About the Project
Tackling AMR requires the development of new antibiotics, particularly those that function by targeting different bacterial mechanisms than current antibiotics. These new medicines will circumvent current resistant mechanisms being used by drug resistant bacteria. Also, new medicines which reverse resistance to current antibiotics should be developed, allowing for improved effectiveness of current antibiotics. This project will explore a novel strategy against this problem. A common mechanism that bacteria deploy to resist antibiotics is the secretion of beta-lactamases. Our group has considerable expertise and resources focussed on the analysis of bacterial protein secretion – the Sec-machinery. We aim to exploit this knowledge towards the specific analysis of the transport of the beta-lactamases, which are exported via this route. The project will involve the development of in vivo and in vitro secretion assays that report on the transport of a range of beta-lactamases. Once established we will undertake a comprehensive analysis of the mechanism of this process and the specific requirements for beta-lactamase secretion.
The project is multi-disciplinary, involving the application of a spectrum of technologies ranging from microbiological to functional reconstitution of membrane systems for biochemical and biophysical analysis – for an excellent training opportunity.
The development of drugs against the secretion of beta-lactamases would be particularly valuable as they would act against a wide range of resistant mechanisms and thus re-potentiate those antibiotics that have been rendered impotent by emergent strains. We already have a collaboration with the Dundee Drug Discovery unit for the deployment of high throughput screens against the general secretion process. Therefore, this studentship presents an excellent opportunity to target the features of the transport machinery pertinent to AMR.
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