Zebrafish Embryos as a Model for Cyanobacterial Toxins

斑马鱼胚胎作为蓝藻毒素的模型

• 批准号: 7097701
• 负责人: JOHN P BERRY
• 金额: $ 2.11万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2006-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097701
• 关键词: Cyanophyta; bacterial toxins; bioaccumulation; biological models; biomarker; detoxification; embryo /fetus toxicology; environmental toxicology; enzyme activity; fresh water environment; heavy metals; lipopolysaccharides; mercury; messenger RNA; metallothionein; microorganism culture; nonmammalian vertebrate embryology; nucleic acid quantitation /detection; sample collection; toxicant interaction; toxicant screening; toxin metabolism; water microbiology; zebrafish

DESCRIPTION (provided by applicant): Cyanobacteria, or "blue-green algae," particularly in freshwater habitats, are recognized to produce an array of potently toxic compounds. Growing evidence indicates that toxigenic cyanobacteria represent a serious concern to human and environmental health. Development of novel approaches will be key to understanding both current and emerging roles of cyanobacterial toxins in environmental health. The proposed research will utilize the zebrafish (Danio rerio) embryo as a toxicological model to investigate toxic or otherwise bioactive metabolites from cyanobacteria. This research will isolate and culture cyanobacteria from two, ecologically unique and distinct freshwater microbial communities, namely the Florida Everglades (and associated waterways in South Florida) and the northern Great Lakes. Cyanobacterial isolates will be screened using the zebrafish embryo as a model of vertebrate development specifically to identify metabolites which interfere with developmental pathways (i.e. developmental toxins). The bioassay will be further utilized to guide initial purification of identified toxins toward the goal of chemical and biological characterization of potentially novel compounds. In addition, the zebrafish model will be used specifically to investigate a ubiquitous class of bacterial toxins, the lipopolysaccharides (LPSs), from cyanobacteria. Though LPSs (or "endotoxins") from Gram-negative heterotophic eubacteria are well described, the same compounds from cyanobacteria have been largely unexplored. However, emerging evidence indicates that cyanobacterial LPSs may have specific effects on certain "detoxifying enzymes," and a subsequent interactive effects with other toxins. Accordingly, the proposed research will further utilize the zebrafish embryo model to test several hypothesis related to the effects of LPSs, specifically from isolated strains of Microcystis, on heavy metal toxicity and accumulation. The proposed research will contribute significantly to our growing understanding of the role of freshwater cyanobacterial toxins in environmental health.

描述（由申请人提供）：蓝细菌或“蓝绿色藻类”，特别是在淡水栖息地中，被认为会产生一系列有效的有毒化合物。越来越多的证据表明，毒蓝细菌代表了人类和环境健康的严重关注。新方法的发展将是了解蓝细菌毒素在环境健康中的当前和新兴作用的关键。拟议的研究将利用斑马鱼（Danio Rerio）胚胎作为一种毒理学模型，以研究蓝细菌的毒性或生物活性代谢产物。这项研究将与两个在生态独特且独特的淡水微生物群落中分离出和培养蓝细菌，即佛罗里达大沼泽地（以及南佛罗里达州的相关水道）和北部大湖区。蓝细菌分离株将使用斑马鱼胚胎作为脊椎动物发育的模型进行筛选，以识别干扰发育途径（即发育性毒素）的代谢产物。该生物测定将进一步用于指导鉴定毒素的初始纯化，以实现潜在新颖化合物的化学和生物学特征的目标。此外，斑马鱼模型将专门用于研究来自蓝细菌的普遍存在的细菌毒素，脂多糖（LPS）。尽管革兰氏阴性异噬细胞菌的LPSS（或“内毒素”）被很好地描述了，但蓝细菌的相同化合物在很大程度上尚未探索。然而，新兴的证据表明，蓝细菌LPS可能对某些“排毒酶”具有特定的影响，并与其他毒素产生互动作用。因此，拟议的研究将进一步利用斑马鱼胚胎模型来检验与LPS（特别是从微囊菌株）对重金属毒性和积累的孤立菌株相关的几种假设。拟议的研究将对我们对淡水蓝细菌毒素在环境健康中的作用的不断理解产生重大贡献。