OPPA PEPTIDE HOMOLOGUE OF ORAL SPIROCHETES

齿垢密螺旋体的表面相关蛋白介导牙周疾病中螺旋体和龈下组织之间的相互作用。具有直接细胞病变作用的蛋白质一直是研究的主要焦点。然而，人们对这种肽分解和蛋白水解生物必须利用的营养获取机制以及可能用于特定信号传导途径或逃避宿主防御的机制知之甚少。这些过程可能是许多传染病发展的关键因素。口腔螺旋体的分子遗传学研究对于分析牙周病中螺旋体与宿主的相互作用至关重要，并有助于了解由明显致病的螺旋体引起的传染病。本提案探讨了 T. denticola OppA 在牙周发病机制中的潜在作用。这种蛋白质存在于 T. denticola 的表面提取物中，由高度保守的基因位点编码，其中包括 oppA、-B、-C、-D 和 -F，它们是 ATP 结合盒 (ABC) 转运蛋白家族的组成部分，参与多种细菌的肽营养吸收和跨膜环境信号传导。初步研究表明，OppA 与发炎龈下组织中丰富的可溶性宿主蛋白结合。我们假设 OppA 与宿主细胞蛋白的结合通过以下方式促进生物体的发病机制：(i) 将宿主肽或蛋白质积聚到螺旋体表面，从而调节或逃避宿主反应； (ii) 肽转运至细胞内用于代谢或环境信号传导途径。该提案补充了该实验室正在进行的由外膜孔蛋白和蛋白酶组成的膜复合物组装的研究，并包括研究牙周炎中 T. denticola 的作用的新方法。重组表达系统将用于研究 OppA 的结构和功能，并表征其与宿主细胞外基质和龈下环境中存在的血清成分的相互作用。这种假定的转运系统的分子遗传学分析将有助于了解牙周病中细菌与宿主组织成分的相互作用，以及致病性螺旋体生物学的基础知识。

Surface-associated proteins of Treponema denticola mediate interactions between the spirochete and sub-gingival tissues in periodontal diseases. Proteins having direct cytopathic effects have been a primary focus of research. However, very little is known of the mechanisms this peptidolytic and proteolytic organism must utilize for nutrient acquisition, and may utilize in specific signaling pathways or in evasion of host defenses. These processes can be key factors in the development of many infectious diseases. Molecular genetic studies of oral spirochetes are crucial to analysis of spirochete-host interactions in periodontal diseases and contribute to understanding infectious diseases caused by frankly pathogenic spirochetes. The present proposal explores the potential role of T. denticola OppA in periodontal pathogenesis. This protein, present in surface extracts of T. denticola, is encoded by a highly conserved genetic locus that includes oppA, -B, -C, -D and -F, the components of an ATP-binding cassette (ABC) transporter family involved in pep-tide nutrient uptake and trans- membrane environmental signaling in a wide range of bacteria. Preliminary studies showed that OppA bound soluble host proteins abundant in inflamed subgingival tissue. We hypothesize that OppA binding of host cell proteins contributes to the pathogenesis of organism by (i) accretion of host peptides or proteins to the spirochete surface, resulting in modulation or evasion of host responses; or (ii) peptide transport into the cell for use in metabolic or environmental signaling pathways. This proposal complements studies underway in this laboratory on assembly of membrane complexes comprised of outer membrane porins and proteases, and includes novel approaches to the study of the role of T. denticola in periodontal pathogenesis. Recombinant expression systems will be used to investigate the structure and function of OppA and to characterize its interaction with host extracellular matrix and serum components present in the subgingival environment. Molecular genetic analysis of this putative transport system will contribute to the understanding of bacterial interactions with host tissue components in periodontal diseases, as well as to basic knowledge of the biology of pathogenic spirochetes.