Host factors and bacterial meningitis

宿主因素与细菌性脑膜炎

基本信息

  • 批准号:
    9270628
  • 负责人:
  • 金额:
    $ 35.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-30 至 2020-05-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Bacterial meningitis continues to be an important cause of mortality and morbidity, such as developmental delay, hearing loss and cognitive impairment. The Metropolitan Atlanta Developmental Disabilities Surveillance Program identified bacterial meningitis as the leading postnatal cause of developmental disabilities. A major contributing factor to such mortality and morbidity is our incomplete knowledge on the pathogenesis of this disease. E. coli is the most common Gram-negative bacillary organism causing meningitis. Several lines of evidence from human cases and experimental animal models of E. coli meningitis indicate that E. coli penetration into the brain follows a high level f bacteremia and cerebral capillaries are the portal of E. coli entry into the brain. Since E. coli entry into the brain occurred in the cerebral microvessels, we developed the blood-brain barrier model with human brain microvascular endothelial cells (HBMEC) to study E. coli penetration of the blood-brain barrier. Our HBMEC monolayer, upon cultivation on collagen-coated Transwells, exhibits spatial organization of tight and adherens junction proteins as well as a polarized monolayer, a unique property of the blood-brain barrier endothelial cells. We have shown for the first time that meningitis-causing E. coli strains exhibit the ability to invade the HBMEC monolayer and that the ability of HBMEC invasion is correlated with E. coli penetration into the brain in vivo. The underlying mechanisms involved in E. coli penetration of the blood-brain barrier, however, remain incompletely understood. These findings indicate that new approaches are needed to investigate E. coli penetration of the blood-brain barrier. We have used E. coli invasion of HBMEC monolayer as a biologically relevant new approach for discovery of targets affecting E. coli penetration of the blood-brain barrier. This application is to take advantage of the new targets identified from our chemical screen for investigating how they contribute to E. coli penetration of the blood-brain barrier in vitro and in vivo. Characterization of such targets will demonstrate a novel strategy exploited by meningitis-causing E. coli strains for penetration of the blood-brain barrier, the essential step in the development of E. coli meningitis.
 描述(由申请方提供):细菌性脑膜炎仍然是死亡和发病的重要原因,如发育迟缓、听力损失和认知障碍。大都会亚特兰大发育障碍监测计划确定细菌性脑膜炎是发育障碍的主要产后原因。造成这种死亡率和发病率的一个主要因素是我们对这种疾病的发病机制认识不全。E.大肠杆菌是引起脑膜炎的最常见的革兰氏阴性杆菌。从人类病例和实验动物模型中获得的几条证据。大肠杆菌脑膜炎表明,E.大肠杆菌进入脑组织后,脑毛细血管是大肠杆菌的入口。大肠杆菌进入大脑自E.大肠杆菌进入脑的途径是脑微血管,我们建立了人脑微血管内皮细胞(HBMEC)血脑屏障模型,研究了大肠杆菌的血脑屏障功能。大肠杆菌穿透血脑屏障。我们的HBMEC单层,在胶原包被的Transwell上培养后,表现出紧密和粘附连接蛋白的空间组织以及极化单层,这是血脑屏障内皮细胞的独特性质。我们首次证明了脑膜炎致病菌E。大肠杆菌具有侵袭HBMEC单层的能力,HBMEC的侵袭能力与大肠杆菌的侵袭能力有关。大肠杆菌在体内渗透到大脑中。E.然而,大肠杆菌对血脑屏障的穿透仍然不完全清楚。这些发现表明,需要新的方法来研究E。大肠杆菌穿透血脑屏障。我们使用E。大肠杆菌侵袭HBMEC单层作为一种生物学相关的新方法,发现影响大肠杆菌的目标。大肠杆菌穿透血脑屏障。本申请是利用我们的化学筛选确定的新靶标来研究它们如何对E.在体外和体内的血脑屏障的大肠杆菌渗透。对这些靶点的表征将证明脑膜炎致病性大肠杆菌利用的一种新策略。大肠杆菌菌株穿透血脑屏障,这是大肠杆菌发展的关键步骤。大肠杆菌脑膜炎。

项目成果

期刊论文数量(0)
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Kwang S Kim其他文献

Invasion of Intestinal Epithelial Cells In Vitro by Escherichia coli Is Influenced by Microaerophilic Conditions and the Presence of ibe Genes † 890
大肠杆菌在体外对肠上皮细胞的侵袭受微需氧条件和 ibe 基因存在的影响†890
  • DOI:
    10.1203/00006450-199804001-00911
  • 发表时间:
    1998-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Michelle M Pietzak;Julie L Badger;Carol A Wass;Dan W Thomas;Kwang S Kim
  • 通讯作者:
    Kwang S Kim

Kwang S Kim的其他文献

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{{ truncateString('Kwang S Kim', 18)}}的其他基金

Cryptococcal Exploitation of the Blood-Brain Barrier
隐球菌对血脑屏障的利用
  • 批准号:
    10012330
  • 财政年份:
    2020
  • 资助金额:
    $ 35.44万
  • 项目类别:
E. coli penetration of the blood-brain barrier
大肠杆菌穿透血脑屏障
  • 批准号:
    9243956
  • 财政年份:
    2016
  • 资助金额:
    $ 35.44万
  • 项目类别:
Pathogenesis of bacterial meningitis
细菌性脑膜炎的发病机制
  • 批准号:
    9303283
  • 财政年份:
    2016
  • 资助金额:
    $ 35.44万
  • 项目类别:
Discovery of Novel Therapeutics for Fungal Pathogens
真菌病原体新疗法的发现
  • 批准号:
    9393966
  • 财政年份:
    2016
  • 资助金额:
    $ 35.44万
  • 项目类别:
Pathogenesis of bacterial meningitis
细菌性脑膜炎的发病机制
  • 批准号:
    9167645
  • 财政年份:
    2016
  • 资助金额:
    $ 35.44万
  • 项目类别:
E. coli penetration of the blood-brain barrier
大肠杆菌穿透血脑屏障
  • 批准号:
    9034789
  • 财政年份:
    2016
  • 资助金额:
    $ 35.44万
  • 项目类别:
Host factors and bacterial meningitis
宿主因素与细菌性脑膜炎
  • 批准号:
    9028219
  • 财政年份:
    2015
  • 资助金额:
    $ 35.44万
  • 项目类别:
Leukotrienes and blood-brain barrier
白三烯和血脑屏障
  • 批准号:
    8640878
  • 财政年份:
    2010
  • 资助金额:
    $ 35.44万
  • 项目类别:
Leukotrienes and blood-brain barrier
白三烯和血脑屏障
  • 批准号:
    8071224
  • 财政年份:
    2010
  • 资助金额:
    $ 35.44万
  • 项目类别:
Leukotrienes and blood-brain barrier
白三烯和血脑屏障
  • 批准号:
    8451256
  • 财政年份:
    2010
  • 资助金额:
    $ 35.44万
  • 项目类别:

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