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，并制定预防或控制螺旋体感染的方法。有大量证据表明螺旋体，特别是齿形T，是牙周病的病原。在急性坏死性溃疡性牙龈炎（ANUG）和某些形式的牙周病中，螺旋体可能占细菌菌群的50%以上。在此之前，我们已经帮助将已知的已培养密螺旋体的数量从4种增加到10种，并确定了另外47种目前无法培养的密螺旋体。我们已经开发了基于16S rRNA的DNA探针，可以在临床样品中识别可培养和不可培养的密螺旋体。本提案的目的1将确定哪些螺旋体与各种口腔传染病有关，以及除齿状螺旋体外的密螺旋体如何与Socransky先前描述的牙周细菌复合物相关。确定相关病原体是任何传染病研究中必不可少的第一步。目的2将获得一个主要表面抗原msp的分子认识。我们将确定个体中msp基因型的多样性，以及msp基因型在细菌种群中如何随时间变化。预防措施，如疫苗，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。本提案的目标3将获得关于基因组大小和宿主关联程度的信息，这些信息反映了每种已知可培养的口服密螺旋体的基因组大小减少。最后的目的将检查麦芽链球菌的基因组库，第二口腔密螺旋体涉及口腔感染。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心绞痛）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.