*4 Year WT PhD Programme* Roles in virulence and antibacterial competition of the Staphylococcus aureus Type VII secretion system.

The Gram-positive bacterium, Staphylococcus aureus, is a major pathogen of humans and animals. In humans it is a leading cause of community and hospital acquired infections and is associated with life-threatening diseases such as pneumonia, meningitis, endocarditis, toxic shock syndrome, bacteraemia, and sepsis. The organism is notorious for its ability to develop resistance to antibiotics, and is one of the seven bacterial species highlighted by the World Health Organisation as being of critical antimicrobial resistance concern. Bacterial virulence factors that directly interact with the host must be secreted from the bacterial cytoplasm where they are made. Protein secretion systems are therefore critical to the success of all bacterial pathogens.

We and others have shown that the Ess (Type VII) protein secretion system plays a critical role in the ability of S. aureus to cause disease. Very recently we have also identified a previously unexpected role for the secretion system in killing bacterial competitors. The identity and functions of the secreted substrates that are required for anti-bacterial and anti-eukaryotic activity of the S. aureus Ess system are almost completely unknown. The main aims of this project will be to identify secretion substrates and elucidate their functions. The types of approaches that will be used include proteomics, mammalian cell culture, protein biochemistry and structural biology.