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。 公共卫生相关性:伴生放线杆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,放线菌伴生菌也在东半球灵长类动物如Rheus(Rh)猴子的口腔中发现。已有研究表明,伴生放线菌附着在组织上,以非常相似的方式杀死人类和Rh猴子的防御细胞。因此,Rh猴为我们提供了一个理想的模型,在我们努力解开与伴随放线菌引起的疾病的早期阶段相关的一些谜团。人们还知道,伴生放线杆菌产生的几种因子与许多其他导致人类严重感染的细菌相似。因此,研究放线菌伴生放线菌在Rh猴口腔中的分布可以为我们提供一个模型,帮助我们了解放线菌伴生放线菌感染在真实环境中是如何发展的。这一理解也可能适用于其他粘膜疾病。我们已经与东北灵长类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猴子的口腔中。这项研究设计将使我们能够检查基因如何指导放线菌伴生菌株附着在组织上并引发疾病的方式。虽然附着被认为是感染皮肤表面(包括牙床等表面)的第一步,但生存取决于细菌抵御宿主防御细胞的能力。这项建议旨在研究某些伴生放线放线菌基因如何影响早期事件,如牙周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,希望我们可以设计出预防感染的策略,而不需要诉诸抗生素。)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DANIEL H FINE其他文献

DANIEL H FINE的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.78万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了