A multidisciplinary group from the Queensland University of Technology (QUT) has identified 84 toxins produced by Australian sea anemone Telmatactis stephensoni that exhibit biological properties of potential interest for human therapeutics.
In a recent issue of the journal Molecular Ecology, QUT PhD researcher Lauren Ashwood and colleagues report their findings, including the discovery that the toxins display distinct biological functions and were located at sites that corresponded to their function.
“Unlike snakes which deliver their venom via fangs, T. stephensoni venom is a complex cocktail of toxins that is found in stinging cells throughout the sea anemone’s structure,” Ashwood said. “Analysis of the sea anemone’s three major functional regions: the tentacles, epidermis and gastrodermis—found the locations of toxin production are consistent with their ecological role of catching prey, defense and digestion. This means when we study the toxins in the context of what they do, we have an idea of how they might be useful for therapeutics.”
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Animal venoms have long been used to treat humans throughout history, with snake venom administered medicinally as early as the seventh century BC. Peptide toxins from venomous animals are being developed into therapeutics for conditions, including cardiovascular disorders, autoimmune diseases, diabetes, wound healing, HIV, cancer and chronic pain.
“In all we found 84 potential toxins in T. stephensoni including one that hadn’t been seen before. A sample of this unknown toxin, named U-Tstx-1, has been sent to a specialized lab in Hungary for analysis,” Ashwood says. “Given that this toxin was found in the gastrodermis of the sea anemone it could be involved in digestion[, and] it could be a new type of co-lipase, enzymes that break down fat. This toxin could also be similar to a toxin in the venom of black mamba snakes that stimulates intestinal muscle contractions.”
Co-researcher QUT Associate Professor Peter Prentis, from the Centre for Agriculture and the Bioeconomy and the School of Biology and Environmental Science, said there is research interest in pain-causing venoms because they could potentially be developed to provide pain relief.
“If we can isolate the neurotoxin and find the nerve cell receptor it activates, we could potentially develop a blocker to stop activation and treat conditions such as chronic back pain,” Professor Prentis said. “This means the toxins in the acontia—long, stinging thread used to ward off would-be predators that cause intense pain to marine animals as well as humans—could be a source of an ‘antidote’ to some types of chronic pain.”
New analytical techniques have led to a shift towards toxin-driven discovery and away from earlier methods where crude venom was first tested against a target for desired activity. “This new strategy allows for the discovery of peptides that might have remained undiscovered, for example, those which may not be highly abundant in the venom or which possess unanticipated mechanisms of action,” Prentis says. “Toxin-driven discovery to find therapeutic candidates, however, can be like finding a needle in a haystack and not all peptide toxins are likely to have the same success as pharmaceuticals.”