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 disease1. The Ess machinery comprises six core components1, four of which are membrane proteins, one is cytoplasmic and one is extracellular2. Little is known about how the core machinery is organized, and how it is regulated. One of the aims of this project will be to investigate the post-translational regulation of the Type VII secretion system.
Analysis of 153 S. aureus genome sequences revealed that the ess locus falls into four distinct clusters that each encode different sets of secreted substrate proteins3. The identity and functions of most of these substrate proteins is completely unknown. The second aim of the project will be to identify and characterize candidate substrates and elucidate their roles in virulence.
Training provided – the student will receive training in microbiology techniques including S. aureus genetics, protein biochemistry and protein interaction studies, and interaction of bacteria with host cells.
1Kneuper, H., et al. (2014) Molecular microbiology 93, 928-943.
2Jager, F., et al. (2016) FEBS letters 590, 349-357.
3Warne, B., et al. (2016) BMC genomics 17, 222.