SGER: Preliminary characterization of sodium channel toxins in Gambierdiscus spp. from the Pacific and Atlantic Oceans

雪卡毒是世界上最常见的海鲜中毒。人类通过食用珊瑚鱼获得雪卡毒素，珊瑚鱼通过海洋食物网积累了毒素。脂溶性雪卡毒素由甲藻Gamberiduscus toxicus产生，被食草鱼类消耗，开始了食物网生物放大和生物转化的过程，最终导致人类。据各种估计，每年发生50万起雪卡毒事件，太平洋当地人的记录表明，超过90%的人类鱼类中毒是由于雪卡毒。对美国公众健康的严重威胁，据估计，雪卡毒素占与有害藻华有关的医疗费用的95%。由于这些毒素也可能直接影响鱼类，改变行为，并可能损害免疫反应，雪卡毒素影响人类和生态系统的健康。尽管雪卡毒素的历史悠久，研究数十年，控制雪卡毒素爆发的因素知之甚少。这在很大程度上是由于雪卡毒素的复杂分子结构、产生临床病理学的微小剂量以及确定性分析所需的强大分析化学。G.毒素、人类和/或自然引起的海洋扰动，都被假设为雪卡毒频率和生态学地理变异的原因。特别是很少有人知道的差异，在源毒素从Gambierdiscus属。以及它们对雪卡毒素同系物随后的生物转化的影响;这是这项合作研究的重点。通过这项探索性研究小额赠款的资助，美国四个机构的研究人员将进行探索性研究，解决一个基本问题：大西洋（墨西哥湾和加勒比海）和太平洋盆地的物种和菌株之间冈比亚盘鱼产生的雪卡毒素是否相同？尽管疾病的严重性，影响和全球分布，这个问题从来没有得到回答，虽然有丰富的信息，其他严重程度较低的赤潮毒素。研究结果将为进一步研究雪卡毒的流行病学、毒素转移和变异以及动态提供基础资料。这个问题将由德克萨斯大学奥斯汀分校和夏威夷大学？美国海洋与人类健康中心（太平洋海洋生物医学研究中心）、FDA海鲜安全实验室（亚拉巴马多芬岛）和NOAA天然产品中心（南卡罗来纳州查尔斯顿）。研究的主要目的是确定从这些不同地区分离的甘比盘菌菌株中钠通道毒素（雪卡毒素）的质量是否相同或不同。第二个目标是确定优势和次级钠通道毒素的谱在物种或菌株之间是否不同。该项目将在这一困难领域进行前所未有的分析确认，并将为今后涉及这些毒素的工作奠定坚实的基础。除了对公共卫生产生明显的广泛影响外，该项目还将支持两个硕士学位。研究生（德克萨斯大学和夏威夷大学），其中一人将在FDA实验室接受毒素生物测定技术培训。研究结果将在国家会议上介绍，并通过同行评审的出版物向科学界传播。所使用的技术将提供一个标准和测试的协议，为未来的研究人员在这一领域，并会感兴趣的赤潮毒素研究人员一般。

Ciguatera is the most common seafood intoxication in the world. Humans acquire ciguatoxin by eating reef fish that have accumulated the toxins via the marine food web. Lipid-soluble ciguatoxins produced by the dinoflagellate Gamberiduscus toxicus are consumed by herbivorous fish, beginning the processes of foodweb biomagnification and biotransformation that ultimately leads to humans. The frequency of ciguatera is variously estimated to be 500,000 cases per year, and records from various Pacific locals suggest that over 90% of human fish poisonings are due to ciguatera. A serious public health threat in the U.S., ciguatera is estimated to account for 95% of medical costs associated with harmful algal blooms. Because these toxins may also affect fish directly, altering behavior and possibly compromising immune responses, ciguatera impacts both human and ecosystem health.Despite its long history and decades of research, the factors controlling ciguatera outbreaks are poorly understood. This is due in no small part to the complex molecular structure of ciguatoxin, the minute doses that produce clinical symptomology, and the robust analytical chemistry required for definitive analyses. Proliferation of high-potency strains of G. toxicus, human and/or naturally-induced oceanographic perturbations, have all been hypothesized as causative factors explanations for geographic variability in ciguatera frequency and symptomology. Exceptionally little is known about differences in the source toxins from Gambierdiscus spp. and their influence on the subsequent biotransformation of ciguatoxin congeners; this is the focus of this collaborative research. With funding through this Small Grant for Exploratory Research, researchers at four U.S. institutions will undertake exploratory research addressing a basic question: Are the ciguatoxins produced by Gambierdiscus the same across species and strains from the Atlantic (Gulf of Mexico and Caribbean) and the Pacific Ocean basins? Despite the severity, impact, and global distribution of the illness, this question has never been answered, although there is abundant information on other, less severe HAB toxins. The results should provide foundation information for future studies examining epidemiology, toxin transfer and modification, and dynamics of ciguatera. The problem will be addressed by a collaborative effort between The University of Texas at Austin, the University of Hawaii?s Center for Oceans and Human Health (Pacific Marine Biomedical Research Center), the FDA Seafood Safety laboratory (Dauphin Island, Alabama) and NOAA Natural Products Center (Charleston, SC). The primary goal of the research is to determine if the mass of the sodium channel toxin (ciguatoxin) is the same or different in Gambierdiscus strains isolated from these different areas. The secondary goal is to determine if the profile of dominant and secondary sodium channel toxins differ across species or strains. The project will have an unprecedented degree of analytical confirmation in this difficult field and will provide a solid foundation for future work involving these toxins. Besides the obvious broader impacts for public health, the project will support two M.S. graduate students (UTexas and UHawaii), one of whom will train at the FDA laboratory in the techniques of the toxin bioassay. Results will be presented at national meetings and disseminated to the scientific community via peer-reviewed publications. The techniques used will provide a standard and tested protocol for future researchers in this area and will be of interest to HAB toxin researchers in general.