Distribution correlation of P. gingivalis and S. cristatus in dental plaque

描述(申请人提供)：成人牙周炎在不同种族之间分布不均，非西班牙裔黑人的发病率明显高于非西班牙裔白人，即使考虑到糖尿病等协变量和其他健康和社会因素。据报道，与未患牙周炎的受试者相比，有齿状齿的受试者口腔病原体P.gigivalis的滴度更高，正如预期的那样。我们的实验室首次报道了一例肺炎链球菌和牙龈假单胞菌之间的跨属传播。我们鉴定了一种新的信号蛋白--精氨酸脱亚胺酶(Arca) 牙龈假单胞菌通过抑制FIMA基因的表达来做出反应的分子，FIMA基因编码长菌毛的主要亚单位蛋白。后者是牙龈假单胞菌的细菌定植和宿主细胞入侵所必需的。因此，这一项目将检验这样的假设：a)冠状沙门氏菌是一种有益的细菌，在预防牙龈假单胞菌在口腔中的定植方面发挥着重要作用；以及b)发病率的增加 非裔美国人的牙周炎可能是由于与白人相比，这些受试者中口腔金黄色葡萄球菌与牙龈假单胞菌的比率降低，或者是黑人和白人的FIMA基因类型不同。因此，我们的目标是：1)确定中度牙周炎、重度牙周炎和牙周健康人牙菌斑中的葡萄球菌和牙龈假单胞菌的分布，并比较每组中非裔美国人和高加索人的微生物谱(特别是葡萄球菌和牙龈假单胞菌)；以及2)检查这些葡萄球菌和牙龈假单胞菌的患病率与不同FIMA基因的相关性。为了实现这些目标，我们将招募三组受试者：那些牙周健康的人，或者患有中度和重度牙周炎的人。每个小组将由成年的非裔美国人和高加索人组成，男性和女性。排除标准将包括糖尿病、艾滋病毒/艾滋病和其他健康标准，如怀孕。所有受试者都将接受牙周状况和病史的全面口腔检查。将收集牙菌斑的微生物样本。犯罪链球菌和牙龈假单胞菌的流行率将通过qPCR分析来确定，不同FIMA基因型的流行率也将通过qPCR分析来确定。我们预计，拟议的研究将提供关于牙周炎发病机制的重要信息，以及在这两个人群中发现的微生物生物膜，并将为未来的扩展研究铺平道路，从长远来看，重点是开发旨在消除牙龈假单胞菌定植的适当干预策略。 公共卫生相关性：牙龈卟啉单胞菌是一种与成人牙周炎有关的主要病原体，影响到很大一部分人口，在美国成年人中，非裔美国人比白人更有可能患牙周炎，优势比在2.09到2.4之间。这项建议的目的是调查非洲裔美国人和高加索人中中度牙周炎、重度牙周炎和牙周健康个体的微生物谱。这项工作的结果将大大加强我们对土著微生物群落在影响人类健康和健康差距方面的关键作用的理解。

DESCRIPTION (provided by applicant): Adult periodontitis is disproportionally distributed among races, and has a significantly higher incidence in non- Hispanic blacks compared to non-Hispanic whites, even when co-variates such as diabetes and other health and social factors have been taken into account. Titers to the oral pathogen P. gingivalis are reported to be higher, as anticipated, in dentate subjects with, compared to those without periodontitis. Our laboratory was to first to report an intergeneric communication between Streptococcus cristatus and P. gingivalis. We identified a surface protein of S. cristatus, arginine deiminase (ArcA), as a signal molecule to which P. gingivalis responds by repressing the expression of the fimA gene, which codes for the major subunit protein of long fimbriae. The latter is required for bacterial colonization of P. gingivalis and host cell invasion. Therefore this project will test the hypothess that: a) S. cristatus serves as a beneficial bacterium and plays an important role in the prevention of P. gingivalis colonization of the oral cavity; and b) that the increased incidence of periodontitis in African-Americans may be due to either a decreased ratio of oral S. cristatus: P. gingivalis in these subjects compared to whites, or that the FimA genotypes may differ in blacks vs. whites. Our aims therefore are to: 1) determine the distribution of S. cristatus and P. gingivalis in dental plaques of those with moderate periodontitis, severe periodontitis and periodontal healthy individuals, and compare microbial profiles (especially S. cristatus and P. gingivalis), in Africa Americans versus Caucasians within each group; and 2) to examine the correlation of these prevalence of S. cristatus and P. gingivalis with different FimA genotypes. To achieve these aims, we will recruit three groups of subjects: those with a healthy periodontium, or with moderate versus severe periodontitis. Each group will be composed of adult African American and Caucasian males and females. Exclusion criteria will include diabetes, HIV-AIDs and other health criteria such as pregnancy. All subjects will receive a full-mouth examination of periodontal status and a medical history. Microbial samples from dental plaque will be collected. The prevalence of S. cristatus and P. gingivalis will be determined by qPCR analysis, as will the prevalence of different FimA genotypes. We anticipate that the proposed studies will provide important information regarding the pathogenesis of periodontitis, and the microbial biofilms found in these two populations and will pave the way for extended studies in future, focused in the longer term on the development of appropriate interventional strategies targeting at eliminating of P. gingivalis colonization. PUBLIC HEALTH RELEVANCE: Porphyromonas gingivalis is a primary pathogen associated with adult periodontitis affecting a large proportion of the population, and African Americans are more likely to exhibit periodontitis than whites with odds ratio between 2.09 and 2.4 in US adults. The goal of this proposal is to investigate microbial profiles of moderate periodontitis, severe periodontitis and periodontal health individuals in African Americans and Caucasians. Findings from this work will significantly enhance our understanding of the key role of indigenous microbial communities in influencing human health and health disparities.