EPIDEMIOLOGY OF A ACTINOMYCETEMCOMITANS IN ORAL DISEASE

这是一个香农奖提供部分支持的研究 项目不属于指定的研究所的资金范围，但 都处于优秀的边缘。 香农奖旨在 提供支持，以测试该方法的可行性;进一步发展 测试和完善研究技术;进行二次分析 可用的数据集;或进行离散项目， PI的研究能力或为已经存在的 有价值的申请。 下面的摘要摘自原文 主要研究者提交的文件。 兼性革兰氏阴性细菌放线杆菌 放线菌属（actinomycetemcomitans），已被认为是一种重要的病原菌， 牙周病的危害有哪些？ 这种细菌在 局限性青少年牙周炎（LJP）一直是激烈的主题， 调查 最近，分子方法，如DNA 指纹和限制性片段长度多态性（RFLP） 分析已被用于了解传播和流行病学 在LJP的细菌。 在这个提议中，假设一个子集 人源A.伴随放线菌， 将检测LJP的克隆。 遗传变异的研究， 确定的A.伴放线菌 有助于鉴定细菌的特定克隆类型 有可能是致命的或相对无毒的。 的 本项目的具体目标是：（1）确定遗传变异 A.自然种群放线菌共生菌。 多位点 酶电泳和任意引物聚合酶链反应 将用于确定细菌物种的克隆性， 来自LJP家族的临床分离株的良好表征集合。 将通过这些方法鉴定的克隆系与基因型 以前以RFLP为特征的群体。 目标是建立 某些克隆类型的A.伴随放线菌与 LJP发作。 (2)为了描述组织中的差异， 这些克隆类型的A. 伴放线菌与牙周健康的关系 status. RFLP分析将用于确定遗传异质性 白细胞毒素操纵子中与特异性 在疾病和健康的情况下克隆类型。 如果是这样， 基因表达的差异可能与致病潜力有关 个体克隆。 (3)评估结构中的克隆变异性 的特定细胞表面成分。伴放线菌 的 目的是确定这些克隆类型的A. 与牙周疾病相关的放线菌共生菌 表达脂多糖（LPS）独特分子种类状态， 主要的外膜蛋白。 将特别强调 检测主要外膜蛋白的结构差异 其功能相当于免疫球蛋白Fc受体。 克隆差异 这些细胞表面成分，如在白细胞毒素的情况下， 支持的概念，有毒和无毒的变种或菌株， A.伴放线菌存在于人类口腔植物群中。 因此 本研究中获得的信息将导致识别 细菌“菌株”和产品，应该作为最 适合研究的主题，重点是流行病学，诊断学， 致病性和宿主免疫反应的研究。

This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. The facultative gram-negative bacterium, Actinobacillus actinomycetemcomitans, has been recognized as an important pathogen in various forms of periodontal disease. The role of this bacterium in localized juvenile periodontitis (LJP) has been the subject of intense investigation. More recently, molecular approaches such as DNA fingerprinting and restriction fragment length polymorphism (RFLP) analysis have been used to learn about the transmission and epidemiology of this bacterium in LJP. In this proposal, the hypothesis that a subset of human isolates of A. actinomycetemcomitans that are associated with LJP are clonal will be tested. The study of the genetic variability and clonality of defined populations of A. actinomycetemcomitans will facilitate the identification of specific clonal types of the bacterium that have the potential to be virulent or relatively avirulent. The specific aims of the project are: (1) To determine the genetic variation of natural populations of A. actinomycetemcomitans in LJP. Multilocus enzyme electrophoresis and arbitrarily primed polymerase chain reaction will be used to determine the clonality of the bacterial species in a well-characterized collection of clinical isolates from LJP families. Clonal lines identified by these methods will be compared to genotypic groups previously characterized by RFLP. The objective is to establish that certain clonal types of A. actinomycetemcomitans correlate with the onset of LJP. (2) To characterize differences in the organization of putative virulence genes among members of those clonal types of A. actinomycetemcomitans associated with a disease and healthy periodontal status. RFLP analysis will be used to determine if genetic heterogeneity in a leukotoxin operon correlates with the distribution of specific clonal types in cases of disease and health. If this is the case, differences in gene expression can be related to the pathogenic potential of individual clones. (3) To assess clonal variability in the structure of specific cell surface components of A. actinomycetemcomitans. The objective is to determine if those clonal types of A. actinomycetemcomitans that are associated with a diseased periodontal status express unique molecular species of lipopolysaccharide (LPS) and the major outer membrane proteins. Particular emphasis will be placed on detecting structural differences in the major outer membrane protein that functions as an immunoglobulin Fc receptor. Clonal differences in these cell surface components, as in the case of the leukotoxin, would support the concept that virulent and avirulent variants or strains of A. actinomycetemcomitans exist in the human oral flora. Thus, the information obtained in this study will lead to the identification of bacterial "strains" and products that should serve as the most appropriate subjects for studies that focus on epidemiology, diagnostics, pathogenicity and host immune response in periodontal disease research.