OPPA PEPTIDE HOMOLOGUE OF ORAL SPIROCHETES

口腔螺旋体的 OPPA 肽同系物

• 批准号: 6133526
• 负责人: J CHRISTOPHER FENNO
• 金额: $ 3.79万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6133526
• 关键词: Escherichia coli; Treponema; acylation; bacterial proteins; bacterial toxins; endopeptidases; extracellular matrix; gene complementation; gene expression; host organism interaction; membrane proteins; microorganism culture; microorganism immunology; molecular cloning; oral bacteria; pathologic process; periodontium disorder; permease; pore forming protein; posttranslational modifications; recombinant proteins; spirochetes disease

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.

齿垢密螺旋体表面相关蛋白介导牙周病中螺旋体与龈下组织之间的相互作用。具有直接致细胞病变作用的蛋白质一直是研究的主要焦点。然而，很少有人知道的机制，这种肽水解和蛋白水解生物必须利用营养收购，并可能利用特定的信号转导途径或逃避宿主防御。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-宿主相互作用至关重要，并有助于了解由明显致病的螺旋体引起的感染性疾病。本建议探讨了T. Denticola OppA在牙周病发病机制中的作用。该蛋白存在于T.由高度保守的遗传基因座编码，所述基因座包括oppA、-B、-C、-D和-F，它们是ATP结合盒（ABC）转运蛋白家族的组分，所述转运蛋白家族在广泛的细菌中参与肽营养摄取和跨膜环境信号传导。初步研究表明，OppA结合可溶性宿主蛋白丰富的发炎龈下组织。我们假设宿主细胞蛋白质的OppA结合通过以下方式促进生物体的发病机制：（i）宿主肽或蛋白质附着到螺旋体表面，导致宿主反应的调节或逃避;或（ii）肽转运到细胞中用于代谢或环境信号传导途径。该建议补充了本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研究，并包括研究T。牙周病的发病机制。重组表达系统将用于研究OppA的结构和功能，并表征其与龈下环境中存在的宿主细胞外基质和血清组分的相互作用。分子遗传学分析这一假定的运输系统将有助于了解细菌与宿主组织成分在牙周病的相互作用，以及致病性螺旋体的生物学的基本知识。