Underestimated diversity of toxins from cyanobacteria

They are more than three billion years old. They were also the first organisms on earth to tap sunlight as a source of energy, thereby essentially inventing photosynthesis. “Cyanobacteria can also cope in nutrient-poor waters and are found all over the world,” says Elisabeth Janssen, research group leader at the Environmental Chemistry Department of the aquatic research institute Eawag.

Tragic incident

Science has known for some time that these tiny organisms, often called blue-green algae, produce toxic substances. For about 20 years now, political and social interest in cyanobacteria has been growing. When they suddenly multiply in a body of water and trigger a bloom, like the cyanobacterium Planktothrix rubescens, bathing is strongly discouraged or forbidden. If dogs drink from the murky water containing certain cyanobacteria, they can even die from it.

Until now, toxicology experts have devoted their greatest attention to a specific class of toxins known as microcystins. “This follows from a particularly severe and tragic incident in 1996, which occurred in the Brazilian city of Caruaru,” write a group of researchers including Janssen in a recently published paper. At that time, the local water supply failed and water had to be trucked in from a nearby water reservoir for the hospital. The fact that this water contained microcystins only became clear after 60 dialysis patients had died.

A whole bouquet of metabolites

As a result, the World Health Organization (WHO) issued guidelines on microcystins, which were extended to three other toxins from cyanobacteria in 2021. But this only regulates a tiny fraction of the substances. After all: “Cyanobacteria produce a whole bouquet of secondary metabolites,” says Janssen. The ecotoxicological risks of this variety of substances are still largely unknown. Now the results of experiments with zebrafish larvae conducted by Janssenʼs and vom Bergʼs teams provide a little more clarity.

“We used cell extracts from two different cyanobacterial strains of the genus Microcystis from Brazil,” says Mariana de Almeida Torres, first author of the scientific publication and a fellow of the Eawag Partnership Programme (see box). One strain was isolated from a natural reserve in the Amazon rainforest. It produces microcystins – unlike the other strain, which was isolated from a wastewater treatment plant in Rio de Janeiro.

Edema around the heart

In fact, the microcystin-producing strain proved to be twice as toxic. Half a microgram of extracted biomass from cyanobacteria per millilitre was enough to kill half the zebrafish larvae within a day. “Such a concentration can typically be found during a mass reproduction of cyanobacteria, known as blooms,” says Janssen. Although the other strain did not contain any of the toxins listed in the WHO guidelines, the cyanobacteria from the sewage treatment plant were also toxic: at a concentration of one microgram of biomass per millilitre, they led to the death of half the zebrafish larvae. When the researchers divided the extracts into different chemical fractions, they found that numerous substances made their own contribution to toxicity. The researchers also determined that they often did not immediately lead to the death of the larvae, but severely impaired their development, for example through edemas around their hearts.

Just like the microcystins, these other toxin classes also have exotic names. They are called cyanopeptolins, nostoginins, microginins and micropeptins – and all belong to the chemical universe of the metabolic products of cyanobacteria, which is only gradually being revealed. “So far, we have compiled more than 2,400 substances in a publicly accessible database,” says Janssen, who coordinates the CyanoMetDB project. “And about 100 new entries are added every year.”

Problem gains importance with global warming

But why do cyanobacteria produce toxins? “Somehow they must derive an advantage from them, because the production of these substances costs cyanobacteria a lot of metabolic energy,” says Janssen. However, the nature of this advantage has not yet been clarified, even though there are many theories, such as that the tiny organisms use the substances as signal molecules and thus communicate chemically with each other, or that the toxins protect them from predators.

In any case, the topic is likely to gain in importance in the future. Due to the warming climate, it is expected that cyanobacteria will bloom more frequently in Swiss lakes. Thatʼs why Janssen is keen to raise public awareness of the problem. The environmental chemist adds: “Compared to pollutants from industry, the toxins from cyanobacteria are more difficult to grasp, because they are metabolic products of living organisms – and accumulate when they multiply and we cannot turn off the source as easily.”