Deadly mushroom toxin exposed

Researchers have isolated and identified a muscle-destroying compound

A toadstool toxin that spurs convulsions, nausea, impaired speech and muscle stiffness — and has led to several deaths in Japan in recent years — has been isolated and identified by a team of scientists. The small molecule is familiar to synthetic chemists but had never been isolated from a natural source, researchers report online May 24 in Nature Chemical Biology.

MUSCLE POISON When ingested, the lethal toxin of Russula subnigricans mushrooms leads to the breakdown of muscle tissue, a mode of poisoning that is unusual in the mushroom world. Kimiko Hashimoto

Acute poisoning that leads to a breakdown of skeletal muscle tissue — a syndrome known as rhabdomyolysis — is not often caused by a mushroom and is quite different from the effects of toxins produced by Amanita species, says Petteri Nieminen, a specialist in physiology and toxicology at the University of Joensuu in Finland. Amanita mushrooms, including the notorious death cap and death angel, bear the toxins that are responsible for more than 90 percent of mushroom-caused fatalities.

The toxic nature of Russula subnigricans, the species addressed in the new study, has been on the margins of mushroom research, Nieminen said. The new work “might bring this type of poisoning more to the foreground of mushroom studies,” he says. “That would be a nice thing.” Many fungi that produce toxins also produce beneficial compounds that warrant investigation as therapeutics, Nieminen notes.

Led by Kimiko Hashimoto of Kyoto Pharmaceutical University and Masaya Nakata of Keio University in Yokohama, Japan, the researchers first isolated the toxin, a difficult task because the compound likes to bind to other things. Various spectroscopic analyses established the toxin’s structure: a small, 4-carbon molecule known as cycloprop-2-ene carboxylic acid. Previously unknown in the natural world, the toxin and its derivatives are used for building other compounds in synthetic chemistry, the researchers note.

Identifying the mushroom’s toxic compounds took some detective work, Hashimoto says. Previous work on mushrooms thought to be R. subnigricans from the Miyagi prefecture in northeast Japan isolated toxic compounds dubbed russuphelins, but the research team found the compounds had no effect on mice. This suggests these northeast mushrooms should be renamed as a different species. The team then turned to the R. subnigricans growing in the Kyoto region, where several of the poisonings occurred. These mushrooms were lethal to mice, bringing about the unusual rhabdomyolysis when ingested. The isolated compound spurred the same result.

An additional symptom of rhabdomyolysis is the presence of myoglobin — the oxygen-carrying protein of muscle cells — in the urine. Myoglobin breaks down into potentially harmful compounds and can mess with the kidneys. The specific reactions triggered by R. subnigricans’ toxin that lead to these symptoms are the subject of future work, Hashimoto says.

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