Structural and functional analysis of a Staphylococcus aureus immune evasion protein

The human pathogen Staphylococcus aureus utilises an immune evasion protein (Sbi) to escape elimination by activating the innate immune system. This immune evasion protein forms a supra-molecular protein complex comprised of Sbi, a fragment (C3b) of the complement component C3 and complement regulators Factor H or Factor H related protein 1 (FHR-1), which results in the futile consumption of a central component of the complement system (C3). The van den Elsen lab have previously produced low-resolution structures of this supra-molecular complex, using small-angle X-ray scattering (SAXS).

This project aims to gain a detailed understanding of the structure of this supra-molecular complex by utilising structural analysis methods, including electron cryo-microscopy (Cryo-EM) in combination with X-ray crystallographic studies of the complex and its individual components. Furthermore, mutational studies of the interfaces between the components of this complex will provide information about potential ways of interfering with complex formation.

A detailed understanding of the structure and formation of this complex is crucial for understanding how Staphylococcus aureus can evade our immune system, which will allow the development of effective antibiotics to treat this pathogen. Additionally, the complexes complement consumption ability may provide an effective method for treating inflammatory diseases (such as Rheumatoid Arthritis and Multiple Sclerosis) that are caused by an overactive immune system.