Staphylococcal fibronectin-binding proteins

This thesis describes a series of studies examining the fibronectin-binding proteins (FnBPs) of the pathogenic bacteria Staphylococcus aureus and Staphylococcus schleiferi. The first two results chapters explore the role of FnBPs in the interaction between S. aureus and human endothelial cells in vitro. The impetus for studying this area was the likely importance of this interaction in vivo during the process of bacterial seeding from the bloodstream to distant sites, a common accompaniment to bacteraemia and invasive disease. Having demonstrated a central role for FnBPs in adherence to, and invasion of endothelial cells, the third results chapter describes phenotypic and genotypic variation in fnb genes and the proteins they encode in a large population of ciinical S. aureus isolates. The fourth results chapter examines whether proteases, and in particular serine (V8) protease, influence S. aureus FnBP function, potentially modelling the bacterial cell surface and controlling the presence or absence of a functional adhesin. The fifth results chapter demonstrates that S. schleiferi, a coagulase-negative staphylococcus and a nosocomial pathogen, expresses a FnBP. In the final results chapter, the presence of fnbA encoding S. aureus FnBPA is compared between isolates associated with carriage and invasive disease, together with 32 other bacterial factors. The aims of this study were to identify virulence-associated genes (one of which was fnbA); to assess the cumulative effect of viruience-associated genes on virulence; and to identify gene combinations and determine if some combinations have a greater pathogenic potential than others