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Antidote Discovered for Lethal “Death Cap” Mushroom Poisoning

A death cap mushroom seen in woodland.
A death cap mushroom. Credit: iStock
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A new study has shown that a commonly used medical dye acts as an antidote for poisoning by the “death cap” mushroom, Amanita phalloides. The death cap is thought to be responsible for 90% of mushroom-linked fatalities each year. The research is published in Nature Communications.

No fun with fungi

Mushroom poisoning is a global issue that is thought to kill hundreds of people worldwide each year. Death cap mushrooms account for more than 90% of those deaths. Unsurprisingly, mushroom poisoning is a greater threat in cultures where the consumption of wild mushrooms is more commonplace. In China, nearly 40,000 illnesses and 800 deaths were recorded between 2010 and 2020.  

People mistakenly consuming death cap mushrooms are exposed to amatoxins, a toxic agent that is not destroyed by cooking. Once absorbed by our gastrointestinal tract, amatoxin is absorbed by our liver, which causes cells to die leading to organ failure and death.

There’s currently no antidote to amatoxin poisoning, but this paper may change that. Researchers at Sun Yat-sen University in Guangzhou scanned potential molecular targets that might be able to inhibit amatoxin. They did this using two screening methods. First, they used the gene-editing tool CRISPR to identify the genes that are implicated in the death of cells in the liver. This analysis identified that a protein called STT3B – which is involved in the biologically important N-glycan biosynthesis pathway – is required to elicit amatoxin’s deadly effects.

They then leafed through a library of drugs approved by the US Food and Drug Administration to mark out those that could inhibit STT3B, turning up indocyanine green (ICG). This molecule is a fluorescent iodide dye, which has been used in humans as a diagnostic aid since 1956.

Protective effect

ICG was then tested for its anti-amatoxin potential in human cell lines and in mice. Rodents exposed to amatoxin and then ICG were more than twice as likely to survive than mice only exposed to the toxin. Nevertheless, half of the mice protected with ICG still died from exposure. Furthermore, there is a time limit to the compound’s protection, with results suggesting that it should be injected within the first few hours after mushroom poisoning to elicit an effect. 

The team says in their discussion that more research will be required to identify exactly how ICG works to block the mushroom’s toxicity but suggest that the blockage of the toxin into circulation in the liver is a likely contributing factor.

Reference: Wang B, Wan AH Zhang R et al. Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity. Nat Commun. 2023;14:2241. doi: 10.1038/s41467-023-37714-3