BIOMATERIAL SUBSTRATES - S. EPIDERMIDIS & PATHOGENICITY

以生物材料为中心的感染越来越多地由葡萄球菌引起 表皮肌。穿过皮肤的生物材料表面，如缝合线 和导管，是表皮葡萄球菌贪婪定植的底物。 这种微生物也已成为深部生物材料的主要病原体 感染。表皮葡萄球菌对表面的粘附性 这种类型的感染的持久性或毒力与 有记录的在生物膜中的基质上生长的趋势，其中 胞外多糖保护细胞免受宿主防御因子的影响 矩阵。经皮和深部生物材料的表面定植 是潜伏的，因为它不会立即引起临床感染。 此外，临床医生一直不愿将这种微生物作为一种 主要病原体。表皮葡萄球菌是原生的，最初是一种 经皮生物材料表面的非侵入性定植剂；然而， 它在生物材料上的持续存在构成了一个储存库， 它可以作为一种侵袭性病原体出现。在目标1中，我们计划研究 生物材料基质在动物模型中的定植亲和力 表皮葡萄球菌的特定毒力和非毒力菌株。在目标2中， 强毒菌株胞外多糖的生化特性 凝胶层析包埋表皮葡萄球菌的研究 成分分析将允许理解一个 对病原体有毒力的正常菌群生物。在目标3中，坚持 表皮葡萄球菌对生物材料的依赖，因为它们正在准备手术 植入，或当它们被修改时(例如，射频辉光 排放灭菌材料和抗生素浸渍的水泥和 合成血管移植材料)将在体外进行量化 系统。抗生素对生物被膜保护菌落的效果 还将对基质进行评估。相关的表面因素 生物材料，如糖蛋白调节膜，表面能 疏水性将被考虑。在目标4中，纯净 将测试表皮葡萄球菌胞外多糖对细胞生长的影响 巨噬细胞的功能包括吞噬和杀菌。这 综合研究将由三名经验丰富的调查人员进行 在外科感染、生物化学、 微生物学和免疫学，是非常重要的，因为它将 阐明导致成本增加和成本增加的关键因素 生物材料相关感染问题。

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.