Double Trouble: Infamous “Eagle Killer” Bacterium Produces Not One, But Two Potent Toxins

What is it about?

The cyanobacterium Aetokthonos hydrillicola produces not just one, but two highly potent toxins. An international team led by Martin Luther University Halle-Wittenberg (MLU), Freie Universität Berlin and the Czech Academy of Sciences describes the second toxin, which had remained elusive until now. Even in low concentrations, it can destroy cells and is similar to substances currently used in cancer treatment. Two years ago, the same team established that the first toxin from the cyanobacterium is the cause of a mysterious disease among bald eagles in the USA. Aetokthonos hydrillicola is particularly challenging for researchers. It is notoriously difficult to cultivate and produces one of its toxins only under specific conditions. The fact that it produces two toxins with very different chemical makeups is also unusual. Cyanobacteria normally produce only one toxin – and A. hydrillicola was established as the source of aetokthonotoxin in 2021. This discovery was made by Professor Susan Wilde from the University of Georgia (USA) and Professor Timo Niedermeyer, who worked at MLU until July 2023 and has now joined the researchers at Freie Universität Berlin. This toxin solved a riddle that had kept scientists busy for decades: it triggers the disease vacuolar myelinopathy (VM) among bald eagles in the United States. VM causes holes to form in the brain and, as a result, the birds lose control of their bodies. Science ran the breakthrough as a cover story at the time, and the international team picked up several awards for its work. Markus Schwark from MLU was able to provide evidence of the second, previously unknown toxin and characterized the compound in detail. “We were very surprised when we worked out the structure of this toxin. It resembles toxins that have been found in marine cyanobacteria. They are even already being used in cancer-cell killing drugs,” says Schwark. Based on the bacterium and the similar, known toxins, the researchers have named the newly discovered toxin “aetokthonostatin.” Scientists have suspected that this toxin exists for some time: “During one of our first investigations over ten years ago, we discovered that an extract of the cyanobacterium is highly toxic for cells. We assumed that this effect points to aetokthonotoxin that triggers the avian disease,” says Timo Niedermeyer. However, further examinations revealed that the bird toxin only causes minor direct cell damage. Extracts with zero aetokthonotoxin content still destroyed cells even in extremely low concentrations. So Aetokthonos hydrillicola had to be producing another very powerful toxin. A team from the Czech Academy of Sciences led by Dr. Jan Mareš was able to determine which genes in the cyanobacterium are behind the synthesis of the new toxic molecule. Since the compound is similar to substances that are used in antitumor medicine, the findings could help to develop new drugs that fight cancer. The cyanobacterium is also thriving in American lakes and rivers that feed the drinking water network. The scientists therefore recommend monitoring these waters more frequently for Aetokthonos hydrillicola and its two toxins to avoid potential risks to human health. The study was funded by the German Research Foundation (DFG) and the Czech Science Foundation (GAČR).

Featured Image

Photo by Ruben Zavala on Unsplash

Photo by Ruben Zavala on Unsplash

Why is it important?

Cyanotoxins have adverse effects on ecosystems. Our understanding of their potential risk has recently been expanded by the discovery of aetokthonotoxin, produced by the cyanobacterium Aetokthonos hydrillicola growing on invasive plants. Via trophic transfer, it acts as a neurotoxin causing mortality in animals including top predators like bald eagles. Closer examination of A. hydrillicola revealed that it also produces highly toxic dolastatin derivatives. A. hydrillicola is the only known cultured cyanobacterium producing dolastatin derivatives, which allowed uncovering biosynthetic gene clusters of this compound family. In contrast to all other known dolastatin producers, which are marine cyanobacteria, A. hydrillicola thrives in freshwater reservoirs, making it a potential threat also for human health. Monitoring of the cyanobacterium and its toxins is strongly recommended.