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

雪卡泰是世界上最常见的海鲜中毒。人类通过食用通过海洋食物网积累毒素的珊瑚鱼而获得雪卡毒素。脂溶性雪卡毒素由甲酰鞭毛藻Gamberiduscus toxicus产生，被草食性鱼类消耗，开始食物网的生物放大和生物转化过程，最终导致人类。据估计，雪卡毒素中毒的频率为每年50万例，而太平洋各地的记录显示，超过90%的人类鱼类中毒是由雪卡毒素引起的。在美国，雪卡毒素是一种严重的公共健康威胁，据估计，与有害藻华有关的医疗费用中有95%是由雪卡毒素造成的。因为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。尽管有悠久的历史和几十年的研究，控制雪卡水爆发的因素却知之甚少。这在很大程度上是由于雪卡托毒素复杂的分子结构，产生临床症状的微小剂量，以及确定分析所需的强大分析化学。毒杆菌高效菌株的增殖、人为和/或自然引起的海洋扰动，都被假设为解释雪卡中毒频率和症状的地理差异的致病因素。冈比亚赤藓属源毒素的差异及其对随后的雪卡毒素同源物的生物转化的影响所知甚少；这是本次合作研究的重点。在探索性研究小额赠款的资助下，四个美国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）和太平洋盆地的冈比亚铁鱼产生的雪卡毒素在不同物种和菌株之间是否相同？尽管该疾病的严重性、影响和全球分布，但这个问题从未得到回答，尽管有大量关于其他较不严重的HAB毒素的信息。研究结果可为今后研究雪卡毒素的流行病学、毒素转移和修饰、动态等提供基础资料。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）、美国食品药品监督管理局海鲜安全实验室（阿拉巴马州多芬岛）和美国国家海洋和大气管理局天然产品中心（南卡罗来纳州查尔斯顿）。这项研究的主要目的是确定从这些不同地区分离的冈比亚铁cus菌株中钠通道毒素（雪卡毒素）的质量是相同的还是不同的。第二个目标是确定是否优势和次级钠通道毒素的轮廓不同物种或菌株。该项目将在这一困难领域获得前所未有的分析确认，并将为今后涉及这些毒素的工作提供坚实的基础。除了对公共卫生产生明显的广泛影响外，该项目还将支持两名硕士研究生（德克萨斯州和夏威夷大学），其中一人将在FDA实验室接受毒素生物测定技术的培训。研究结果将在国家会议上公布，并通过同行评议的出版物向科学界传播。所使用的技术将为该领域的未来研究人员提供一个标准和经过测试的方案，并将引起一般有害藻毒素研究人员的兴趣。

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.