Stonefish toxin could be new weapon against one of livestock's biggest threats

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Squeezed from the skin of a stonefish, a recently discovered toxin shows enormous promise, according to researchers in Far North Queensland.

Squeezed from a "pimple-like" tubercle on the skin of a stonefish, a recently discovered toxin has enormous promise, according to researchers in Far North Queensland. The compounds have been shown to kill helminths or parasitic gastrointestinal worms while leaving mammal cells unharmed, said Danica Lennox-Bulow, a PhD candidate at James Cook University. The team's research was recently published in the journal Toxins.

Ms Lennox-Bulow said the toxin was different from the one stonefish were usually known for, which comes from the fish's venom glands in its spines. "This toxin is completely different from the venom in both its composition and its function, and it's secreted from these wart-like nodules that span the animal skin," she said. Ms Lennox-Bulow said the idea to investigate stonefish skin toxins came after earlier research discovered the animals had a surprisingly low amount of internal parasitic worms.



The fish spend most of their lives sitting on the ocean floor — often partially buried in sediment and with algae growing on them — to hide from predators but also to aid their ambush-predation. Danica Lennox-Bulow has been researching stonefish at James Cook University for several years. This lifestyle, combined with their scaleless skin, meant the lack of parasites, which typically burrowed through the skin, was very surprising, according to Ms Lennox-Bulow.

"That raises a huge question, the question of whether they could be using this skin toxin to protect them," she said. The research After extracting the skin toxin from both reef stonefish ( ) and estuarine stonefish ( ), Ms Lennox-Bulow and other researchers first applied it to a skin-burrowing hookworm larvae that typically infects rodents. "We found, after putting this toxin on to this parasite, that we got a high mortality rate," she said.

The next stage involved separating the toxins into small and large components, using a centrifuge and re-testing them on the hookworms. When separated, the toxin from the reef stonefish lost all toxicity, which "suggests to us that it might be a synergistic effect between the components," according to Ms Lennox-Bulow. Researchers separated the components of the toxin using a centrifuge and retested their toxicity.

However, with the estuarine stonefish, the smaller components remained toxic. "From a therapeutic perspective, small components are extremely favoured because they're often very stable, they're easy and cheap to manufacture in the laboratory, and they're also typically bio available, so they can be taken as a sort of a pill," she said. The final stage involved testing the components on human and other mammal cells, which found little to no effect on those cells — a positive sign according to the researchers if the components were to be considered in therapeutic spaces.

Ms Lennox-Bulow said they hoped to expand the research in future to see if it would remain toxic to worms and harmless to mammals in other animals. An arms race Anne Beasley from the school of Agriculture at the University of Queensland said intestinal parasites were a massive problem for Australian livestock producers and any new research in this area was welcome. Infestations most commonly affected sheep, goats and cattle, Dr Beasley said, and some estimates for the cost to the sheep industry alone are more than $600 million per year.

She said helminths could cause issues including reduced weight gain, poor wool production, lower milk yields among other health issues — even death. Sheep are some of the livestock in Australia worst affected by parasitic worms. (file photo) "They suck blood, or they damage the lining of the intestine, and so animals can end up really, really sick in a short period of time.

" 'Critical' need for alternative treatments Dr Beasley said the breeding capacity and life-cycle of some worm species meant their resistance to treatments could build quickly. "Some of them can produce up to 5,000–10,000 eggs per female per day," she said. Stonefish secrete a different toxin in the bumps on their skin known as tubercles.

"We've been relying on the same drug classes for quite a long time now, and so the worms have simply evolved to survive those ones." Dr Beasley said the need for new options was "critical". "We need our researchers to be really creative and innovative in their search for new approaches to parasite control, and that includes things like screening new and novel compounds, like this research is doing from Cairns.

" Stonefish lack scales, which researchers say makes them vulnerable to parasitic worms. But, Dr Beasley said it could take many years and millions of dollars for new compounds to reach the commercial market. "There are significant production losses and deaths that are occurring right now because of parasite issues, so the more people we can have working on this issue, and the more attention we can put on it, I think the better.

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