NEUROENDOCRINE MEDIATION OF E. COLI 0157:H7 INFECTION

大肠杆菌 0157:H7 感染的神经内分泌调节

• 批准号: 6511043
• 负责人: MARK LYTE
• 金额: $ 26.68万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511043
• 关键词: Escherichia coli 0157:H7; bacteria infection mechanism; gastrointestinal infection; laboratory mouse; microorganism growth; neuroendocrine system; norepinephrine; physiologic stressor; virulence

This application proposes the new theory of directed neuroendocrine- bacterial interactions as a mechanism governing the ability of an enteric pathogen to infect a host. This hypothesis is based on the in vitro and in vivo ability of the neuro-endocrine hormone norepinephrine (NE) to increase growth and production of virulence-associated factors of the enteric pathogen Escherichia coli O157:H7. High concentration of NE occur in foods such as ground beef which are contaminated by E. coli O157:H7. Equally high concentrations of NE also occur within the gastrointestinal tract due to enteric nervous system activity. The proposed research will therefore examine whether the presence of NE from the time of E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157:H7 contamination of NE-rich foods to infection within the gut may be a factor mediating the development of hemorrhagic colitis. Results from this laboratory have shown that the effect of NE on E. coli O157: H7 is due to the production of an autoinducer of growth. Thus, our Specific Aims are: 1) To determine the ability of a purified diet supplemented with levels of NE found in commonly contaminated foods to "prime" E. coli O157:H7 for the NE-rich environment within the gastrointestinal system; 2) To examine the ability of E. coli O157:H7 isolated from gastrointestinal trat of stressed and non-stressed mice since differences in luminal levels of NE between stressed and control animals would provide greater understanding of the recognized ability of stress to alter susceptibility to colitis; 4) To determine the ability of stress of alter the susceptibility of mice to oral challenge with E. coli O157:H7 exposed in vitro to control of NE supplemented diets; 5) To examine whether blockage of NE release within the gastrointestinal tract can alter susceptibility to challenge with E. coli P157:H7; and 6) To purify the serum-bound form of the NE-induced E. coli O157:H7 autoinducer of growth and determine its structure which may provide the basis for the development of agents to specifically interrupt bacterial division as well as identify the gene(s) involved in its production. Collectively, the above aims will seek to establish a direct cause and effect relationship between the NE content within food and the gastrointestinal trat to influence the ability of E. coli O157:H7 to cause infection. The demonstration of direct neuroendocrine-bacterial interaction as a mechanism in the pathogenesis of E. coli O157:H7 infection may yield new treatments for both the prevention and treatment of hemorrhagic colitis.

本申请提出了定向神经内分泌-细菌相互作用作为控制肠道病原体感染宿主能力的机制的新理论。这一假设是基于神经内分泌激素去甲肾上腺素（NE）在体外和体内增加肠道病原体大肠杆菌O 157：H7的生长和毒性相关因子产生的能力。在被大肠杆菌污染的牛肉等食品中，NE含量较高。coli O157：H7。由于肠神经系统活动，胃肠道内也会出现同样高浓度的NE。因此，拟议的研究将探讨是否存在NE从时间的E。大肠杆菌O 157：H7污染的NE丰富的食物内感染的肠道可能是一个因素介导的出血性结肠炎的发展。实验结果表明，NE对E.大肠杆菌O 157：H7污染的NE丰富的食物内感染的肠道可能是一个因素介导的出血性结肠炎的发展。实验结果表明，NE对E.大肠杆菌O 157：H7的生长是由于产生了一种生长的自诱导物。因此，我们的具体目标是：1）确定一个纯化的饮食补充水平的NE在常见的污染的食物中发现的“启动”E的能力。coli O 157：H7对胃肠道系统内NE富集环境的适应能力; coliO 157：H7，因为应激和对照动物之间NE管腔水平的差异将提供对应激改变结肠炎易感性的公认能力的更好理解;大肠杆菌O 157：H7体外暴露于NE补充饲料的对照组; 5）研究胃肠道内NE释放的阻断是否可以改变对E. coli P157：H7; 6）纯化NE诱导的E.大肠杆菌O 157：H7生长自诱导因子的研究，并确定其结构，这可能为开发特异性中断细菌分裂的药物以及鉴定参与其产生的基因提供基础。总的来说，上述目标将寻求建立一个直接的因果关系之间的NE含量的食物和胃肠道的trat影响的能力，E。大肠杆菌O 157：H7引起感染。神经内分泌与细菌的直接相互作用是大肠杆菌致病机制之一。大肠杆菌O 157：H7感染可能会产生新的治疗方法，用于预防和治疗出血性结肠炎。