Vacuolar myelinopathy is a fatal neurological disease that was initially discovered during a mysterious mass mortality of bald eagles in Arkansas in the United States. The cause of this wildlife disease has eluded scientists for decades while its occurrence has continued to spread throughout freshwater reservoirs in the southeastern United States. Recent studies have demonstrated that vacuolar myelinopathy is induced by consumption of the epiphytic cyanobacterial species Aetokthonos hydrillicola growing on aquatic vegetation, primarily the invasive Hydrilla verticillata. Here, we describe the identification, biosynthetic gene cluster, and biological activity of aetokthonotoxin, a pentabrominated biindole alkaloid that is produced by the cyanobacterium A. hydrillicola. We identify this cyanobacterial neurotoxin as the causal agent of vacuolar myelinopathy and discuss environmental factors—especially bromide availability—that promote toxin production.

空泡性髓鞘病是一种致命的神经系统疾病，最初是在美国阿肯色州秃鹰神秘大规模死亡事件中发现的。这种野生动物疾病的病因几十年来一直困扰着科学家，而它的发生却继续在美国东南部的淡水水库中蔓延。最近的研究表明，空泡性脊髓病是由于消耗了生长在水生植物（主要是入侵性轮叶黑藻）上的附生蓝藻Aetokthonos Hydrillicola而引起的。在这里，我们描述了蓝藻毒素（一种由蓝藻A. Hydrillicola产生的五溴化双吲哚生物碱）的鉴定、生物合成基因簇和生物活性。我们将这种蓝藻神经毒素确定为空泡性脊髓病的致病因子，并讨论了促进毒素产生的环境因素，尤其是溴化物的有效性。