Aetokthonotoxin (AETX) aka ‘eagle toxin’ discovered in 2021
Aetokthonotoxin (AETX), colloquially ‘eagle toxin’, was discovered in 2021 as the cyanobacterial neurotoxin causing vacuolar myelinopathy (VM) in eagles in North America.
Clinical signs have been recorded from research studies where individual birds were intentionally given the disease and from wild specimens and dead birds recovered from the field.
Raptors have been seen flying into objects, such as trees and rock faces
Waterfowl swim awkwardly, sometimes on their backs
Lack of coordination in flying and walking, sometimes dragging wings or one leg
Waterfowl crash land into water
Tremors of the head
Weight loss
Unresponsiveness to noise
Limb weakness
Beak and tongue weakness
Decreased pain response
Fischer, J. R.; Lewis-Weis, L. A.; Tate, C. M (2003). “Experimental vacuolar myelinopathy in red-tailed hawks”. Journal of Wildlife Diseases. 39 (2): 400–406. doi:10.7589/0090-3558-39.2.400.
Wilde, S. B.; T. M. Murphy; C. P. Hope; S. K. Habrun; J. Kempton; A. Birrenkott; F. Wiley; W. W. Bowerman; J. Lewitus (2005). “Avian vacuolar myelinopathy linked to exotic aquatic plants and a novel cyanobacterial species”. Environmental Toxicology: 348–353. doi:10.1002/tox.20111.
Larsen, R. S.; F. B. Nutter; T. Augspurger; T. E. Rocke; L. Tomlinson; N. J. Thomas; M. K. Stoskopf (2002). “Clinical features of avian vacuolar myelinopathy in American coots”. Journal of the American Veterinary Medical Association. 221 (1): 80–85. doi:10.2460/javma.2002.221.80.
As the biosynthesis of aetokthonotoxin depends on the availability of bromide in freshwater systems and requires an interplay between the toxin-producing cyanobacterium Aetokthonos hydrillicola and the host plant it epiphytically grows on (most importantly hydrilla), it took > 25 years to discover aetokthonotoxin as the VM-inducing toxin after the disease has first been diagnosed in bald eagles in 1994.
Wilde, S. B.; T. M. Murphy; C. P. Hope; S. K. Habrun; J. Kempton; A. Birrenkott; F. Wiley; W. W. Bowerman; J. Lewitus (2005). “Avian vacuolar myelinopathy linked to exotic aquatic plants and a novel cyanobacterial species”. Environmental Toxicology: 348–353. doi:10.1002/tox.20111.
The toxin cascades through the food-chain: Among other animals, it affects fish and waterfowl such as coots or ducks which feed on hydrilla colonized with the cyanobacterium. Aetokthonotoxin is transmitted to raptors, such as the bald eagle, that prey on these affected animals.
The total synthesis of AETX has been achieved in 2021, the enzymatic functions of the 5 enzymes involved in AETX biosynthesis were described in 2022.
Manuel G. Ricardo, Markus Schwark, Dayma Llanes, Timo H. J. Niedermeyer, Bernhard Westermann (2021-06-03), “Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy”, Chemistry – A European Journal (in German), vol. 27, no. 47, pp. 12032–12035, doi:10.1002/chem.202101848, PMC8453946, PMID34081364
Birrenkott et al. (2004) attempted a study in 2004 to determine linkage between the invasive aquatic plant Hydrilla verticillata and the outbreak of AVM among waterfowl after it was observed that only lakes containing excess amounts of hydrilla harbored infected birds. In this study, adult mallards and northern bobwhites were divided by species into multiple sections to observe the effects of hydrilla when it was ingested by the birds, and also by physical contact or drinking of water containing hydrilla. The results of this study found that drinking water or physical contact with hydrilla or areas in which it was present had no noticeable effect on test birds. However, when fed a diet of over 50% hydrilla, the birds developed AVM. Wilde et al. (2005) performed a study to determine the cause of AVM by conducting food trials in areas affected by AVM. Disease-free mallards were fed cyanobacteria from hydrilla and observed daily. Birds that developed symptoms were captured and euthanized. By the conclusion of the study, 15 of the 20 study mallards had been recovered, and all had AVM. In 2021, after 25 years of research on this disease, it’s cause was finally identified to be a novel tryptophan derived alkaloid known as Aetokthonotoxin that is produced by the aforementioned bacteria.
Wilde, S. B.; T. M. Murphy; C. P. Hope; S. K. Habrun; J. Kempton; A. Birrenkott; F. Wiley; W. W. Bowerman; J. Lewitus (2005). “Avian vacuolar myelinopathy linked to exotic aquatic plants and a novel cyanobacterial species”. Environmental Toxicology: 348–353. doi:10.1002/tox.20111.
Manuel G. Ricardo, Markus Schwark, Dayma Llanes, Timo H. J. Niedermeyer, Bernhard Westermann (2021-06-03), “Total Synthesis of Aetokthonotoxin, the Cyanobacterial Neurotoxin Causing Vacuolar Myelinopathy”, Chemistry – A European Journal (in German), vol. 27, no. 47, pp. 12032–12035, doi:10.1002/chem.202101848, PMC8453946, PMID34081364
Wilde, S. B.; T. M. Murphy; C. P. Hope; S. K. Habrun; J. Kempton; A. Birrenkott; F. Wiley; W. W. Bowerman; J. Lewitus (2005). “Avian vacuolar myelinopathy linked to exotic aquatic plants and a novel cyanobacterial species”. Environmental Toxicology: 348–353. doi:10.1002/tox.20111.
