Researchers have discovered the venom of a notorious stinging caterpillar has a surprising ancestry and could be key to the delivery of lifesaving drugs
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Animal venoms are viewed as one of the best sources for new molecules with potential applications in medicine, agriculture, and science. But curiously, despite extensive studies of the venoms produced by snakes, lizards and spiders, next to nothing is known about the structure, chemistry, and mode of action of insect venoms, most of which remain completely uncharacterized to this day.
A team of scientists based at the University of Queensland sought to remedy this oversight. Inspired by their previous research into the venom of an Australian caterpillar, Doratifera vulnerans (ref), the team investigated the venoms of two species of asp caterpillars, Megalopyge opercularis and Megalopyge crispata.
There are 11 species of asp caterpillars, most of which resemble a fluffy cotton ball — or in some cases, a tiny version of Donald Trump’s toupee. They are native to North America where they are often found grazing on the leaves of oak or elm trees. But hidden within their fluff are sharp spines. These spines deliver a venom that sparks inflammation and excruciating pain that has been likened to blunt-force trauma or burning by the tip of a lit cigarette, a sensation that lasts for several days, at least. In some cases, the venom may provoke headache, nausea, and shock-like symptoms. Although a sting from one of these caterpillars won’t actually kill a person, it often requires a trip to the hospital, possibly because the pain it causes may make its victim wish to die.
Asp caterpillars are the larval form of flannel moths, which are small, extremely fluffy (and non venomous) moths. Of all the asp caterpillar species, perhaps the most notorious for stinging people is Megalopyge opercularis, the larval form of the southern flannel moth.
“Many caterpillars produce pain-inducing venoms and have evolved biological defenses such as irritative hairs, toxins that render them poisonous to eat, spots that mimic snake eyes or spines that inject liquid venoms,” venomologist Andrew Walker, who is lead author of the recent study and a Research Fellow with the Institute for Molecular Bioscience at the University of Queensland, said in a statement.
Liquid venoms themselves are comprised of biochemicals or proteins that sound like the poisons in an Agatha Christie novel.
“Many caterpillars have developed sophisticated defences against predators, including cyanide droplets and defensive glues that cause severe pain, and we’re interested to understand how they are all related.”
But unlike the Australian caterpillar, whose venom resembles those produced by spiders, wasps, bees and ants, Dr Walker and his team discovered that the two asp caterpillars’ venoms were distinct from venoms so far studied in any other insects.
“We were surprised to find asp caterpillar venom was completely different to anything we had seen before in insects,” Dr Walker said. “When we looked at it more closely, we saw proteins that were very similar to some of the bacterial toxins that make you sick.”
The toxins in the venom of asp caterpillars are very similar to toxins produced by disease-causing bacteria such as E. coli and Salmonella. These bacterial toxins act by binding to the surface of cells and assembling donut-like tunnels to create holes in cell membranes.
“It’s similar to the mechanism of box jellyfish venom — and as we’ve now found — caterpillar venom, too,” Dr Walker pointed out.
How did the ability to manufacture this venom get from bacteria into caterpillars?
“The venom in these caterpillars has evolved via the transfer of genes from bacteria more than 400 million years ago,” Dr Walker replied. This finding highlights the role of horizontal transfer in the evolution of animal venoms in general.
Apparently, the ancient ancestors of asp caterpillars remade these genes and their products into an efficient defensive weapon.
Further, the mode of action of asp caterpillar venoms gives them a lot of promise for medicine.
“Toxins that puncture holes in cells have particular potential in drug delivery because of their ability to enter cells,” Dr Walker explained. “There may be a way to engineer the molecule to target beneficial drugs to healthy cells, or to selectively kill cancer cells.”
Source:
Andrew A. Walker, Samuel D. Robinson, David J. Merritt, Fernanda C. Cardoso, Mohaddeseh Hedayati Goudarzi, Raine S. Mercedes, David A. Eagles, Paul Cooper, Christina N. Zdenek, Bryan G. Fry, Donald W. Hall, Irina Vetter, and Glenn F. King (2023). Horizontal gene transfer underlies the painful stings of asp caterpillars (Lepidoptera: Megalopygidae), Proceedings of the National Academy of Sciences, 120(29):e2305871120 | doi:10.1073/pnas.2305871120
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