of action. The key to advancing the design and use of such complexes is identification of their target sites and the biochemical pathways which they inhibit. This is a major challenge which will require application of cutting-edge biochemical and chemical analytical methods.

Suitable metal complexes containing targeting ligands, especially Chinese natural products, will be designed, synthesised and characterised by HPLC, UV-vis, NMR, MS and x-ray crystallography. The use of nanoparticles will be explored as delivery systems. They will be screened for antimicrobial activity, including the ESKAPE panel development of resistant mutants, and cell uptake determined by ICP-OES and ICP-MS. Ability to prevent biofilm formation and eradication of ESKAPE bacteria in mature biofilms grown in high-validity models of wound and respiratory biofilm infection will be studied. Cellular targets will be identified by fractionation, MS, and metallomics methods, including optical, electron (TEM) and x-ray imaging for elemental mapping and ligand distribution (including cryo-fixation of cells to preserve their near-native states during analysis), and NMR spectroscopy of cell extracts.

Start date: 26 September 2022

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