Defining the critical host - pathogen interactions that affect patient outcome during Staphylococcus aureus bacteraemia.

Staphylococcus aureus is a major human pathogen, with bacteraemia (SAB) causing the most severe infection outcome, associated with mortality rates of 20-30%. Despite advances in modern medicine, the incidence of SAB is increasing year-on-year, while the threat posed by antimicrobial-resistant infections necessitates immediate adoption of disruptive approaches to reduce global disease burden. To-date, research has focussed on either host or pathogen factors underlying disease progression. However, it is clear that these must be considered in parallel if we are to develop new intervention and therapeutic strategies to tackle the significant health problem SAB represents. Through the unique opportunity to access an unprecedented global collection of >7000 isolates from the ongoing, international SNAP Trial, this cross-disciplinary project will utilise in vitro and in vivo discovery-based approaches in combination with human clinical data to build the first detailed description of key bacteria-host interactions and processes underlying establishment and severity of SAB. Newly identified host and pathogen biomarkers predictive of patient outcome will be leveraged to devise risk stratification approaches and identify key intervention points to inform treatment guidelines. These will be implemented and validated through the SNAP trial platform to reduce the burden of SAB for patients and healthcare settings.