London School of Hygiene & Tropical Medicine

The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Published studies have shown that this secretion pathway plays a very significant role in the ability of S. aureus to establish persistent infections. Our overall aim is to elucidate the mechanism of protein secretion by the S. aureus T7SS machinery and to identify secreted substrate proteins. Recently we have shown that some strains of S. aureus secrete a large nuclease toxin, EsaD, by this pathway. We have shown that strains secreting EsaD exhibit significant antibacterial killing activity against sensitive strains and that this most likely plays a role in colonisation. Very recently we have identified a further secreted substrate of the T7SS and we are currently elucidating its function.