The most abundant animals on farms—and everywhere on land, in fact—are microscopic worms called nematodes. Some kinds benefit the soil, but others parasitize crops, inflicting more than $100 billion in losses worldwide each year. Although pesticides can get rid of harmful nematodes, they inflict collateral damage on other life.
Now, researchers have discovered a new chemical that selectively kills harmful nematodes with a much lower risk of toxicity to humans and other creatures. “This is really unique,” says parasitologist Tim Geary of McGill University and Queen’s University Belfast, who was not involved. “It could offer a way to improve control of crop pests.”
Farmers try to prevent nematode damage in various ways. Rotating crops, sterilizing soil with plastic sheets, and planting nematode-resistant crop varieties can all help control the problem, but the most effective solution is treating fields with pesticides. Yet most of the widely used chemicals known to kill nematodes have been banned because of their toxicity to humans and wildlife. In 2004, chemical manufacturers began to phase out methyl bromide, another chemical widely used to fumigate soils, because it harms Earth’s ozone layer. Since then, chemical companies have developed several new, safer pesticides for nematodes.
The latest candidate comes from the lab of Peter Roy, a chemical geneticist at the University of Toronto (U of T). In recent years, he and colleagues have evaluated about 100,000 small molecules to see whether they kill Caenorhabditis elegans, a harmless nematode whose biology is well known to scientists. If the lab identifies a chemical lethal to C. elegans, Andrew Burns, a biochemical geneticist at U of T, and colleagues check whether it also harms other kinds of organisms, such as fungi, insects, and mice. “We’re not interested in chemicals that are going to kill everything,” he says.
In 2016, a compound that passed those tests caught Burns’s interest. Its chemical structure resembled a drug called levamisole, which is used to treat livestock infected with parasitic nematodes, but the compound had different effects on the worms. Levamisole paralyzes them, whereas the newly discovered small molecule—dubbed selectivin—kills them outright.
Further experiments revealed selectivin’s lethal methods. Once the nematode’s body absorbs it, the worm modifies it with enzymes, called cytochrome P450s, which in many organisms detoxify foreign molecules. But for some reason, the nematode version of cytochrome P450 instead turns selectivin into a toxic chemical. “That was the first aha moment for me,” Burns says. Cytochrome P450 needs oxygen to function, so Burns hypothesized that selectivins might be good for killing nematodes that live in soil, where oxygen is abundant.
This “bioactivation” of the chemicals didn’t happen in other kinds of organisms tested, perhaps because their versions of cytochrome P450 deal with it safely, which suggests it would be nontoxic to humans, wildlife, and soil microorganisms. A structurally similar molecule even leaves some beneficial nematodes unharmed, such as Phasmarhabditis hermaphrodita, which kills slugs and snails that would otherwise eat crops. Some farmers also release certain kinds of beneficial nematodes to control insect pests, which the worms infect and kill.
A new pesticide that leaves these beneficial nematodes unscathed while killing the plant-parasitizing nematodes would be a boon, says Charles Opperman, a nematologist at North Carolina State University. “It would really provide more options for growers to maintain soil health.”
Next, the team collaborated with researchers at the U.S. Department of Agriculture to try selectivin against a notorious and nefarious nematode, Meloidogyne incognita, which infects many kinds of crops. In tests with greenhouse tomato plants, selectivin controlled the nematodes as well or slightly better than existing pesticides, the researchers report in Nature.
Another advantage of selectivin is that it may be cheaper to manufacture than existing pesticides used against nematodes. Only two cheap solvents are required, and the needed chemical reactions could be completed without expensive catalysts or high temperatures. “The fact that it’s relatively inexpensive to manufacture could be a big deal,” Opperman says.
There’s still a long way to go before the new chemical is available to farmers—most pesticides require 10 years of experimentation and $250 million or more to ensure efficacy and safety before reaching market. The challenge hasn’t deterred Roy, however, who is eager to find commercial partners to help move the drug through development.
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May 26, 2023 at 05:04AM
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Newly discovered chemical is a highly targeted killer of parasitic worms - Science
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