Molecular interactions and protein stability in the accessory gene regulator quorum sensing system of Staphylococcus aureus

Staphylococcus aureus is a normal skin commensal and an opportunistic pathogen that presents serious threat to healthcare. It is the causative agent of septicaemia and bacteriaemia and is implicated in significant morbidity and mortality in hospital patients, particularly resistant strains such as MRSA. The accessory gene regulator, agr, system encodes bacterial communications that modulate the expression of virulence factors and bacterial population dynamics playing a major role in patient quality of life and as determinant of clinical outcome. We investigate drug targets on the agr pathway using individual pathway members and a set of lead compounds with demonstrated activity in regulating the agr system. We propose to use SANS at ISIS to observe the complex formation between protein partners in the agr cascade and the role of inhibitors on their assembly and stability.