Biomaterial centered infections are increasingly caused by Staphylococcus epidermidis. Biomaterial surfaces that traverse the skin, such as sutures and catheters, are substrates for avid colonization by S. epidermidis. This organism has also become a principle pathogen in deep biomaterial infections. The adherence of S. epidermidis to surfaces and the persistence or virulence of this type of infection is related to a documented tendency to grow on substrates in biofilms within which its cells are protected from host defense factors by an exopolysaccharide matrix. Colonization of surfaces of transcutaneous and deep biomaterials is insidious because it does not immediately cause a clinical infection. In addition, clinicians have been reluctant to implicate this organism as a primary pathogen. S. epidermidis is autochthonous and is an initially non-invasive colonizer of surfaces of transcutaneous biomaterials; however, its sustained presence on biomaterials constitutes a reservoir from which it can emerge as an invasive pathogen. In Aim 1, we plan to examine the avidity of colonization of biomaterial substrates in an animal model using specific virulent and nonvirulent strains of S. epidermidis. In Aim 2, biochemical characterization of the exopolysaccharide of virulent encapsulated strains of S. epidermidis by gel chromatographic and compositional analysis will allow an understanding of the conversion of a virulent normal flora organism to a pathogen. In Aim 3, the adherence of S. epidermidis to biomaterials as they are prepared for surgical implantation, or as they have been modified (e.g., radio frequency glow discharge sterilized materials and antibiotic impregnated cement and synthetic vascular graft materials) will be quantified in an in vitro system. Antibiotic effectiveness against biofilm protected colonies on substrates will also be evaluated. Relevant surface factors of the biomaterials such as glycoproteinaceous conditioning films, surface energy and hydrophobicity will be considered. In Aim 4, purified exopolysaccharide of S. epidermidis will be tested for its influence on the function of macrophages including phagocytosis and bacterial killing. This comprehensive study will be conducted by three experienced investigators having combined expertise in surgical infections, biochemistry, microbiology, and immunology, and is of major importance because it will elucidate the critical factors responsible for the increasing and costly problem of biomaterial-associated infections.