Vibrio Cholerae as a bioterror agent: New means of treating a potential pandemic

霍乱弧菌作为生物恐怖剂：治疗潜在大流行的新方法

• 批准号: 7364575
• 负责人: Anjaparavanda P Naren
• 金额: $ 7.16万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7364575
• 关键词: Agonist; Bioterrorism; Blood; Body Weight decreased; Cabbage - dietary; Categories; Cholera; Cholera Toxin; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Diarrhea; Disease; Egg White; Exhibits; Fluids and Secretions; Food; Food Supply; Gastrointestinal tract structure; Glycine max; Goals; Gram-Negative Bacteria; Inflammatory Bowel Diseases; Intestines; Lecithin; Lysophosphatidic Acid Receptors; Lysophospholipids; Methods; Mus; National Institute of Allergy and Infectious Disease; New Agents; Oral Rehydration Therapy; Pharmaceutical Preparations; Property; Reagent; Research; Resistance; Soybeans; Testing; Therapeutic; Vibrio cholerae; Water; Water Supply; base; concept; inhibitor/antagonist; lipid mediator; lipid phosphate phosphatase; lysophosphatidic acid; pandemic disease; pathogen

DESCRIPTION (provided by applicant): Cholera is a serious diarrheal disease and is caused by Vibrio cholerae a gram negative bacterium and has the potential to be used as a bioterror weapon by contaminating water and food supplies. The National Institute of Allergy and Infectious Diseases (NIAID) has categorized V. cholerae as category "B" pathogen that posses a potential bioterrorism threat. Lysophosphatidic acid (LPA) is a lipid mediator present in blood and foods. LPA has been shown to be an LPA-receptor agonist and is beneficial in reducing weight loss in inflammatory bowel disease and diarrhea. We will provide preliminary data to show that intestinal fluid secretion induced by cholerae toxin (CTX) in mice is significantly reduced by LPA administration. Based on this observation, the proposed research will test the hypothesis that foods rich in LPA and stabilized synthetic LPA-receptor agonists can inhibit CTX-induced secretory diarrhea in mice. Therefore the use of lipid mediators such as LPA and its anologs in addition to oral rehydration therapy would have value in treating V. cholerae pandemic. The specific aims of this proposal are: Aim 1: To test if foods rich in LPA will inhibit CTX-induced diarrhea in mice. Aim 2: To test if metabolically stabilized synthetic LPA-receptor agonists exhibit potent anti- diarrheal properties (compared to LPA). These studies will demonstrate that cholera toxin-induced diarrhea can be controlled by consuming foods rich in LPA. It will also help us test and develop drugs that may have therapeutic potential. It will help move us toward the long-term goal of understanding the lipid mediators which (e.g., LPA) can regulate the CFTR Cl- channel function. The results of these studies will provide us with possible alternative methods of treating diseases of the gastrointestinal tract such as secretory diarrhea, that can be caused due to an act of bioterror such as contaminating food and water supplies with V. cholerae or due to natural causes.

描述(申请人提供)：霍乱是一种严重的腹泻疾病，由霍乱弧菌引起，霍乱是一种革兰氏阴性细菌，有可能被用作生物恐怖武器，污染水和食物供应。美国国家过敏和传染病研究所(NIAID)已将霍乱弧菌归类为具有潜在生物恐怖主义威胁的B类病原体。溶血磷脂酸(LPA)是一种存在于血液和食物中的脂质介质。LPA已被证明是一种LPA受体激动剂，在炎症性肠病和腹泻中有助于减轻体重减轻。我们将提供初步数据显示，给予LPA可显著减少霍乱毒素(CTX)诱导的小鼠肠液分泌。基于这一观察，拟议的研究将检验这样的假设，即富含LPA和稳定的合成LPA受体激动剂的食物可以抑制CTX诱导的小鼠分泌性腹泻。因此，在口服补液治疗的基础上使用脂类介体，如LPA及其类似物，对霍乱弧菌大流行有一定的治疗价值。 这项建议的具体目标是： 目的1：检测富含LPA的食物是否能抑制环磷酰胺所致的小鼠腹泻。 目的2：测试代谢稳定的合成LPA受体激动剂是否表现出有效的止泻特性(与LPA相比)。 这些研究将证明，霍乱毒素引起的腹泻可以通过食用富含LPA的食物来控制。它还将帮助我们测试和开发可能具有治疗潜力的药物。这将有助于我们朝着了解脂质介质(例如，LPA)可以调节CFTRCl-通道功能的长期目标前进。这些研究的结果将为我们提供可能的替代方法来治疗胃肠道疾病，如分泌性腹泻，这些疾病可由生物恐怖行为引起，如霍乱弧菌污染食物和水供应，或由自然原因引起。