Molecular Basis of Adherence ofStaphylococcus aureusto Biomaterials

Abstract

This chapter focuses on the fibronectin-binding proteins (FnBPs) and fibrinogen-binding proteins (clumping factors, Clf) of Staphylococcus aureus. The role of the proteins in promoting bacterial adherence to immobilized ligand has been defined using site-specific adhesin-defective mutants that are compared with the parental strains in in vitro and in vivo models of foreign-body infection. The fnbA and fnbB genes of the laboratory strain 8325-4 have been inactivated by allelic replacement. This fnbAfhbB double mutant and the mutant carrying a multicopy plasmid that causes overexpression of FnBPA have allowed the role of FnBPs in promoting bacterial interactions with fibronectin to be defined. The fnbAfnbB mutant of strain 8325-4 was also defective in adherence to coverslips removed from subcutaneous chambers implanted in guinea pigs. The growth conditions used to prepare the bacterial cells for the adherence and virulence experiments would have prevented expression of the second clumping factor ClfB. The ClfA- mutant was defective in adherence to immobilized fibrinogen, while the complemented mutant adhered as well as the wild-type. The increasing incidence of multiple-antibiotic-resistant strains causing nosocomial infections has increased the urgency for alternative approaches to prevention and therapy. The problem is compounded by the recent emergence of methicillin-resistant S. aureus (MRSA) with intermediate sensitivity to vancomycin. In conclusion, there are several experimental vaccines that provide clear protection against S. aureus infections in animals. The challenge is to determine if any of these will protect human patients against nosocomial disease and, in particular, biomaterial-related infection.