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

牙种植体的表面具有高度的微观和宏观结构，能够快速和密集地与周围的牙槽骨结合。不幸的是，这些表面修饰还为口腔微生物的初始黏附和致病生物膜的形成提供了理想的条件，这反过来可能导致种植体周围的炎症，并导致种植体的长期丢失。到目前为止，目前针对种植体周炎的治疗方法大多来自牙周学，没有一种方法被证明是临床有效的。因此，在种植体周围黏膜炎的早期阶段，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，在种植体周围感染的发病机制中，许多重要的微生物过程仍然未知。例如，有关微生物表面蛋白质的信息很少，这些蛋白质使细菌与植入底物具有特定的粘附性。因此，建议的研究项目的主要目的是利用表皮葡萄球菌蛋白的蛋白质组分析来检测和解码这些表面蛋白(粘附素)。表皮葡萄球菌不仅与牙科种植体的感染有关，而且还与种植体周围的全身感染有关。为了确定与种植体表面粘连有关的表皮葡萄球菌粘附素，在常规营养肉汤和附着在种植体上的营养肉汤中进行细菌培养。这两个蛋白质组将根据不同的蛋白质表达进行分析。为了确定粘附素的特征，相应的编码蛋白质的基因将被失活，并将使用不同的分析方法将修改后的菌株与原始细菌菌株进行比较，以了解它们在植入物上的黏附能力。在小鼠体内用重组蛋白获得抗体，以识别与种植体周围炎相关的特定微生物，并抑制表皮葡萄球菌在植入物上的黏附。该研究项目的总体目标是表征细菌粘附素和种植底物之间的相互作用，并利用这一知识来实施一种新的基于抗体的治疗策略，以防止种植体周围感染。

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.