A team of Irish and UK researchers including a Professor from the University of Exeter have been awarded £4.2 million of funding from Wellcome to investigate the leading global cause of fatal bloodstream infection.

Bloodstream infections are a major cause of illness and death worldwide. The bacterium Staphylococcus aureus is the leading global cause of these fatal bloodstream infections, with antimicrobial resistant (AMR) strains such as methicillin resistant S. aureus (MRSA) compounding what is considered a major clinical problem.

Despite advances in modern medicine, the incidences of bloodstream infection are increasing year-on-year, and scientists and doctors have no definitive understanding of why this is. Furthermore, these bacteria are present in the microbiome of approximately one third of the human population, and it is well established that those colonised by S. aureus are at higher risk of infection.

The team is led by Professor Ruth Massey at the University College Cork, working with  together with Professor Mario Recker from the University of Exeter, Professor Rachel McLoughlin from Trinity College Dublin, and researchers from the University of Bristol. The funding will allow the team to examine how this bacteria cause damage to human tissue and evade the immune system.

Building on their past research they will build the first detailed description of the key bacteria-host interactions and processes that control the establishment and severity of S. aureus bloodstream infection, with a view to identifying key intervention points to inform treatment guidelines and ultimately reduce the burden of S. aureus infection for patients and healthcare settings. The project will advance critical understanding of how this notorious human pathogen causes disease.

Professor Massey, Principal Investigator at APC Microbiome Ireland SFI Research Centre, and a Senior Academic Leadership Initiative Professor at University College Cork’s School of Microbiology, said: “We are in a true race against time to understand the root causes of S. aureus bloodstream infections, where the bacteria currently have the upper hand.

“We believe that alongside other patient and bacterial factors, the role of the microbiome, with respect to both the presence of the bacteria with the microbiome, and how the microbiome trains our immune system to respond to infections will be key to tackling this major global clinical problem. This funding will allow us to shine a light on this poorly understood problem with a view to developing strategies and new therapies to reduce infection rates and patient suffering.”

Professor McLoughlin, from Trinity’s School of Biochemistry and Immunology, is based in the Trinity Biomedical Sciences Institute. She said: “The trial creates a once-in-a-lifetime opportunity to capture and define the full and varied picture of how this major human pathogen causes disease, and we are very grateful to Wellcome for enabling us to capitalise on this opportunity. This study has the potential to be a game changer for infectious disease research because it represents the first attempt to build a fully integrated model of an infectious disease incorporating the host, the pathogen and the treatment.

This project will provide an entirely new understanding of how the notorious pathogen Staphylococcus aureus causes disease. In doing so it will lead us to identify biomarkers for rapid patient risk stratification in clinical settings and identify new avenues for therapeutic development – ultimately, improving patient care and relieving the burden of this disease on a global level.”

Professor Mario Recker from the University of Exeter will oversee the data analysis and modelling part of the project. He said: “The wealth of data generated through this multinational project will provide unprecedented details of the interactions between the bacteria and the human host, which will ultimately help us to predict infection outcomes and thus guide patient-based treatment options.”