Defining strategies to promote immunity to multi-drug resistant Staphylococcus aureus.

Staphylococcus aureus is a highly successful pathogen that can circumvent many aspects of immunity. White blood cells, including neutrophils, are a critical defence against infection and yet S. aureus is able to render them ineffective. S. aureus does this in multiple ways and one is by inducing neutrophil lysis. This catastrophic form of cell death results in significant bystander tissue injury and inflammation. S. aureus can also survive inside neutrophils, evading the anti-microbial immune defences and eventually bursting open the cell and becoming free to cause infection elsewhere.

Whilst the development of novel antimicrobial compounds is an attractive strategy, the history of antimicrobial resistance of S. aureus tells us that any therapeutic benefits are likely to transient. We believe instead that therapeutically manipulating the innate immune response to S. aureus has significant appeal, not only because of the rapid engagement of innate immunity during infection but also because of the reduced potential for bacterial resistance.

This project will use microbiological, pharmacological and microscopy techniques to determine how S. aureus disables the immune response so effectively. Neutrophils will be isolated from the blood of healthy individuals as well as from patients who are prone to infections. The student will screen drug libraries to identify compounds that improve killing of S. aureus by human neutrophils. Not only will this reveal new mechanisms of immune cell function during infection, but may also uncover new therapeutics for treating S. aureus infections in the future.

The student will join a vibrant and friendly research team of postgraduate researchers. Dr Prince’s group is situated within the Department of Infection Immunity and Cardiovascular Disease in the Medical School.
https://www.sheffield.ac.uk/medicine/iicd
https://www.sheffield.ac.uk/iicd/profiles/prince

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