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

雪卡特拉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，这些珊瑚鱼通过海洋食物网积累了毒素。由甲藻产生的脂溶雪卡毒素被草食性鱼类消耗，开始食物网生物放大和生物转化的过程，最终导致人类。据不同的估计，雪卡特拉中毒的频率为每年50万例，来自不同太平洋当地人的记录表明，超过90%的人类鱼类中毒是由雪卡特拉引起的。雪卡是美国严重的公共健康威胁，据估计，它占有害藻华相关医疗费用的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，雪卡特拉影响人类和生态系统健康。尽管雪卡特拉有着悠久的历史和数十年的研究，但控制雪卡特拉疫情的因素却知之甚少。这在很大程度上是由于雪卡毒素的复杂分子结构，产生临床症状的微小剂量，以及确定分析所需的强大分析化学。人类和/或自然引起的海洋扰动、高毒力菌株的繁殖，都被假设为雪卡特拉病毒频率和症状的地理差异的原因因素。特别是对于冈比亚圆盘藻来源毒素的差异，人们知之甚少。以及它们对雪卡毒素同系物后续生物转化的影响；这是本次合作研究的重点。利用这笔小额探索性研究赠款的资金，四家美国机构的研究人员将进行探索性研究，以解决一个基本问题：来自大西洋(墨西哥湾和加勒比海)和太平洋盆地的不同物种和菌株的冈比亚鱼产出的雪卡毒素是否相同？尽管疾病的严重性、影响和全球分布，这个问题从未得到回答，尽管有大量关于其他不太严重的HAB毒素的信息。这一结果将为今后研究雪卡毒素的流行病学、毒素转移和修饰以及动态变化提供基础信息。这一问题将由德克萨斯大学奥斯汀分校、夏威夷大学S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(阿拉巴马州多芬岛)和NOAA天然产品中心(南卡罗来纳州查尔斯顿)共同努力解决。这项研究的主要目标是确定从这些不同地区分离的冈比亚圆盘吸虫菌株中钠通道毒素(雪卡毒素)的质量是否相同或不同。第二个目标是确定不同物种或菌株的主要和次要钠通道毒素的特征是否不同。该项目将在这一困难领域获得前所未有的分析确认，并将为未来涉及这些毒素的工作提供坚实的基础。除了对公众健康明显的更广泛的影响外，该项目还将支持两名理科硕士研究生(德克萨斯州大学和夏威夷大学)，其中一人将在FDA实验室接受毒素生物分析技术方面的培训。结果将在国家会议上提出，并通过同行评议的出版物向科学界传播。所使用的技术将为这一领域的未来研究人员提供一个标准的和经过测试的方案，并将引起赤潮毒素研究人员的普遍兴趣。

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.