Characterization of the adhesin-mediated interaction between Staphylococcus epidermidis and implant surfaces to develop an antibody-based therapy for peri-implant inflammation

牙种植体的表面是高度微观和宏观结构化的，以使快速和密集的骨整合到周围的牙槽骨中。不幸的是，这些表面改性还表现出口腔微生物初始粘附和致病性生物膜形成的理想条件，这反过来可能导致植入物周围炎症并导致长期的植入物损失。迄今为止，大多数采用牙周病学治疗种植体周围炎的现有疗法都没有被证明是临床有效的。因此，在种植体周围粘膜炎的早期阶段，开发替代策略来预防或减少种植体表面的微生物定植具有重要的临床意义。此外，种植体周围感染发病机制中的许多基本微生物过程仍然未知。例如，关于微生物表面蛋白质的信息很少，这些蛋白质使细菌能够特异性粘附到植入基质上。因此，拟议研究项目的主要目的是使用表皮葡萄球菌蛋白的蛋白质组学分析来检测和解码这些表面蛋白（粘附素）。S.表皮炎不仅与牙种植体的感染有关，而且还与全身的种植体周围感染有关。为了鉴定S.在负责粘附到植入物表面的表皮上，细菌培养物在常规营养肉汤和粘附在植入物上的营养肉汤中浮游生长。两种蛋白质组将根据不同的蛋白质表达进行分析。为了表征粘附素，将灭活编码蛋白质的相应基因，并通过使用不同的分析方法将修饰菌株与初始细菌菌株在植入物上的粘附潜力进行比较。在小鼠中用重组蛋白获得抗体，以鉴定与种植体周围炎相关的特定微生物并抑制S.种植体上的表皮。该研究项目的总体目标是表征细菌粘附素和植入物基质之间的相互作用，并利用这一知识实施一种新的基于抗体的治疗策略来对抗植入物周围感染。

The surfaces of dental implants are highly micro- and macro-structured to enable quick and intensive osseointegration into the surrounding alveolar bone. Unfortunately, these surface modifications additionally exhibit ideal conditions for the initial adhesion of oral microorganisms and the formation of pathogenic biofilms, which in turn may cause peri-implant inflammation and result in implant loss in the long term. Until now, none of the present therapies against peri-implantitis, which mostly have been adopted from periodontology, has proven to be clinically effective. Therefore, it is of great clinical relevance to develop alternative strategies to prevent or reduce the microbial colonization of the implant surface in the early stages of peri-implant mucositis. Furthermore, many essential microbial processes in the pathogenesis of peri-implant infections are still unknown. For example, information on the surface proteins of microorganisms that enable the specific adhesion of bacteria to implant substrata is rare. Therefore, the primary aim of the proposed research project is to use proteomic analysis of Staphylococcus epidermidis proteins to detected and decode these surface proteins (adhesins). S. epidermidis is not only associated with infections of dental implants, but is also involved with peri-implant infections throughout the body. In order to identify adhesins of S. epidermidis that are responsible for the adhesion to implant surfaces, bacterial cultures are grown planctonic in conventional nutrient broth and in nutrient broth adherent on implants. Both proteomes will be analyzed in terms of differing protein expression. To characterize the adhesins, the corresponding genes encoding the proteins will be inactivated and the modified strains will be compared with the initial bacterial strains regarding their adhesion potential on implants by using different analytical methods. Antibodies are obtained with recombinant proteins in mice in order to identify specific micro-organisms associated with peri-implantitis and to inhibit adhesion of S. epidermidis on implants. The overall aim of the research project is to characterize the interaction between bacterial adhesins and implant substrata and to use this knowledge to implement a newly antibody-based therapeutic strategy against peri-implant infections.