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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.

Avian vacuolar myelinopathy (AVM) is a fatal neurological disease that affects various waterbirds and raptors. It is most common in the bald eagle and American coot, and it is known in the killdeerbuffleheadnorthern shovelerAmerican wigeonCanada goosegreat horned owlmallard, and ring-necked duck. Avian vacuolar myelinopathy is a newly discovered disease that was first identified in the field in 1994 when dead bald eagles were found near DeGray Lake in Arkansas in the United States. Since then, it has spread to four more states and infested multiple aquatic systems including 10 reservoirs. The cause of death is lesions on the brain and spinal cord. 

Clinical signs

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.

  • “Avian vacuolar myelinopathy”. USGS National Wildlife Health Center. Archived from the original on 6 October 2014. Retrieved 24 October 2013.
  • 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.
  • “AVM-Wilde Lab”. AVM-Wilde Lab. Archived from the original on 30 June 2013. Retrieved 24 October 2013.

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.

Research highlights

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.

See also

References

  1. Breinlinger, Steffen; Phillips, Tabitha J.; Haram, Brigette N.; Mareš, Jan; Yerena, José A. Martínez; Hrouzek, Pavel; Sobotka, Roman; Henderson, W. Matthew; Schmieder, Peter; Williams, Susan M.; Lauderdale, James D. (2021-03-26). “Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy”Science371 (6536): eaax9050. doi:10.1126/science.aax9050ISSN 0036-8075PMC 8318203PMID 33766860.
  2. “Avian vacuolar myelinopathy”. USGS National Wildlife Health Center. Archived from the original on 6 October 2014. Retrieved 24 October 2013.
  3. Birrenkott, A. H.; S. B Wilde; J. J. Hains; J. R. Fisher; T. M. Murphy; C. P. Hope; P. G. Parnell; W. W. Bowerman (2004). “Establishing a food-chain link between aquatic plant material and avian vacuolar myelinopathy in mallards (Anas platyrhynchos)”Journal of Wildlife Diseases40 (3): 485–492. doi:10.7589/0090-3558-40.3.485PMID 15465716.
  4. 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.202101848PMC 8453946PMID 34081364
  5. Adak, Sanjoy; Lukowski, April L.; Schäfer, Rebecca J. B.; Moore, Bradley S. (2022-02-10). “From Tryptophan to Toxin: Nature’s Convergent Biosynthetic Strategy to Aetokthonotoxin”Journal of the American Chemical Society. American Chemical Society (ACS). 144 (7): 2861–2866. doi:10.1021/jacs.1c12778ISSN 0002-7863PMC 9004672PMID 35142504S2CID 246702060.
  6. “South Carolina’s Bald Eagles-Disease”. SCDNR. 2010. Retrieved 24 October 2013.
  7. “AVM-Wilde Lab”. AVM-Wilde Lab. Archived from the original on 30 June 2013. Retrieved 24 October 2013.
  8. U.S. Department of the Interior; U.S. Geological Survey (August 2002). “Avian vacuolar myelinopathy: An unexplained neurologic disease” (PDF). Retrieved 24 October 2013.
  9. 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.
Cyanotoxins
Neurotoxins

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