Face off: Bull ant goes head-to-head with echidna in evolutionary battle

By Karen McGhee 21 April 2022
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Queensland scientists have identified a toxin in bull ant venom that seems to have cleverly evolved specifically to target short-beaked echidnas, the main predator of ants in the Aussie bush.

But there’s even better news. This breakthrough could help in the treatment of human pain.

The discovery that Australian bull ants and echidnas share an entwined evolutionary history began about four years ago when Dr Sam Robinson, a molecular biologist and expert in animal toxins at The University of Queensland, was handed a container of these stinging insects.

There are 93 species in the group we know as bull ants – the genus Myrmecia – and all but one of them is endemic to Australia and its islands. The short-beaked echidna also is a peculiarly Australian animal, found nowhere else in the world.

Sam’s research now indicates that these two have been engaged in a long-term evolutionary battle of survival in which the ants have deployed pain to stop echidnas from plundering their nests.

Australian bull ant emerging from its nest. Image credit: Dr Sam Robinson

Seriously nasty stingers

Bull ants is just one of the common names for these ants: they’re also known as bulldog ants, jack jumpers and inch ants. “They are all large ants and probably the most characteristic thing about them is their large mandibles,” Sam explains.

“Another thing about them is that while a lot of ants will use ‘smell’ [chemical trails] to get around, these ants are very visual.”

Watch them for a while and you might notice them sending semaphore-like messages to each other by waving their antennae.

“And the other thing we know is that they sting, and it hurts,” Sam adds.

Get bitten by one of these things and you’ll know it!

It’s the venom that stings and that’s what Sam set out to explore when he was first handed that container of ants.

“Generally, at that time, we knew very little about what was in ant venoms,” Sam says. “And I thought this was a really cool place to start, with one of these really charismatic Australian ants.”

Dr Sam Robinson.

Obsessed with pain

By then Sam had already been studying venoms for several years.

“I’d already looked at a whole bunch of different ones by then,” Sam explains. “But my broader research program is looking at trying to isolate things that cause pain and the particular toxins in venom that cause pain.

“I want to understand how those work on the human body and use that information to almost rewrite the book on pain at a molecular level.”

The reason for doing that is that if you can understand how pain – which is an extremely complex physical response in the human body caused by a staggering array of triggers – then you’re in a better position to be able to develop ways of alleviating it.

Researchers in Australia have been successfully extracting and collecting venom from snakes and spiders for decades. But those techniques don’t work on ants. To investigate what is in ant venom, Sam had to first develop a way to safely collect it.

“And that has been to basically just get them to sting at a little waxy paper strip and then collect the droplets off that,” he says. “Then we figured out what was in that venom by using some fairly complicated techniques.”

Australian bull any nest. Image credit: Dr Sam Robinson


Sam’s team then published a paper that for the first time characterised an ant venom – essentially breaking down its chemistry.

It allowed a complete picture of what’s in the venom, which made it possible to determine the structure of every molecule it contains.

“This let us see how it was working,” Sam says, explaining that most of the molecules turned out to be related to and work in a way that’s similar to the main toxin in honey-bee venom – melittin.

These toxins punch little holes in cells and when they do that in a nerve cell – a neuron – it activates it. “It’s a pretty common mechanism of action for pain-causing toxins,” Sam says. “But there was one stand-out that was structurally very different to the rest of these toxins.”

Sam’s team tested that toxin in laboratory mice but couldn’t get a pain response from it.

In fact, they couldn’t get any sort of response to it, so it was set aside and kind of forgotten for a while until Sam was stuck in COVID quarantine and decided to take a much closer look at that aberrant molecule.

Short-beaked echidna. Image credit: Shutterstock

Identifying a connection

After running the molecule against a massive database of other molecular structures something unusual appeared.

Sam was looking for molecules with a similar structure and “one thing that jumped out at me was that the things at the top of the list were actually these hormones from Australian marsupials”.

Surely, he thought, this can’t simply be a coincidence. “There’s this ant that’s endemic to Australia and we’re getting a strong signal for Australian animals,” Sam says.

He then looked into the scientific literature – beyond his usual molecular focus and into more ecological areas – and realised that the thing likely to be applying the strongest selection (evolutionary) pressure on these ants was the echidna.

“It’s the only Australian animal known to actually dig up ant colonies – to eat their larvae and eggs – and I thought if that’s the animal that’s attacking them perhaps this toxin is mimicking a hormone in the echidna for some reason related to pain,” Sam says.

“So, I looked at the echidna genome, which was only published a couple of years ago, and sure enough found this hormone sequence in there and it was the most closely related thing to this toxin that we’d seen.

“It was pretty strong evidence that there was this link between bull ants and the echidna and that the toxin had evolved to target a receptor in the echidna.”

Previous studies had suggested that this particular receptor might be involved in pain hypersensitivity. The team then repeated its laboratory experiments, this time not simply injecting the bull ant toxin into mice but following that up by applying pressure to the area that was injected.

“We simply took a little wire and pressed it against the mouse foot and just measured when it started to recoil from that,” Sam explains.  “It wasn’t painful; just a measure of sensitivity.

“And what we found was that the mice had become extremely sensitive within a couple of hours to any mechanical or thermal stimulus.”

The researchers kept measuring and found that this heightened sensitivity lasted for about a week.

“So, what we think is going on is if an echidna is to say attack a bull ant colony, it’s going to get stung by a lot of ants as anyone that goes and meddles with a bull ant colony will, and it’s going to get a big dose of this toxin,” Sam says.

“Then if it returns to that colony later to raid it again, or to a neighbouring colony, it’s probably going to avoid that because it’s going to be a whole lot more sensitive to the pain of the experience.

“So, it probably reduces the duration an echidna can stay at a bull ant colony or the frequency at which it is going to target bull ant colonies.”

Not surprisingly studies of echidna foraging show that they tend to eat other ants, not those in the bull ant genus.

“These ants make up a small percentage of what echidnas eat – maybe only 5 or 10 per cent,” Sam says. “They’ll target things that are a lot easier.”

Perhaps this shows that the ants’ strategy has worked? “We don’t yet have any direct evidence for that, but you would assume it to be the case. I mean if you were an ant eater and had a choice of two different ant colonies and one of them hurt a lot more you’d probably avoid that one!” 

To Sam the most remarkable aspect of this work so far has been to see how closely the structure of ant toxin so closely mimics the hormone in echidnas. “It’s quite amazing,” he says.

And clearly, he agrees, it’s a beautiful example of evolution in action.

Help for human pain

There’s so much more to this discovery, however, than the exquisite light it throws on understanding the natural history of Australian animals.

There’s the potential it might hold in the long-term for the treatment of some forms of pain.

Pain is a complex phenomenon that manifests itself in many different ways:  one is chronic hypersensitivity, and this is seen in certain diseases such as particular types of migraines and some cancer-related pain.

“Really the key thing in the context of pain is that, by highlighting a receptor involved in pain hypersensitivity, the bull ants have revealed a potential new drug target,” Sam says. And that, he agrees, is really one if the major goals of his research.