BIOMATERIAL SUBSTRATES--S. EPIDERMIDIS & PATHOGENICITY

生物材料基材--S。

• 批准号: 3289402
• 负责人: ANTHONY G. GRISTINA
• 金额: $ 16.4万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3289402
• 关键词: Staphylococcus epidermidis; antibiotics; bacterial disease; biomaterials; laboratory rabbit; phagocytosis; tissue /cell culture; virulence

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.

以生物材料为中心的感染越来越多地由葡萄球菌引起 表皮的 穿过皮肤的生物材料表面，如缝线 和导管，是S.表皮 这种生物也已成为深部生物材料中的主要病原体 感染. S.表皮至表面， 这种类型的感染的持续性或毒力与 有记录表明，在生物膜中的基质上生长的趋势， 细胞通过一种胞外多糖来保护免受宿主防御因子的影响 矩阵 经皮和深部生物材料表面的定植 是潜伏性的，因为它不会立即引起临床感染。 此外，临床医生一直不愿意牵连这种生物体作为一个 主要病原体 S. epidermidis是原生的， 经皮生物材料表面的非侵入性定殖器;然而， 它在生物材料上的持续存在构成了一个水库， 它可以作为入侵性病原体出现。 在目标1中，我们计划检查 在动物模型中生物材料基质定殖的亲合力， 特异性强毒株和非强毒株。表皮 在目标2中， 毒力杆菌胞外多糖的生化特性 有囊化的S.凝胶色谱法测定表皮细胞， 成分分析将允许理解的转换， 正常植物群有机体对病原体有毒性。 目标3： S.当它们准备用于外科手术时， 植入，或者当它们被修改时（例如，射频辉光 排出灭菌材料和抗生素浸渍水泥， 合成血管移植材料）将在体外定量 系统 抗生素对生物膜保护的菌落的有效性 还将评估衬底。 相关表面因素 生物材料如糖蛋白调节膜、表面能 并且将考虑疏水性。 在目标4中，纯化 S.将测试其对表皮细胞的影响。 巨噬细胞的功能，包括吞噬作用和细菌杀伤。 这 将由三名经验丰富的研究人员进行全面的研究 在外科感染生物化学 微生物学和免疫学，并且非常重要，因为它将 阐明负责增加和昂贵的关键因素 生物材料相关感染问题。