Staphylococcus aureus Binding Proteins for Prevention of Orthopaedic Implant-Related Infections

Abstract

Orthopaedic implant infections are an increasing problem and management commonly involves implant removal with serious consequences. Biofilm-forming staphylococci are the most common causative organisms, with Staphylococcus aureus being the most virulent and MRSA increasingly involved. Initial bacterial adhesion is a crucial event in biofilm formation and infection establishment. Directing host antibody against bacterial factors involved in adhesion and biofilm formation may significantly inhibit infection establishment on biomaterials. Two recombinant S. aureus-derived binding proteins (FnBP, IsdA) were investigated as potential vaccine antigens and resultant antibody was assessed to determine whether immune inhibition of bacteria-ligand binding can significantly impact on attachment to plasma-conditioned biomaterial surfaces, in the presence of other bacterial ligands. Adhesion of homologous and heterologous (clinical MRSA) S. aureus to plasma-conditioned steel was significantly reduced (~50% average reduction, p<0.0001) when pre-exposed to anti-rFnBP-A antiserum that was 50-fold more dilute than the actual titre from immunisation. Inhibition was related to ligand presence and not staphylococcal Protein A. Reduced adhesion was not observed with an FnBP-mutant strain, indicating specific inhibitory antibody involvement, and demonstrating the potential of rFnBP-A for prevention of S. aureus implantrelated infection. Adhesion-inhibitory activity was also observed with a purified IgG-fraction of rIsdA antiserum but this activity appeared to be masked by non-IsdA–related interactions when non-IgG-purified antiserum was assessed.