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Oral Colonization of Aggregatibacter in Primates

灵长类动物中聚集杆菌的口腔定植

基本信息

批准号：
8709162
负责人：
DANIEL H FINE
金额：
$ 15.3万
依托单位：
RBHS-SCHOOL OF DENTAL MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8709162
关键词：
Oral Colonization Aggregatibacter Primates

项目摘要

DESCRIPTION (provided by applicant): Aggregatibacter actinomycetemcomitans (Aa) is intimately associated with Localized Aggressive Periodontitis (LAP) in young adults. Further, Aa possesses a variety of virulence traits that are consistent with pathogenic events that occur in LAP. Our group has been studying genes that are related to Aa-induced disease initiation and as such encode virulence traits responsible for Aa attachment, colonization, persistence, and subgingival survival. Thus far we have ascribed functions for two Aa autotransporter adhesin genes (aae and apiA) that are related to the specificity of Aa attachment to epithelium and have shown that these adhesins (as well as Leukotoxin) show species specificity for Old World (OW) primates and humans. This specificity makes the OW primate an ideal model for studying early events related to Aa infection with an eye toward development of preventive strategies. This R21 application consists of two Aims and is designed to compare oral colonization and persistence of two Aa strains (one from humans and one from Rhesus [Rh] monkeys) that are introduced into the oral cavity of OW primates. Each strain will be examined for its pattern, level of attachment, and colonization at different times over a 28-day period following introduction into the mouth of the monkey. Aim 1 will describe the topographical and quantitative level of Aa found in the mouths of Rh monkeys initially and then compare colonization and persistence of the two strains of Aa (one human and one monkey). Before placement, monkeys will receive scaling and prophylaxis plus chlorhexidine treatment. Animals will be fed Aa in a pancake and colonization and persistence will be analyzed 28 days after feeding. The Aa that colonizes and persists on teeth at a level equal to or greater than 1 x 102 /mL colonies of Aa will be selected for use in Aim 2. Aim 2 will assess the location, level and timing of Aa found on BECs, tongue and teeth comparing un-inoculated and wild type inoculated Aa to Aa with mutations in aae and apiA, a double knockout of aae/apiA, flp (the fibrillar outer protein) and ltx over a 28-day period. These experiments should reveal the importance of these genes in relation to Aa attachment to BECs (aae and apiA), to tooth colonization (flp) and to subgingival survival (ltx) in the oral cavity of OW primates. Establishing the utility of this model should allow us not only to dissect out attachment factors but also to unravel immune modulation factors from other Aa genes as they affect Aa pathogenesis in the future with an eye toward preventive strategies.

描述(由申请人提供)：伴生放线杆菌(AA)与年轻人的局限性侵袭性牙周炎(LAP)密切相关。此外，AA具有多种毒力特征，这些特征与LAP中发生的致病事件一致。我们小组一直在研究与AA诱导的疾病启动相关的基因，并因此编码与AA附着、定植、持久性和牙龈下存活有关的毒力特征。到目前为止，我们已经确定了两个AA自身转运蛋白粘附素基因(aae和apia)的功能，它们与AA附着上皮的特异性有关，并表明这些粘附素(以及白质毒素)对东半球(OW)灵长类动物和人类具有物种特异性。这种特异性使OW灵长类成为研究与AA感染相关的早期事件的理想模型，并着眼于预防策略的发展。该R21应用程序由两个目标组成，旨在比较两种AA菌株(一种来自人类，一种来自恒河猴)被引入OW灵长类动物口腔中的口腔定植和持久性。每个菌株都将在进入猴子口腔后的28天内，在不同的时间被检查其模式、依附程度和定植情况。目的1将首先描述在Rh猴口腔中发现的AA的地形和数量水平，然后比较两种AA株(一种人和一种猴子)的定植和持久性。在放置之前，猴子将接受洗必泰和洗必泰治疗。动物将被喂以煎饼形式的AA，并将在喂食28天后分析定殖率和持久性。目标2将评估在BEC、舌头和牙齿上发现的AA的位置、水平和时间，比较未接种和野生型AA与AAE和ApIA的突变、AAE/Apia、FLP(纤维外膜蛋白)和LTX在28天内的突变。这些实验应该揭示这些基因与AA附着于BECs(AAE和APIA)、牙齿定植(FLP)和OW灵长类口腔中的牙龈下生存(LTX)有关的重要性。建立这个模型的实用性应该使我们不仅可以剖析出依附因子，而且还可以从其他AA基因中解开免疫调节因子，因为它们影响着未来的AA发病机制，并着眼于预防策略。