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Science Insider

A New Miticide?

- December 1, 2022 - Alison McAfee - (excerpt)

As concerns over miticide resistance grow, Canadian researchers are developing a new product

Rumors have been simmering for a few years already, and now, the hard evidence is mounting. As Erika Plettner, a chemistry professor at Simon Fraser University, said to an audience of beekeepers at the BC Honey Producers’ Association annual meeting, “The question was not if, but when and how resistance would develop.”

Mites are becoming resistant to amitraz, the active ingredient in Apivar. Frank Rinkevich, a researcher at the USDA Agricultural Research Center in Baton Rouge, Louisiana, formally documented this in a study released in 2020.1 He showed that Apivar was still highly effective in most commercial beekeeping operations, but in others, efficacy had waned to 70%, when it should be closer to 100.

These trends are worrying, but not as worrying as what I’ve seen in our research colonies. In early fall, we found that some of our colonies had a 10-fold increase in mites during an Apivar treatment, spurring us to do an emergency formic acid application, made possible by an unseasonably warm October. And this alarming loss of efficacy is despite rotating between three different miticides — amitraz, formic acid, and oxalic acid — every year.

More recently, Rinkevich reports seeing amitraz resistance in one third of the operations he surveys. He says this is likely an over-estimate, but still, something needs to change. “New miticides, especially those with new modes of action, are valuable tools to control varroa,” he says, but cautions against a rapid shift in use and overreliance, should a new acaricide come on the market.

Plettner and other researchers at SFU, Beaverlodge Research Station, and the University of Alberta are working on just that — a new miticidal compound, which Plettner calls 3c{3,6} (known formally as 1-allyloxy-4-propoxybenzene) — generating much excitement among beekeepers. It both kills and confuses varroa, making it stand out against other synthetic miticides. But, Plettner warns, “as long as there is life, there will be evolution,” and resistance is just evolution on speed.

“There is no miticide in shining armor that will solve our varroa problems,” Rinkevich echoes.

That said, beekeepers are on their heels. Some have been taken by surprise by the growing amitraz resistance, which has, until now, been slow to develop. Apivar was formally registered across the U.S. in 2013 (2012 in Canada), but it was used in many states well before that. Despite at least two decades of use in North America, serious amitraz resistance has shown up only recently, and no new synthetic acaricides have come on the market since.

Plettner and her colleagues did not set out to find a new miticide for beekeepers: They unearthed 3c{3,6} by chance, but it’s now one of the most promising new miticides on the docket — possibly the only one. The researchers first identified this compound as a feeding deterrent for cabbage looper (Trichoplusia ni) larvae, a common crop pest, in a screen involving an array of chemicals, where 3c{3,6} emerged as the most effective.

“Since it is so good at deterring feeding of T. ni larvae,” Plettner says, “my thought was to look for activity with other problematic arthropods, including varroa. That’s when we noticed the acute activity — paralysis and death.” In 2019, the team filed a patent for using this compound as a varroa treatment, which is pending, and a therapy using this compound is in the early stages of research and development.

Plettner and colleagues first experimented with this compound in the lab, where they found that 3c{3,6} not only kills and paralyzes mites, it also seems to disrupt their sense of smell.2 Varroa mites need to be able to first sense, then latch onto their host in order to disperse within the nest and between colonies, so disrupting their sense of smell could transform them into scatterbrains, possibly extending their hitchhiking phase and giving bees a better chance to groom.

In a paper co-authored with collaborators in Rishon LeZion, Israel, the researchers used a technique called electrophysiology to measure nerve impulses in the forelegs of varroa and antennae of honey bees that had either been exposed to 3c{3,6} or not. Mites use their forelegs to smell things in their environment, like how bees use their antennae. The scientists could then puff an odorant, like the smell of a nurse bee, over the mite and measure how strongly the foreleg nerves fire, which is an indication of their ability to smell what’s in the puff of air.

The researchers found that exposing mites to 3c{3,6} flattened their ability to sense the odor of nurse bees by about two thirds, whereas honey bees’ sense of smell was apparently unaffected. In work that is not yet published, Plettner has also found that, in laboratory tests, 3c{3,6} has miticidal and paralysis activity comparable to thymol, the active ingredient in Apivar and Thymovar, and is well-tolerated by honey bees. Together, these results imply that, in a beehive, 3c{3,6} might act like a 1-2 punch, first confusing, then killing the mites.

Now, Plettner and her team have moved into field trials. Over the last three years, they have refined their hive application methods and are currently counting thousands of mites on sticky boards from this year’s experiments. Once in, these data will let them calculate the efficacy rate (percent mite kill), which will provide the best indication yet of whether this will be a viable treatment option for the industry.

3c{3,6} might have some advantages over existing treatments, but it also presents some unique challenges. Because the compound is relatively non-volatile, Plettner expects that should facilitate a wider treatment window, in terms of ambient temperatures, compared to thymol- and formic acid-based products. But its chemical properties also mean that it’s likely to be absorbed into wax and not reach varroa within capped cells. It is not yet known if buildup in wax will be a problem for bee health, as sublethal effects are yet to be investigated.

More practically, unlike other acaricides, 3c{3,6} is not already registered for other agricultural or veterinary uses, so safety assessments for use in beehives cannot piggyback on a history of safe use elsewhere.

In fact, the chemical is so new that the researchers had to first demonstrate that it was safe for humans to work with before even getting to the bees. It’s not available from chemical supply companies, and must be synthesized in the lab by chemists with specialized knowledge. All this is will probably slow down efforts to develop the project, and Plettner expects that registration and scaling up production of the compound will be their biggest hurdles.

But the novelty of this compound might not be such a bad thing. For miticide rotations to be effective, the miticides being rotated should work via different mechanisms of action. The mechanism of 3c{3,6} is not yet known, but, given that its chemical structure is different from all other synthetic miticides (though it has some similarities to thymol), the mode of action is likely different, too.

Although having a new miticide will only allow beekeepers to get ahead of varroa temporarily, at the very least, having a wider selection of products to rotate through will help slow the development of resistance to each one, as part of what Rinkevich calls “product stewardship.”

“We need to think of miticides as a tool for varroa management, not a silver bullet,” he says, adding that we need to adopt multiple techniques for managing varroa, including cold storage for consistent brood breaks, improved genetics, and others, as part of a “redundant varroa management system.” Plettner, too, advocates for other   ….