Bismuth Based Antimicrobial Agents to Combat Antibiotic Resistance

Antimicrobial resistance (AMR) is a growing threat to human health worldwide. The proliferation of ‘superbugs’, bacteria which are resistant to almost all current antibiotics, will cause substantial global mortality due to untreatable infections in the near future1, so new antimicrobial drugs are urgently required. Bacteria are less likely to develop resistance to metal based antimicrobial agents, so the development of new metal containing antibiotics is an exciting possibility for overcoming the challenge of AMR. 

Bismuth complexes are known for their low toxicity and antimicrobial properties, and several have been clinically approved for the treatment of gastrointestinal Helicobacter pylori infections. More recently, it was found that combining a bismuth complex with an antibiotic helps to overcome drug-resistance, making previously drug resistant strains of Escherichia coli responsive to treatment.2  

The main class of clinically approved bismuth drugs are bismuth citrates. Despite their widespread clinical use, their chemical structure and behaviour are not well understood. One challenge is their low solubility, often leading to formulation as a colloidal suspension limited to oral treatments. 

This is an interdisciplinary project which aims to synthesise new, soluble complexes of Bismuth (III) and evaluate their structural and antimicrobial properties. You will target molecular drugs with well-defined bismuth coordination environments, and investigate their structure using crystallographic and spectroscopic techniques. You will undertake antimicrobial testing of the new complexes, both alone and in combination with other antibiotics, and develop an understanding of their structure-function relationships. Promising drug candidates will be tested in an in-vitro infection model and screened for mammalian toxicity. You will also aim to synthesise fluorescent bismuth complexes and use them to trace bismuth uptake in cell models. It was recently found that bismuth complexes inhibit the replication of the SARS-COV-2 virus which causes COVID-19,3 and anti-viral applications of any new bismuth drug candidates could be an exciting future step for this project. 

This project would suit a candidate with a degree in chemistry or chemical biology. Full training will be provided in all required techniques.