This Deadly Shellfish Poisoning Has No Antidote. A Protein Found in American Bullfrogs Could Change That
A study in mice found that a protein called saxiphilin acts like a sponge against a deadly toxin produced by algal blooms. The harmful agent, which accumulates in certain seafood, can cause a life-threatening illness called paralytic shellfish poisoning
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Each summer, warm weather and sunlight drive algae growth in ocean waters worldwide. But when the organisms grow out of control, they can transform into harmful “red tide” algal blooms that produce saxitoxin, a deadly substance that affects animals’ nervous systems.
Saxitoxin can accumulate in shellfish and cause a life-threatening illness called paralytic shellfish poisoning in people who eat contaminated seafood. It is such a potent poison that the United States stockpiled it during the Cold War, and it’s now considered a chemical weapon under international law. It also has no known antidote—though something found in American bullfrogs might eventually change that.
A protein they make called saxiphilin can thwart the toxin in mice, researchers report in a study published in the journal Nature Communications on July 16. Scientists already suspected that the protein allows bullfrogs and other ribbiting amphibians to resist the effects of the harmful agent by binding to it, but the new work offers a path forward for potential therapies.
The protein acts like a “molecular sponge,” study co-author Daniel Minor, a biophysicist at the University of California, San Francisco, tells Lesley McClurg at KQED. “Basically, the saxiphilin is able to steal the toxin and filter it either to the liver or the kidneys to be excreted or removed.”
Around 2,000 people worldwide get sick from paralytic shellfish poisoning each year. Cooking or freezing seafood doesn’t kill saxitoxin, and affected shellfish look, smell and taste normal. But in just 30 minutes after consumption of contaminated food, symptoms like nausea, vomiting, numbness, high blood pressure and paralysis can set in, and death can occur just hours later. It’s fatal in about 8.5 percent of cases.
Quick fact: A century of investigation
Researchers first reported that frogs are resistant to saxitoxin in the 1930s. At the time, it was considered “muscle poison” because experts didn’t know it originated from algae.
To find a potential antidote, Minor and his colleagues conducted a series of experiments to see whether the bullfrog protein could protect mice given lethal doses of saxitoxin. As a control, 13 animals received injections of the toxin, and nearly all developed poisoning symptoms, like limb paralysis, within three minutes and died soon after. But providing the saxiliphilin before, during or after a toxic shot drastically changed the outcomes. Notably, giving just one jab with the protein one minute after poisoning allowed nine out of ten tested mice to avoid the toxin’s lethal effects.
Protein analysis of the mice’s carcasses helped the team determine where the bullfrog protein traveled in the animals’ bodies. The work revealed that levels were highest in the kidneys, followed by the heart and liver. Smaller but still significant amounts reached the brain and skeletal muscle, the latter of which could help explain its ability to protect against toxin-induced paralysis.
Saxitoxin blocks proteins called sodium ion channels located on the surfaces of cells. They’re important for nerve cell communication, which includes sending signals to make muscles contract.
“The saxiphilin is able to scoop up the toxin, keeping it from getting to the ion channels, and then transport it out so it can either be destroyed or excreted,” Minor tells Katarina Zimmer at Science News.
Rebecca Tarvin, an evolutionary biologist at the University of California, Berkeley who was not involved in the research, tells KQED that she was impressed the researchers looked at three ways the bullfrog protein could be used against saxitoxin: prevention before poisoning, neutralization with the toxin and rescue after exposure. “I thought that was sort of a comprehensive approach to assessing its potential for therapeutics.”
Still, many more studies are needed to make sure the treatment would safely work as a real-life treatment. “There’s a huge jump in taking something that works in mice and trying to develop it for humans,” Tarvin adds.
Further research should also ensure saxiphilin works against different types of paralytic shellfish toxins and evaluate the best delivery routes for the antidote, the authors write in the paper.
Minor hopes that this work inspires researchers to search for antidotes to other natural toxins. “Nature has had to solve this problem multiple times,” he says in a statement. “So, there is resilience to toxins all over the biological world.”
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