Escherichia coli invasion of brain endothelial cells

大肠杆菌侵袭脑内皮细胞

基本信息

批准号：
7160523
负责人：
SHENG-HE HUANG
金额：
$ 24.69万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7160523
关键词：
1-Phosphatidylinositol 3-Kinase Abbreviations Affinity Chromatography Appendix Binding Binding Proteins Biological Assay Blood - brain barrier anatomy Bos taurus Brain Brain Injuries Cattle Caveolae Caveolins Cerebrospinal Fluid Colony-forming units Complex Computer Analysis Cytoskeleton DNA Binding DNA Footprint DNA Microarray Chip DNA Microarray format Disease Dominant-Negative Mutation Endothelial Cells Energy Metabolism Escherichia coli Event Family Fluorescence Geldanamycin Gene Expression Genes Genetic Genistein Glucose Green Fluorescent Proteins Growth Hepatocyte Growth Factor Human In Vitro Island LIM Domain Kinase 1 LIMK1 gene Mediating Membrane Meningitis Methylnitronitrosoguanidine Mutagenesis Neonatal Neuraxis Numbers Oncogene Proteins Oncogenes Operon Organism Oxygen measurement, partial pressure, arterial Pathogenesis Process Promoter Regions Protein Overexpression Protein Tyrosine Kinase Proteins Proto-Oncogene Protein c-met Receptor Protein-Tyrosine Kinases Regulation Research Personnel Rho-associated kinase Role Signal Transduction Signaling Protein Testing Transcription Coactivator Transduction Gene Tyrosine Phosphorylation Virulence Virulence Factors base caveolin 1 cofilin genetic regulatory protein in vivo Model mutant programs protein 50 kDa receptor response yeast two hybrid system

项目摘要

E. coil K1 is the most common gram-negative organism causing neonatal meningitis. One of the least understood issues in the pathogenesis of this disease is how circulating E. coil K1 crosses the blood-brain barrier (BBB) to cause brain injury. We have demonstrated in the in vitro and in vivo models of the BBB that E. coil K1 invasion is a complex process mediated by multiple E. coil invasion determinants, among which the 50-kDa protein encoded by ibeA is unique to E. coil KI. A bovine IbeA-binding protein (IbeABP) has been isolated by IbeA-affinity chromatography from brain microvascular endothelial cells (BMEC). The ibeA locus is a genetic island of meningitic E. coil (GimA) containing 15 genes, which consist of four operons, ptnlPKC, cglDTEC, gcxKRCI and ibeRAT. IbeA is an important virulence factor contributing to E. coil Kl-mediated invasion in BMEC and the 14 other genes may involve in energy metabolism. The regulatory protein IbeR carrying a as4-interaction domain belongs to the NtrC/NifA family of transcriptional activators. It has been shown that anaerobic growth and glucose greatly enhanced E. coil K1 invasion of BMEC. Based on these results, we have hypothesized that the ibeA locus-mediated invasion and energy metabolism are coordinate events in pathogenesis of E. coil K1 meningitis. Interactions between IbeA and its receptor induce cellular responses that are required for E. coil entry of BMECs. Invasion gene expression is regulated by the genetic island GimA including IbeR and environmental signals. Our hypothesis will be tested through the following Specific Aims. (1). To examine how IbeA contributes to E. coil K1 entry of human BMECs. (2). To further characterize the role of IbeABP in E. coil K1 invasion of human BMEC. (3). To determine how E. coil K1 invasion gene expression is regulated by the IbeR and environmental signals (glucose and oxygen tension).

大肠杆菌 K1 是引起新生儿脑膜炎的最常见革兰氏阴性微生物。最少的之一这种疾病发病机制的已知问题是循环大肠杆菌 K1 如何穿过血脑屏障（BBB）导致脑损伤。我们已经在 BBB 的体外和体内模型中进行了演示大肠杆菌K1入侵是一个复杂的过程，由多个大肠杆菌入侵决定因素介导，其中其中 ibeA 编码的 50 kDa 蛋白是大肠杆菌 KI 所独有的。牛 IbeA 结合蛋白 (IbeABP) 已通过 IbeA 亲和层析从脑微血管内皮细胞 (BMEC) 中分离出来。这 ibeA 基因座是脑膜炎大肠杆菌 (GimA) 的遗传岛，包含 15 个基因，其中包括 4 个基因操纵子、ptnlPKC、cglDTEC、gcxKRCI 和 ibeRAT。 IbeA 是大肠杆菌的重要毒力因子。线圈Kl介导的BMEC侵袭和其他14个基因可能参与能量代谢。这携带 as4 相互作用结构域的调节蛋白 IbeR 属于 NtrC/NifA 转录家族激活剂。研究表明，厌氧生长和葡萄糖极大地增强了大肠杆菌 K1 的入侵 BMEC。基于这些结果，我们假设 ibeA 位点介导的侵袭和能量代谢是大肠杆菌 K1 脑膜炎发病机制中的协调事件。 IbeA 和之间的相互作用它的受体诱导大肠杆菌进入 BMEC 所需的细胞反应。侵袭基因表达受包括 IbeR 在内的基因岛 GimA 和环境信号的调节。我们的假设将通过以下具体目标进行检验。 (1).研究 IbeA 如何促进大肠杆菌 K1 进入人类 BMEC。（2）。进一步表征 IbeABP 在大肠杆菌 K1 入侵人 BMEC 中的作用。（3）。确定大肠杆菌 K1 入侵基因表达如何受 IbeR 和环境信号（葡萄糖和氧张力）。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Invasion of Cryptococcus neoformans into human brain microvascular endothelial cells is mediated through the lipid rafts-endocytic pathway via the dual specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3).

新型隐球菌侵入人脑微血管内皮细胞是通过双特异性酪氨酸磷酸化调节激酶 3 (DYRK3) 的脂筏内吞途径介导的。

DOI：
发表时间：
2011-10-07
期刊：
影响因子：
0
作者：
Huang, Sheng;Long, Min;Wu, Chun;Kwon;Chang, Yun C;Chi, Feng;Lee, Susan;Jong, Ambrose
通讯作者：
Jong, Ambrose

Involvement of human CD44 during Cryptococcus neoformans infection of brain microvascular endothelial cells.

新型隐球菌感染脑微血管内皮细胞期间人 CD44 的参与。

DOI：
发表时间：
2008-06
期刊：
影响因子：
3.4
作者：
Jong, Ambrose;Wu, Chun;Shackleford, Gregory M;Kwon;Chang, Yun C;Chen, Han;Ouyang, Yannan;Huang, Sheng
通讯作者：
Huang, Sheng

Identification of IbeR as a stationary-phase regulator in meningitic Escherichia coli K1 that carries a loss-of-function mutation in rpoS.

鉴定 IbeR 作为脑膜炎大肠杆菌 K1 的稳定相调节剂，该大肠杆菌 K1 携带 rpoS 功能丧失突变。