Identification of Uncultivated and Unrecognized Pathogens of Periodontitis

未培养和未被识别的牙周炎病原体的鉴定

基本信息

批准号：
7893783
负责人：
RICARDO P TELES
金额：
$ 70.07万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2011-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In recent years, studies using molecular techniques have indicated that as many as 700 taxa may be detected in the oral cavity, about 300 or more in subgingival plaque, most of which were uncultivable or at least not recognized. It is likely that some of these uncultivable taxa may be periodontal pathogens. Thus, Specific Aim 1 will test the hypothesis that cultivated or uncultivated bacterial species, not yet recognized as pathogens, are associated with periodontitis. In a cross-sectional study, subgingival biofilm samples, taken from the mesial aspect of up to 28 teeth in each of 80 periodontally healthy and 120 periodontitis subjects. Each sample will be split and individually examined using two microbiological assessments. The first method, direct checkerboard hybridization using whole genomic DNA probes to 40 species, will provide positive and negative controls for known species that discriminate periodontitis from health. Extensive experience indicates that species such as P. gingivalis and T. forsythia will differ significantly from health to disease while most remaining species will not. The second microarray chip assay will detect the presence of 300 taxa; i.e. essentially all of the frequently detected cultivable and as yet uncultivated subgingival taxa. The second major criterion to distinguish periodontal pathogens from non pathogens is based on the notion that suppression of a pathogen should lead to clinical improvement, while failure to reduce that species would lead to disease progression. This criterion will be utilized in Specific Aim 2 which will examine the effects of periodontal therapy on newly recognized potential periodontal pathogens and clinical parameters. The 120 periodontitis subjects from Specific Aim 1 will be treated by SRP and 2 weeks of systemically administered metronidazole and amoxicillin. Clinical monitoring and microbiological sampling will be repeated 3 months post therapy and the subgingival plaque samples examined by the two microbiological methods as described in SA1. Associations will be sought between changes in levels of each test taxon and clinical response to therapy. Since periodontal diseases are infections, it would be difficult to suggest studies that are more important than defining the causative agent(s) of the diseases. This study will examine the association of the uncultivated group of species to periodontal health and disease, thus taking the critical first steps in discriminating the pathogenic from commensal organisms. The identification of such pathogens should, over time, lead to better diagnosis of disease, optimal treatment strategies for the individual patient, new therapeutic approaches and carefully targeted approaches to prevention.

描述（由申请人提供）：近年来，使用分子技术的研究表明，在口腔中可以检测到多达700个分类单元，大约300或更多的subgingival斑块，其中大多数是无法培养的或至少不认可的。其中一些不可耕种的分类单元可能是牙周病原体。因此，具体的目标1将检验以下假设：培养或未养殖的细菌物种（尚未公认为病原体）与牙周炎有关。在一项横断面研究中，在80个牙周健康和120名牙周炎受试者中，从多达28颗牙齿的近中牙中取下的副生物膜样品。每个样本将使用两种微生物评估进行分割和单独检查。第一种方法是使用整个基因组DNA探针与40种的直接棋盘杂交杂交，将为已知物种提供阳性和阴性对照，这些物种将牙周炎与健康区分开。丰富的经验表明，牙龈假单胞菌和t。forsythia等物种在健康之间会有很大差异，而大多数剩余物种却不会。第二个微阵列芯片测定法将检测到300个分类单元的存在；即，本质上，所有经常被检测到的可耕种和尚未耕种的亚生物分类单元。将牙周病原体与非病原体区分开的第二个主要标准是基于这样的观念：抑制病原体应导致临床改善，而未能减少该物种会导致疾病进展。该标准将在特定的目标2中使用，该标准将检查牙周治疗对新认识的潜在牙周病原体和临床参数的影响。来自特定目标1的120名牙周炎受试者将通过SRP和2周的全身给药甲硝唑和阿莫西林治疗。治疗后3个月将重复临床监测和微生物采样，以及通过SA1中所述的两种微生物方法检查的尺寸斑块样品。将寻求每个测试分类单元的变化与治疗临床反应之间的关联。由于牙周疾病是感染，因此很难提出比定义疾病的病因更重要的研究。这项研究将研究未经文化的物种与牙周健康和疾病的关联，从而采取了将致病性与共生生物区分开的关键第一步。随着时间的流逝，这种病原体的鉴定应导致更好地诊断疾病，为个体患者的最佳治疗策略，新的治疗方法以及精心靶向的预防方法。