Defining the factors that determine patient outcome following Staphylococcus aureus bacteraemia. (360G-Wellcome-212258_Z_18_Z)

Staphylococcus aureus is a major human pathogen, and of the types of infections it causes, bacteraemia is one of the most severe with mortality rates as high as 30%. With rates of bacteraemia increasing year on year, and antibiotic resistance making treatment more challenging, efforts are increasingly being focused on developing a vaccine. However, despite significant investment all attempts have failed, because we do not have a sufficiently detailed understanding of S. aureus’ pathogenicity. This proposal aims to address this deficit in understanding by applying a multi-stranded and multi-disciplinary research approach to large collections of clinical S. aureus isolates. Preliminary work modelling phenotypic, genomic and clinical data identified several novel bacterial features that significantly contribute to patient outcome following S. aureus bacteraemia. By adopting molecular, cellular, ‘omics and mathematical modelling approaches, this project will characterise these novel features and determine the contribution they make to the outcome of individual bacteraemic patients. In addition to transforming our understanding of S. aureus pathogenicity, the finding of this project has the potential to inform future S. aureus vaccine design approaches and identify bacterial targets for the development of novel therapeutic approaches.