Researchers analysed data from multiple studies and identified nearly 4,000 genes linked to the immune response to Staphylococcus aureus. They highlighted 14 promising treatment targets, some already associated with existing drugs. These findings could guide the development of immune-based therapies to support or replace antibiotics in treating serious S. aureus infections. The bacteria Staphylococcus aureus (S. aureus) is a common cause of serious infections which can be difficult to treat with conventional antibiotics. A new approach to treatment, aimed at improving our own body’s immune response to S. aureus, could be a useful addition or alternative to conventional antibiotics. However, due to the complexity of the immune system, it is very difficult to identify specific elements of the immune response to study as targets for potential treatments.IRR researcher Dr Clark Russell (ECAT Clinical Lecturer in the Dockrell Lab), together with colleagues at The University of Edinburgh and Leiden University, gathered and analysed a wide range of previous studies that looked at how cells, animals and people respond to S. aureus. They focussed only on studies that could look at nearly every gene in the body. Using a computer method called "meta-analysis by information content", they combined the results to create a single list of genes involved in the response to this bacterium. These genes were ranked by how strong the evidence was for each one. Before conducting the analysis, we made a list of 23 potential targets for treatments that might boost the immune response against S. aureus. Remarkably, 14 of these were prioritised by the analysis, therefore identifying multiple possible targets for a new approach to treating S. aureus disease. Many of these could be targeted using drugs which are already licenced for other purposes. Dr Clark Russell ECAT Clinical Lecturer and paper’s first author The study pinpointed 3,867 genes that seem to play a role in responding to S. aureus. Many of these are linked to white blood cells (immune cells which fight infections) and platelets (involved in blood clotting). In addition to known anti-bacterial defences, we found strong evidence for lesser-known mechanisms that help protect against S. aureus. These include programmed cell death (apoptosis), a cellular clean-up mechanism (autophagy), iron metabolism, and blood clotting processes. The researchers also identified “hub” genes - key genes that interact with many others and may play a central role regulating the immune response.The researchers will conduct experiments using human white blood cells and animal models of S. aureus infection to confirm specific results and investigate potential treatments identified by the analysis. Ultimately, they hope their findings will contribute to evidence-based selection of immune-based treatments to study in clinical trials of S. aureus infections. Read the full paper in The Journal of Infectious DiseasesBaillie-Gifford Pandemic Science Hub, Institute for Regeneration and RepairRoslin InstituteLeiden University Center for Infectious Diseases Tags CIR Publication date 16 Jun, 2025
