Finding new uses for nature’s poisons

A toxin is a poisonous substance produced by a living thing. Certain species of plants, fungi and animals may produce toxins. So can bacteria. (When a toxin is injected, through a bite, sting or other means, it is called venom.) Poison dart frogs absorb toxins from the ants, millipedes, beetles and mites that they eat. The frogs then secrete those toxins from their skin. That protects them from getting eaten. Some of these rainforest frogs are so toxic that just touching them can bring death.

Other organisms have evolved different types of poisons. Many of these chemicals attack microbes, fungi, insects and other threats in ways that make it unlikely they will become resistant to the poisons.

Scientists are finding ways to adapt compounds that frogs and other animals rely on for protection against threats in their environment. These compounds can be put to use fighting pests that threaten human health, the environment and the food supply. Frog poisons, for instance, can be used to fight insects such as the mosquito. Already, some of these natural compounds are being enlisted to guard human health and safety.

Throughout nature, one organism’s defense can become another’s offense — and vice versa. Here we meet some scientists who look at poisons not as a source of fear but as a raw material for drugs and other useful chemicals. They’re investigating how to harness toxins — Mother Nature’s chemical weapons — for the good of people and the environment.

Turning microbes into Swiss cheese

For decades, people have used drugs called antibiotics to kill bacteria that cause disease. Many bacteria, though, have become resistant to antibiotics. As a result, these infections are becoming much more difficult to treat. But natural compounds, including toxins, are providing a new way to fight these microbes.

Michael Zasloff discovered one of these beneficial toxins by accident. It was the late 1980s, and Zasloff was a medical scientist at the National Institutes of Health (NIH) in Bethesda, Md. (He now works at Georgetown University in Washington, D.C.) At NIH, he used ovaries from African clawed frogs for genetic studies. After surgery to remove the ovaries, he placed the frogs in a tank to recover. One day it dawned on him: Almost all of the frogs healed without infection. And it happened even though their water teemed with germs.

African clawed frog
The skin of these African clawed frogs contains germ-killing chemicals that help them heal, even when their water is not sterile. MUFFET/WIKIMEDIA COMMONS (CC-BY 2.0)

Zasloff examined the frogs closely. He discovered their skin contained a group of compounds that attacked bacteria. He named them magainins (Muh-GAYN-inz). The name comes from the Hebrew word for shield.

Peptides are short strings of amino acids that are similar to (but usually far smaller than) proteins. Magainins turned out to be one class of peptides withantimicrobial — germ-killing — properties. All types of life produce these peptides. They form one of the most basic defenses against pathogens, or disease-causing microbes.

Antimicrobial peptides kill bacteria by poking holes in their cell membrane. This is the soft outer wall surrounding each cell. These holes break down the bacterial cell’s ability to function. Even better: Antimicrobial peptides can also attack protozoa, fungi and viruses.

But with bacteria, the peptides attack in a way that is very different from antibiotic drugs. “Conventional antibiotics are like keys in a lock,” explains Zasloff. The antibiotics fit into specific proteins — or locks — and block their function. Depending on the antibiotic, those target proteins can be located inside a germ or on its surface. But all it takes is a slight change in the shape of that protein “lock” for the “key” to stop working, he says. That’s what makes it so easy for bacteria to evolve resistance to antibiotics.

In contrast, magainins burrow through a microbe’s cell membrane. The peptides effectively turn that membrane into Swiss cheese. To evolve resistance, a microbe would have to alter the structure of its membrane. That type of change would be too difficult for the microbe to easily make, says Zasloff.

Promising as it is, this new class of antibiotics is not yet ready for use in people. That’s because some of these compounds can be very costly and too toxic.

Still, the power of antimicrobial peptides already benefits many people. Consider nisin (NY-sin). Bacteria called Lactococcus lactis (LAK-tow-KOK-uss LAK-tiss) make it. This toxin is not harmful to people. Indeed, some manufacturers use it to make buttermilk and cheese. The bacteria make nisin as a poisonous defense against other bacteria, including those that cause two potentially deadly foodborne illnesses in people: botulism and listeria.

Today, scientists grow large batches of L. lactis. Then they extract nisin, which food companies often add to foods (such as processed cheese) and to food packaging. Listed on labels as E234, nisin keeps potentially deadly germs from growing on foods.

Fighting pests with frogs and mites

Antimicrobial peptides have been found in a wide variety of organisms, including people. They act as the first line of defense against invading microbes. That’s why these natural germ killers are common on the skin. More than 300 of these peptides have been found on frog skins alone.

The skin of some frogs also contains compounds called alkaloids (AL-kuh-loidz). These are the poisons in poison dart frogs. Those alkaloids can protect a frog from predators and kill germs.

ant in tube full screen
A fire ant is trapped in a glass tube by a plunger coated with poison dart frog alkaloid. BOB VANDER MEER/USDA

A fire ant is trapped in a glass tube by a plunger coated with poison dart frog alkaloid.

BOB VANDER MEER/USDA

You can’t see the toxic alkaloids on a frog’s skin. Fortunately, a frog usually advertises — with a colorful skin sporting bold patterns — when those poisons are present. That coloring makes them easy to spot and avoid.

In fact, many animals that bear such colorful warnings are toxic in some way. For some, it can be a venomous bite or sting. For others, it’s enough to taste bad if eaten. Maybe you have seen a dog pick up a toad in its mouth and spit it out again. If so, you’ve probably seen alkaloids in action. Along with frogs and toads, other animals that use bright colors to advertise their toxicity include wasps, butterflies and even some birds.

The deadly alkaloids lurking on the skin of poison dart frogs keep them safe. At just 2.5 centimeters (about 1 inch) in length, the frogs would make a perfect snack for many birds, fish or mammals. But forget taking a taste. Even touching one of these frogs can prove deadly. Scientists have identified some 900 alkaloids in the skin of poison dart frogs.

Robert Vander Meer wanted to learn whether these alkaloids might also protect the frogs from insect predators. As a chemical ecologist with the U.S. Department of Agriculture (USDA) in Gainesville, Fla., Vander Meer studies the role of chemicals in plants, animals and their environment. He focuses on red imported fire ants.

The species first entered the United States in the 1930s. It likely stowed away on ships headed for the southern United States from Argentina. Today, this ant is one of the world’s worst invasive species. (Lacking natural predators in its new home, an invasive species tends to spread rapidly, often harming its ecosystem.) Red imported fire ants are aggressive. People who live where these ants are found face a 1-in-3 chance every year of being stung, says Vander Meer. And their stings don’t just hurt. The ant’s venom actually kills insects, turtles, snakes — even young birds. Finding ways to control the ants is one of Vander Meer’s goals.

twisted ant
A fire ant experiences convulsions following exposure to poison dart frog alkaloids. The alkaloid this ant was exposed to originally came from mites. BOB VANDER MEER/USDA

For a recent study, he selected 20 alkaloids from poison dart frogs. One species lives in areas of Central America that also are home to fire ants. The alkaloids had been isolated earlier by other scientists. This allowed Vander Meer to select only the ones he desired.

Vander Meer and his colleagues then brought local fire ants into the lab. There they used a bioassay to determine whether any of the alkaloids affected the ants. A bioassay looks for the effect of compounds, such as toxins, vitamins or hormones, on animals. (If you have ever had an allergy test, you have taken part in a bioassay.)

Here is how that test worked. First, the experts removed the plunger from a syringe (like the one used to spritz flu vaccine into your nose) and coated its end with one of the alkaloids. When the plunger was dry, the researchers placed a single ant inside a glass tube that had been sealed at one end. Then they inserted the plunger into the tube until it touched the ant’s body (usually its abdomen). The plunger fit snuggly against the walls of the tube,. That prevented the ant’s escape.

After three minutes of contact, the ant was released into a Petri dish. There, the experts centered the ant on a piece of paper marked like a target. The circles on the target were 2 centimeters (0.8 inch) apart. This allowed the researchers to measure how far the ant could move in a short period. The team also repeated the test using untreated plungers. This means that some of the tests didn’t expose the ants to any of the alkaloids. That helped scientists learn whether it was an alkaloid, and not the cramped conditions, that caused a specific response.

Not all alkaloids affected the ants. For instance, toxins that the frogs originally obtained by eating fire ants had no effect. And that makes sense, explains Vander Meer. After all, fire ants have to be resistant to their own poisons. But some other alkaloids reduced the ability of the ants to walk for a time. Still others provoked convulsions and ultimately killed the insects. Those alkaloids had come from frogs that had dined on small relatives of spiders, known as mites. Now that the scientists know the source of those compounds, future studies may not require them to use frogs. They can go straight to the mites.

The alkaloids won’t be useful in the fight against red imported fire ants, notes Vander Meer. The reason: They act too quickly. Effective control requires slow-acting poisons. Such poisons, whether natural or not, can be mixed in with ant food. Foraging ants then take the bait back to their nest. There, they will share the toxic meal with thousands of unseen workers. In time, the whole colony can die.

But the alkaloids could play an important role against another pest — mosquitoes — and the tropical diseases that they carry, notes Vander Meer. Some of these blood-sucking insects carry yellow fever, chikungunya, malaria and other diseases. Fabric sheets treated with alkaloids could be hung on the walls of homes to kill mosquitoes and protect against devastating diseases.

The trick, Vander Meer points out, is to modify the alkaloids. He and others are working to do that. Without changes, the alkaloids not only are toxic to mosquitoes but also to people. Even slight changes, though, might greatly alter how alkaloids work, he notes. And that may permit scientists to develop a version safe for people but still deadly to insect pests.

BY
7:15AM, OCTOBER 9, 2015
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Source: Cool Jobs: Finding new uses for nature’s poisons | Science News for Students

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