Varroa and the honeybee: Researchers help fight a modern parasite battle

Published in Social Sciences and Microbiology

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BioMed Central
BioMed Central BioMed Central

RNAi targeting ABCB1-like efflux transporters improves miticide efficacy in resistant Varroa mites

Background The ectoparasitic mite Varroa destructor is the gravest threat to managed honeybees, and its control relies on a limited number of chemical miticides. Among these, amitraz is widely used because of its strong efficacy against mites and relatively low toxicity to bees. However, increasing resistance to amitraz in Varroa populations threatens its long-term effectiveness. While mutations in the mite’s β2 octopamine receptor are strongly associated with amitraz resistance, additional mechanisms influencing toxicant uptake and efflux are believed to also contribute. ATP-binding cassette (ABC) transporters, including ABCB1/P-glycoproteins, are well-established mediators of xenobiotic efflux and pesticide tolerance across arthropods, making them promising targets for silencing via RNA interference (RNAi) to combat miticide resistance. Methods We cloned a full-length Varroa ABCB1-like transporter (VdABCB1) and synthesized dsRNAs targeting its coding sequence. Adult mites were treated with dsRNA prior to amitraz exposure in laboratory bioassays. Mite survival was analyzed longitudinally, and resistance-associated β2 octopamine receptor genotypes were determined. Varroa transcriptomic responses to dsRNA were assessed by RNA sequencing. Honeybee safety was evaluated in cage assays following chronic oral dsRNA exposure, including conservative tests co-administered with a known ABC transporter substrate. Results Mites exposed to ABCB1 dsRNA showed greater amitraz-induced mortality than those treated with non-specific dsRNA. This effect was observed across multiple trials and amitraz concentrations. Transcriptomic analyses of mites revealed a significant knockdown of ABCB1-like transcripts following RNAi treatment. Chronic dietary exposure to ABCB1 dsRNA did not impact honeybee survival. Toxicity assays with ABCB1 dsRNA on its own or together with acetamiprid (ABC transporter substrate) as a high-risk interaction control showed minimal adverse effects on bees. Conclusions RNAi suppression of Varroa ABCB1-like transporters increased amitraz mortality in resistant mites, identifying transporter-mediated efflux as a modifiable component of amitraz resistance. These findings demonstrate that targeted disruption of detoxification pathways can enhance miticide efficacy while minimizing off-target effects in bees. RNAi-based synergists therefore represent a selective resistance management strategy that could extend the effective lifespan of amitraz and other miticides relied on by the beekeeping industry. Graphical abstract

The world has seen a significant decline in honeybee populations in the last several decades. The greatest threat to honeybee populations is the parasite, Varroa destructor. Varroa destructor is a tiny, crab-shaped mite about 1 mm in size that generally poses no threat to humans or animals. But for Western honeybees (Apis mellifera), the most common honeybee species in the world, it lives up to its villainous name.

Close-up of honeybee pollinating on purple flower. Jonas Olbrich / 500 pix via Getty Images.
Close-up of bee pollinating on purple flower. Jonas Olbrich / 500 pix via Getty Images.

Varroa nests with honeybee larva in its brood cell, where it feeds on growing honeybee fat bodies, and infects the bee larvae with deadly viruses. Varroa has been determined responsible for a recent mass honeybee die-off event, where over 60% of US beekeepers’ colonies, in 2024-2025. This was the second mass die-off event since the turn of the millennium, with the first one in 2006-2007, which had multiple causes.

For these reasons, Varroa destructor has become the bane of beekeepers since it was first introduced to Western honeybee populations in the mid 20th century. The principal strategy to fight Varroa infestations is through chemical pesticides that target arthropods, also known as acaricides, or miticides. Principal among these is amitraz, which like other acaricides, is a potent neurotoxin that causes paralysis and death in Varroa.

Varroa destructor. Robert Pickett via Getty Images.

However, these pesticides have significant limitations. These chemicals are also highly toxic to animals such as cats and horses and can also poison humans. Varroa, ever a dynamic foe, has also developed resistance to amitraz and other acaricides. These challenges, in light of ongoing bee colony losses, have sounded the alarm for researchers to help beekeepers figure out alternative strategies to fight the Varroa threat, and several are answering the call.

Vincent Ricigliano and his team at the USDA Agricultural Research Service focused on one of Varroa’s defense mechanisms against pesticides – specifically, a gene that codes for a protein transporter that helps Varroa and other arthropods clear toxic substances their system. Using RNA interference (RNAi), or a “gene silencing” technique, they were able to shut down one of Varroa’s detox mechanism so that amitraz could stay in their system. This technique helped increase the efficacy of amitraz, while importantly, the honeybees exposed to the dsRNA substance were not affected. They published their results in Parasites and Vectors earlier this year. You can also listen to Dr. Ricigliano talk about his work on the Beekeeping Today Podcast.

Another group of researchers tested a potential, entirely new alternative. Volker Herzig and his team looked to Varroa’s natural predators, venomous spiders. In their article published in npj Drug Discovery, they describe how they exposed Varroa mites to venoms from the Tasmanian cave spider and the Giant Japanese funnel web-spider and found encouraging effectiveness in killing the Varroa without affecting the bees.

Yet another research group turned to the kitchen cabinet.* They exposed Varroa to a bay leaf essential oil through a nanoemulsion, a novel drug delivery technique that uses nano-meter size carriers to more effectively bind drugs – or in this case, toxins – to their cellular targets. The method showed promising results, which were published in BMC Veterinary Research, and so offered a starting framework for a more organic possible alternative to amitraz.

A long road lies ahead in the battle against Varroa destructor. In the few short decades of this parasitic relationship, industrial beekeeping has created a feast for Varroa mites, and Varroa has mastered its infestation strategies to match the most vulnerable points in the honeybee’s life cycle. While other bee species have developed mechanisms to fight off Varroa after centuries or millennia of co-evolution, the Western honeybee has no defenses in its mere 60 years of exposure. Scientists are playing a fast catch-up game in the battle against a highly adapted parasite.

What are some things you can do to support wild honeybee populations in your area? The best way to help is to support honeybee habitats:

  • Plant flowers and other pollinator-friendly plants outdoors
  • Let “weeds” such as dandelion, clover, and goldenrod grow wild in the spring and fall
  • Avoid the use of pesticides in your garden
  • Support beekeepers by purchasing locally produced honey and beeswax products

* Thanks to @Blythe Terry for sharing this article with the BMC Collections Management and Acquisition Team Journal Club!

 

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Life Sciences > Biological Sciences > Microbiology > Parasitology
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