Uncovering pathogenic mechanisms in methicillin resistant Staphylococcus aureus

Methicillin resistant Staphylococcus aureus (MRSA) causes infections in humans that are extremely challenging to treat. S. aureus possesses a vast repertoire of surface-located and secreted proteins that mediate interactions with the host and underpin its versatility as a pathogen. In particular, cell wall-anchored (CWA) proteins are regarded as being crucial during both colonisation and infection as they promote bacterial adhesion, invasion of host cells, immune evasion and biofilm formation. While the interaction of CWA proteins with host factors has been studied in detail with bacteria cultured under standard laboratory conditions, we know far less about how conditions experienced in the host influence CWA protein expression and activity.
Host factors interacting with the bacterial cell surface influence pathogen biology by damaging the bacterial cell, inhibiting bacterial attachment to host structures, or enhancing uptake by immune cells. Similarly, microbes that occupy the same ecological niche, such as the nares and the skin, can interfere with S. aureus colonisation and infection. This can be via inhibition of S. aureus growth or adhesion, disruption of biofilm formation, and interference with quorum sensing. The aim of this project is to establish how the activity of CWA proteins is modulated in complex environments that mimic those at colonisation and infection sites, and how this influences the S. aureus-host interaction