Interactions between staphylococci, heparin, heparin dependent growth factors and biomaterials

Abstract: Resident skin micro-organisms such as S. epidermidis and other coagulase-negative staphylococci (CoNS), are by far the most common causes of biomaterial-associated infections. These micro-organisms often exhibit surface adhesins that specifically bind serum and tissue proteins adsorbed to implanted biomaterials. The aim of this study was to extend our knowledge about such adhesins produced by CoNS. This thesis focuses on defining staphylococcal components interacting with sulphated glycosaminoglycans (GAGs) or heparin-binding growth factors. It was found that different CoNS strains (similar to S. aureus) interact with immobilised heparin, chondroitin and dextran sulphate. Moreover binding of the soluble heparin dependent growth factors, basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) was demonstrated and proposed to impair wound healing. Novel 17-kDa heparin binding proteins were isolated from both S. epidermidis strain RP 12 and S. haemolyticus strain SM131, and partially characterised. These proteins showed binding not only to heparin but also to bFGF and thrombospondin. As tested in several human cell lines, the heparin binding ligands appeared to be involved in the adherence of staphylococci to eucaryotic host cells. Finally, a new method, using collagen for immobilising antibiotics to heparinised biomaterials was developed, and the coating was found effective in reducing colonisation of staphylococci to biomaterials. It was concluded that improved combatment of biomaterial-associated infections will require detailed knowledge of the molecular events of colonisation, as well as effective antibiotic bonding of certain materials.