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

描述（由申请人提供）：霍乱是一种严重的腹泻疾病，由一种革兰氏阴性细菌霍乱弧菌引起，有可能通过污染水和食物供应而被用作生物恐怖武器。美国国立过敏症和传染病研究所（NIAID）将霍乱弧菌列为具有潜在生物恐怖威胁的“B”类病原体。溶血磷脂酸（LPA）是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，有助于减轻炎症性肠病和腹泻患者的体重减轻。我们将提供初步数据表明，LPA给药可显著减少小鼠霍乱毒素（CTX）诱导的肠液分泌。在此基础上，本研究将验证富含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的假设。因此，除了口服补液治疗外，使用脂质介质如LPA及其类似物对治疗霍乱弧菌大流行有价值。

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.