CULTIVABLE & UNCULTIVABLE PERIODONTAL SPIROCHETES

拟议研究的长期目标是确定螺旋体在口腔传染病病因学中的作用，并开发预防或控制螺旋体感染的方法。有大量的证据表明，螺旋体，特别是齿垢锥虫，作为牙周病的病原体。 在急性坏死性溃疡性牙龈炎（ANUG）和某些形式的牙周病中，螺旋体可占细菌植物群的50%以上。 在此之前的补助金，我们已经帮助扩大了已知的培养密螺旋体的数量从4到10种，并确定了额外的47个目前无法培养密螺旋体物种。 我们已经开发了基于16S rRNA的DNA探针，其允许鉴定临床样品中可培养和不可培养的密螺旋体。 本建议的目的1将确定哪些螺旋体与各种口腔感染性疾病有关，以及除了T。与Socransky先前描述的牙周细菌复合体有关。 确定相关的病原体是任何传染病研究中必不可少的第一步。 目的二是从分子水平上了解T.齿垢 我们将确定个体中msp基因型的多样性以及细菌种群中msp基因型如何随时间推移而变化。 疫苗等预防措施需要了解主要抗原表位的多样性以及抗原多样性的表达如何随时间变化。 本提案的目的3将获得关于基因组大小和宿主关联程度的信息，如通过每种已知可培养的口腔密螺旋体的基因组大小减小所反映的。 最后的目的将检查T的基因组库。嗜麦芽窄食单胞菌，第二口腔密螺旋体牵连在口腔感染。 这项基因组调查将提供对生物体代谢和致病能力的深入了解，并将确定疫苗或药物治疗的靶点。 这项研究将提高我们对口腔细菌的主要部分的理解，并将为最终控制和预防口腔传染病，如牙周炎，冠周炎，ANUG，坏疽性口炎和路德维希咽峡炎提供必要的信息。

The long-term goal of the proposed research is to determine the role of spirochetes in the etiology of oral infectious diseases and to develop means to prevent or control spirochete infections. There is substantial evidence implicating spirochetes, particularly T denticola, as etiologic agents in periodontal diseases. In acute necrotizing ulcerative gingivitis (ANUG) and some forms of periodontal disease, spirochetes may comprise over 50 percent of the bacterial flora. Previously in this grant, we have helped to expand the number of known cultivated treponemes from 4 to 10 species, and identified an additional 47 currently uncultivable Treponema species. We have developed 16S rRNA based DNA probes that allow identification of cultivable and uncultivable treponemes in clinical samples. Aim 1 of this proposal will determine which spirochetes are associated with a variety of oral infectious diseases, and how treponemes other than T. denticola relate to Socransky's previously described periodontal bacterial complexes. Determining associated pathogens is a requisite first step in any study of infectious disease. Aim 2 will obtain a molecular understanding of msp, a major surface antigen of T. denticola. We will determine the diversity of msp genotypes in individuals and how msp genotypes shift over time in bacterial populations. Preventive measures, such as vaccines, require an understanding of the diversity of epitopes of the major antigens and how expression of antigen diversity varies over time. Aim 3 of this proposal will obtain information on the genome size and degree of host association as reflected by genome size reduction for each of the known cultivable oral treponemes. The final Aim will examine the genomic repertoire of T. maltophilum, a second oral treponeme implicated in oral infections. This genome survey will provide insight into the metabolic and pathogenic capabilities of the organism and will identify targets for vaccines or drug treatment. This research will improve our understanding of a major segment of the oral bacteria and will provide information necessary for the eventual control and prevention of oral infectious diseases such as periodontitis, pericoronitis, ANUG, noma, and Ludwig's angina.