A fibrinogen-binding protein from Staphylococcus epidermidis

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Immunology, Microbiology, Pathology and Infectious Diseases

Sammanfattning: Staphylococcus epidermidis, a coagulase negative staphylococci (CoNS), is a major component of human flora. It is one of the leading pathogens of nosocomial infections, particularly associated with foreign body infections. The increasing rate of nosocomial epidemics caused by multiresistant staphylococci requires a better understanding of the pathogenesis of staphylococcal infections. Two steps are involved in bacterial infections on the implants: initial colonization and cell accumulation. Adherence of S.epidermidis to fibrinogen deposited on the surfaces of implants is important for the development of foreign body infections. We here report our studies on a fibrinogen-binding protein from S.epidermidis. A gene (fbe) encoding a fibrinogen-binding protein from S.epidermidis (Fbe) is identified by shotgun phage display. As a member of the SD-multigene family in staphylococci, Fbe shares some similar constructions with other surface proteins of staphylococci. Although most strains of S.epidermidis contain part of fbe, the binding of S.epidermidis to immobilized Fg in vitro shows a heterogeneous pattern, suggesting that other factors may influence the surface exposure of Fbe. The interactions between rFbe and Fg have been extensively studied. The Fg binding responding domain is located on a 331-amino-acid sequence of the A- region of Fbe. rFbe binds to the P chains of Fg and this interaction can be accelerated by calcium. Such an interaction between Fbe and Fg may promote the binding of S.epidermidis to Fg in physiological environments. In the inhibition study, the binding between Fg and S.epidermidis can be blocked by rFbe and its antibodies. The antibodies against rFbe efficiently block the binding between S.epidermidis and surface-bound Fg. The inhibition of adherence to subcutaneously implanted catheters from rats and peripheral venous catheters from patients is less efficient than to Fg-coated ones. This suggests that other components adsorbed on the implant surfaces may also be involved. In the study on the isogenic mutant lacking fbe, lower adherence to Fg exposed surfaces is found fbeisogenic mutant in comparison to its wild type. Thus, Fbe may be a major adhesin to Fg in S.epidermidis. The remained adherence of the mutant to explants suggests that adhesins to other host components may strengthen the interaction between bacteria and the implants. Furthermore, the strategies to prevent and treat S.epidermidis-associated foreign body infections are discussed, including infection controls, new antibiotics, new biomaterials, and immunoglobulin therapy. With more knowledge of the pathogenesis, opsonophagocytic properties of antibodies, and the role of cytokines in S.epidermidis-associated infections, an immunoglobulin therapy targeting Fbe may become a promising strategy in prophylaxis and therapy.

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