World’s Deadliest Mushroom May Now Have an Antidote

The death cap mushroom (Amanita phalloides), which has been the ‘killer of kings’ for centuries, could be losing its edge. Scientists have found a possible antidote for the deadly mushroom’s toxin.

Growing up to 15 centimetres high, with unassuming tan or yellow-green tops, death caps can taste quite nice, according to people who have accidentally eaten them and survived. But afterwards, the toxin can cause vomiting, seizures, severe liver damage and death. The Roman Emperor Claudius is thought to have died from consuming the mushrooms in AD 54, and so is the Holy Roman Emperor Charles VI, in 1740. Today, hundreds of people die from eating poisonous mushrooms each year, and death caps are responsible for 90% of those fatalities.

Despite their deadly reputation, death caps have kept scientists guessing as to how they kill. But when researchers recently identified a potential antidote, they also zeroed in on the biochemical pathway in humans that’s necessary for the mushrooms’ toxin — called α-amanitin — to enter cells. The antidote, a chemical named indocyanine green, interrupts that pathway. The team reported these findings in Nature Communications on 16 May.

“That’s fantastic,” says Helge Bode, a natural product chemist at the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany. “α-Amanitin really is one of the most dangerous compounds that we have in nature.”

A ‘very modern’ approach

Despite death caps’ long history of poisoning people, physicians have little to offer people who accidentally ingest them, besides supportive care. The area seemed ripe for research, so Qiaoping Wang and Guohui Wan, both drug-development researchers at Sun Yat-sen University in Guangzhou, China, decided to dive in.

The scientists used a method that Wang and others developed a few years ago to find an antidote for jellyfish venom. They first used CRISPR-Cas9 gene-editing technology to create a pool of human cells, each with a mutation in a different gene. They then tested which mutations helped the cells to survive exposure to α-amanitin.

This ‘CRISPR-Cas9 screen’ revealed that cells lacking a functional version of an enzyme called STT3B are able to survive α-amanitin. STT3B is part of a biochemical pathway that adds sugar molecules to proteins. Interrupting this pathway somehow blocks α-amanitin from entering cells, preventing the toxin from fully wreaking havoc. Nobody had any idea that STT3B played a…