Binding of plasma proteins by Staphylococcus epidermidis: characterisation of protein-protein interactions

Detta är en avhandling från Dai-Qing Li, MMDI, Sölvegatan 23, 223 62 Lund, Sweden

Sammanfattning: Coagulase-negative staphylococci (CoNS), in particular, Staphylococcus epidermidis, have emerged as major nosocomial pathogens associated with infections of implanted medical devices. These organisms, which are among the most prevalent bacteria of the human skin and mucous membrane microflora, gain access to the surface of the implant at the insertion. However, the subsequent infection may erupt up to a year later or more. It is currently believed that two steps are involved in the infections: 1) primary bacterial adhesion to the biomaterial surface, which has been covered by host factors; 2) bacterial cell accumulation and biofilm formation. Specific interaction between bacteria and host factors, e.g. adsorbed plasma proteins on a biomaterial surface, has long been regarded as a key step in the pathogenesis of S. epidermidis infections. Our studies deal with the binding of vitronectin (Vn), clusterin (Clu), recombinant von Willebrand factor (rvWF) and thrombospondin (TSP) by S. epidermidis. S. epidermidis binds soluble forms of Clu, rvWF and TSP specifically. Bacterial binding to immobilised Vn, rvWF and TSP was higher than the positive control Staphylococcus aureus strains. Although S. epidermidis might not utilise immobilised Clu as an attachment site on biomaterial, Clu binding by S. epidermidis can abate the inhibitory effects of Clu on membrane attack complex (MAC) formation. Therefore, the binding may contribute to endothelial cell injury and inflammation developing around colonised implants. In addition, two Vn-binding proteins (21 and 52 kDa) of S. epidermidis strain BD5703, isolated from cerebrospinal fluid (CSF) shunt infection, were purified and identified. Glucosaminidase (the 52 kDa protein) is the major Vn-binding protein of BD5703. Extracellular cysteine protease (the 21 kDa protein) may also be important in the pathogenesis of CSF shunt infections. With increased bacterial resistance to traditional antibiotics, vaccination is likely to become more important to combat staphylococcal infections. In a mouse sepsis model, immunisation with cell surface extract of S. aureus strain Phillips stimulated the host to produce protective antibodies. This is promising for further investigations.

  Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.