Antidotes from Ant Venom

  • Published25 Oct 2023
  • Author Ravindra Palavalli Nettimi
  • Source BrainFacts/SfN
Three red ants
Shutterstock.com via Creative Stock Studio

In June 2023, a Georgia woman died after stepping on a fire ant nest. Deaths due to ant stings are rare; roughly 1% of people are hyperallergic to ant venom. Still, ant stings can be agonizing. Justin Schmidt, an entomologist who created the insect sting pain index, ranked the fire ant sting at a pain level of one. The Amazonian bullet ant sting received the highest pain level of four. It is like “walking over flaming charcoal with a three-inch nail embedded in your heel,” Schmidt wrote in his book “The Sting of the Wild.”

From ouch to hospitalization, reactions to ant stings vary. But there is more to their venom than you feel. Scientists are uncovering how ant venom affects their victims, revealing unlikely insights that inspire antimicrobials, novel drugs, and a better understanding of pain.

A Concoction of Wide Varieties

Ant venom is a cocktail of chemicals. It includes formic acid, proteins (long chains of amino acids), peptides (smaller versions of proteins), alkaloids (organic compounds with nitrogen atoms), and allergens (which cause allergies).

Each component arises as adaptations over millions of years can provide ants with survival advantages. As ants evolved, various components contributed to their defenses against invaders and predators, their ability to hunt and subdue prey, and their chemical communication techniques such as alerting nestmates. Depending on the ant’s environment, the venom composition can vary from one to over 100 ingredients.

Ants in a container
With over 14,000 known ant species in the world, researchers can study a wide range of toxins across ant venoms.
iStock.com via Kaan Sezer

“There are over 14,000 [known] ant species in the world,” says Axel Touchard, a postdoctoral researcher at Cornell University. “The diversity of toxins is so amazing that I can continue to work on different ant venoms all my career.”

Venom from each species offers a different insight. That’s why Samuel Robinson, a molecular biologist at the University of Queensland, wants to identify the most unique components.

Ouch! A Neurotoxin

A single toxic component called poneratoxin is responsible for the bullet ant’s potent sting. This peptide acts on neurons and can cause excruciating pain. Robinson and his team grew sensory neurons from mice and added poneratoxin to find out how it affects them.

Bullet ant
This bullet ant, Paraponera clavata, owes its painful sting to poneratoxin — a neurotoxin in the ant’s venom that can fire off an organism’s pain signals for hours on end.
Shutterstock.com via Ryan M. Bolton

They discovered poneratoxin targets proteins called sodium ion channels, gated pores that allow sodium ions to flow into a neuron and fire it off. When poneratoxin binds to the gated pores on pain-perceiving neurons, it opens them, but prevents them from closing for an extended period, issuing a span of uncontrolled, prolonged pain signalling. Hence, the agony that feels like a bullet shot through the stung area.

“It’s a unique type of pain,” says Robinson. “If we can better understand sodium channels, we have a better chance of developing drugs targeting them,” which could lead to a “new class of painkillers.” Robinson’s group is currently working toward understanding how pain travels through the body and how to develop drugs to block the pain.

Ant Venom to Potential Products

Two U.S. patents, awarded in 1981 and 1993, asserted ant venom components can reduce pain in patients with rheumatoid arthritis. And in 1984, results from a study indicated ant venom could treat arthritis. But those venom components have yet to be successfully commercialized into a drug. Robinson says, “It shouldn’t be ruled out, but their efficacy hasn’t been proven.” Right now, no ant-venom-inspired commercial drug is on the market.

However, ant venom also holds promise for developing new antimicrobials and insecticides. Fire ant venom, which consists mainly of alkaloids called solenopsin, exhibits antimicrobial properties. Fire ants use them to protect themselves from microbes brought into their nest. They disinfect their nest by vigorously rubbing venom against nest surfaces, likely killing bacterial cells by creating pores and penetrating them. They even feed each other their venom, suggesting its use as an antimicrobial agent. An evolutionarily guided search strategy could help scientists identify these fast-acting and target-selective antimicrobials, which may also help combat issues like antimicrobial resistance.

Fire ants
Fire ant venom contains alkaloids called solenopsins. These chemical compounds exhibit antimicrobial properties, helping fire ants disinfect their nests.
Shutterstock.com via Young Swee Ming

Ant venom may also inspire new discoveries in peptide drug development. For example, researchers could isolate an inflammation-triggering ant venom peptide and re-engineer it into a drug to act as an anti-inflammatory agent by slightly changing the amino acid composition of the peptide. Other peptides from ant venom can paralyze or kill insects, which may spur a new generation of selective insecticides. To “develop new and effective bio-insecticides,” researchers like Touchard want to understand which molecules in ant venom act upon their insect prey.

In the end, the tiny ants scurrying past your picnic basket could hold a vast pharma toolbox for discovering novel drugs, insecticides, and more. 

CONTENT PROVIDED BY

BrainFacts/SfN

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