Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy

Abstract

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.

Cyanobacteria and Cyanotoxins in a Changing Environment: Concepts, Controversies, Challenges

“…An example of a recently discovered toxin with (yet) regionally limited occurrence is aetokthonotoxin, a polybrominated tryptophane derivative that is suspected to be the cause of the death of bald eagles and water birds in the United States [211]. Brominated metabolites are known primarily from marine cyanobacteria [212] while halogenated metabolites in freshwater cyanobacteria are generally chlorinated [213].…”

Cyanotoxins and the Nervous System

“…The disease was associated with exposure to Hydrilla , and epiphytic cyanobacteria present on the surface of this plant were considered as potential causative agents [ 73 ]. Feeding test animals extracts of certain collections of Hydrilla resulted in gross pathology consistent with AVM, and epiphytic cyanobacteria were also shown to be toxic to bird species such as coots that were fed these extracts [ 74 ]. Extensive research has now identified a brominated cyanobacterial toxin, aetokthonotoxin, which results in the production of vacuoles and lesions in the brains of birds fed this toxin, consistent with it being a cause of AVM [ 74 ].…”

Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy

“…Aetokthonotoxin (AETX) is a pentabrominated biindole alkaloid produced by the cyanobacterium Aetokthonos hydrillicola , which grows epiphytically on an invasive plant, Hydrilla verticillata , in freshwater lakes [1] . The toxin traverses the food chain from animals consuming the plant (and thus also the cyanobacterium) like waterfowl or snails and then on to raptors such as eagles (e. g. American bald eagle) and kites.…”

“…The toxin traverses the food chain from animals consuming the plant (and thus also the cyanobacterium) like waterfowl or snails and then on to raptors such as eagles (e. g. American bald eagle) and kites. While the mode‐of‐action of AETX is still unknown, it has been shown to elicit Vacuolar Myelinopathy in birds, which is characterized by a widespread vacuolization of the myelinated axons in the white matter of the brain and spinal cord of affected animals [1] . AETX has also been found to be highly toxic to the nematode C. elegans (LC 50 40 nM), [1] but susceptibility of mammals to this toxin has not been studied, yet.…”