Staphylococcus aureus invasion of host cells: the role of multiple fibronectin-binding sites, integrin-clustering and caveolae in invasion. (360G-Wellcome-079588_Z_06_Z)

Staphylococcus aureus is a major human pathogen. With strains emerging worldwide that are resistant to all antibiotics, it is imperative that novel strategies are developed to combat infections. The ability of any pathogen to attach to its host is critical to a successful infectious cycle. S. aureus is well equipped for this, expressing several proteins that allow it to attach to and invade host cells. The fibronectin binding-protein A (FnBPA) is one of S. aureus' major adhesins that also facilitates invasion of host cells. This study will determine the molecular interactions that occur between FnBPA and host cells to facilitate invasion by this pathogen. Key Goals: (1) Determine the role of multiple binding sites within the FnBPA protein. (2) Detect whether integrin clustering occurs after the bacteria and host cells interact. (3) Observe whether these integrin clusters migrate towards caveolae on the host cell surface. (4) Determine whether invasion is dependent upon the presence of caveolae on the host cell. Our hypotheses will be tested from both the bacterial and host cell perspective, using molecular and cellular biological techniques with a view to identifying novel strategies for the prevention and treatment of invasive diseases caused by this pathogen.