This is a competitive renewal application requesting funds to continue our studies of Staphylococcus epidermidis, biomaterials and pathogenicity. Adherent strains of S. epidermidis are the most frequent cause of biomaterial-induced infections. It appears that the capacity of coagulase- negative staphylococci to adhere to the surfaces of biomaterials represents an important virulence attribute of these normal flora organisms. The significant features of biomaterial-centered infections are: (1) adherent colonization of surfaces, (2) production of extracapsular polysaccharides, and (3) persistence of infection due to impaired host defense mechanisms. Adhesion to surfaces is believed to depend in part on interactions involving extracapsular polysaccharides, matrix proteins, and the specific atomic geometry and electronic state of the biomaterial surface. Our preliminary studies indicate that attachment of S. epidermidis to biomaterial surfaces most likely involves surface polysaccharides and adhesive host proteins like fibronectin. In the case of titanium alloy, elemental surface segregations of vanadium also appear to favor adherence. In addition, we have observed that macrophages exhibit an impaired phorbol myristate acetate (PMA) -elicited oxidative burst after interaction with polymethylmethacrylate (PMMA). Macrophages exposed to PMMA also failed to respond to macrophage activation factor, which suggests that they are defective in terms of becoming primed. These deficits could explain the impaired killing of S. epidermidis at the biomaterial-tissue interface.
In Aim 1, our preliminary data will be further explored by continuing our isolation, extraction, and purification studies of extracapsular polysaccharides of S. epidermidis RP-12 strain;
in Aim 2, we will identify the dominant fraction(s) involved in primary binding and select the smallest oligosaccharide component which will competitively inhibit the binding of S. epidermidis to biomaterials or conditioning proteins.
In Aim 3. the role of biomaterial (Ti6A14V) surface features (eg elemental segregations) will be evaluated as binding sites for S. epidermidis and for S. epidermidis exopolysaccharide fractions using energy dispersive x-ray analysis correlated with electron microscopy.
In Aim 4, the role of biomaterials (Ti6A14V), polymethylmethacrylate, and polyurethane in phagocyte impairment will be investigated by determinations of oxidative metabolism and killing capacity of macrophages for S. epidermidis in the presence of selected biomaterials.
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