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:
    8107051
  • 负责人:
  • 金额:
    $ 17.78万
  • 依托单位:
  • 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 2013-03-31
  • 项目状态:
    已结题

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. PUBLIC HEALTH RELEVANCE: Aggregatibacter actinomycetemcomitans is intimately associated with Localized Aggressive Periodontitis in young children, which can result in premature loss of teeth. Coincidentally, A. actinomycetemcomitans is also found in the mouths of Old World primates such as Rhesus (Rh) monkeys. It has been shown that A. actinomycetemcomitans attaches to tissues and kills defense cells in humans and Rh monkeys in a very similar manner. Therefore the Rh monkey provides us with an ideal model in our efforts to unravel some of the mysteries related to the earliest stages of A. actinomycetemcomitans-induced disease. It is also known that A. actinomycetemcomitans produces several factors that are similar to many other bacteria that cause severe infections in man. Therefore, studying A. actinomycetemcomitans in the mouth of Rh monkeys can provide a model that can help us understand how A. actinomycetemcomitans-induced infections develop in a real world environment. This understanding may also have application for other mucosal diseases. We have developed a relationship with the Northeast Primate Research Center and have designed a study that will enable us to place this bacterium in the mouths of Rh monkeys. This study design will allow us to examine how genes direct the way in which A. actinomycetemcomitans attaches to tissues and initiates disease. While attachment is recognized as the first step in infection of skin surfaces that include surfaces like the gums, survival depends on the ability of the bacteria to defend itself against host defense cells. This proposal is designed to examine how certain A. actinomycetemcomitans genes influence early events such as attachment and survival below the gum line. Use of this primate model will allow us to develop ways to interfere with attachment and survival in the hope that we can devise strategies to prevent infections without the need to resort to the use of antibiotics. )
描述(由申请人提供):伴放线菌聚集杆菌(Aa)与年轻成人的局部侵袭性牙周炎(ORG)密切相关。此外,Aa具有多种毒力性状,这些毒力性状与发生在大肠杆菌中的致病事件一致。我们的小组一直在研究与Aa诱导的疾病启动相关的基因,并因此编码负责Aa附着,定植,持久性和龈下存活的毒力性状。到目前为止,我们已经归因于两个Aa自身转运蛋白粘附素基因(aae和apiA)的功能,这与Aa附着到上皮细胞的特异性有关,并表明这些粘附素(以及白细胞毒素)对旧世界(OW)灵长类动物和人类显示出物种特异性。这种特异性使得OW灵长类动物成为研究与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,旨在比较引入OW灵长类动物口腔的两种Aa菌株(一种来自人类,一种来自恒河猴[Rh]猴)的口腔定殖和持久性。在引入猴口腔后的28天内,将在不同时间检查每种菌株的模式、附着水平和定殖。目的1将描述的地形和定量水平的Aa发现在口腔的Rh猴最初,然后比较定植和持久性的两种菌株的Aa(一个人和一只猴子)。在放置之前,猴子将接受刮治和预防加洗必泰治疗。动物将以薄饼形式饲喂Aa,并在饲喂后28天分析定殖和持久性。选择在牙齿上定殖并持续存在的Aa,其水平等于或大于1 x 102 /mL Aa菌落,用于目标2。目的2将评估在BEC、舌和牙齿上发现的Aa的位置、水平和时间,比较未接种和野生型接种的Aa与具有aae和apiA突变的Aa,aae/apiA、flp(纤维状外蛋白)和ltx的双敲除,超过28天。这些实验应该揭示这些基因的重要性,在有关的Aa附件BEC(aae和apiA),牙齿定植(flp)和龈下生存(ltx)在口腔中的OW灵长类动物。建立该模型的效用,使我们不仅可以解剖出附着因子,但也解开其他Aa基因的免疫调节因子,因为它们会影响Aa的发病机制,在未来着眼于预防策略。 公共卫生相关性:伴放线菌聚集菌与幼儿局部侵袭性牙周炎密切相关,可导致牙齿过早脱落。巧合的是,A.伴放线菌也存在于旧大陆灵长类动物如恒河猴(Rh)的口中。结果表明,A.伴放线菌附着在组织上并以非常相似的方式杀死人类和Rh猴的防御细胞。因此,Rh猴为我们提供了一个理想的模型,帮助我们解开与A.伴放线菌引起的病害。已知A.伴随放线菌产生的几种因子与许多其他引起人类严重感染的细菌相似。Rh猴口腔中的放线菌共生体可以提供一个模型,可以帮助我们了解A.伴放线菌引起的感染在真实的世界环境中发展。这种理解也可能适用于其他粘膜疾病。我们已经与东北灵长类动物研究中心建立了关系,并设计了一项研究,使我们能够将这种细菌放入Rh猴的口中。这项研究设计将使我们能够研究基因如何指导A。伴放线菌附着于组织并引发疾病。虽然附着被认为是感染皮肤表面(包括牙龈等表面)的第一步,但存活取决于细菌抵御宿主防御细胞的能力。这个建议的目的是研究如何确定A。伴放线菌基因影响早期事件,如牙龈线以下的附着和存活。使用这种灵长类动物模型将使我们能够开发出干扰依恋和生存的方法,希望我们能够设计出预防感染的策略,而不需要诉诸抗生素的使用。)

项目成果

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DANIEL H FINE其他文献

DANIEL H FINE的其他文献

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{{ truncateString('DANIEL H FINE', 18)}}的其他基金

Oral Colonization of Aggregatibacter in Primates
灵长类动物中聚集杆菌的口腔定植
  • 批准号:
    8709162
  • 财政年份:
    2011
  • 资助金额:
    $ 17.78万
  • 项目类别:
Oral Colonization of Aggregatibacter in Primates
灵长类动物中聚集杆菌的口腔定植
  • 批准号:
    8249833
  • 财政年份:
    2011
  • 资助金额:
    $ 17.78万
  • 项目类别:
ORAL DISTRIBUTION OF AGGREGATIBACTER ACTINOMYCETEMCOMITANS IN OLD WORLD MONKEYS
旧世界猴群中放线菌共生菌的口腔分布
  • 批准号:
    8358013
  • 财政年份:
    2011
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    7932560
  • 财政年份:
    2009
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    7871397
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    7468418
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Early Markers of Aggressive Periodontitis
侵袭性牙周炎的早期标志物
  • 批准号:
    9214235
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    8092569
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    7644510
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:
Localized Aggressive Periodontitis: Microbial & Host Markers for Susceptibility
局部侵袭性牙周炎:微生物
  • 批准号:
    7321527
  • 财政年份:
    2007
  • 资助金额:
    $ 17.78万
  • 项目类别:

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