BY SHAHNAZ SULTANA, EMILY REMNANT, RON HILL AND JOEL MACKAY
SCHOOL OF LIFE AND ENVIRONMENTAL SCIENCES, THE UNIVERSITY OF SYDNEY

Of the 100 crop varieties that provide 90 percent of the world’s food, 71 are pollinated by bees¹. However, the recent invasion of Varroa destructor, a mite that parasitises honeybees, has led to thousands of hives to being burned, seriously impacting the livelihood of beekeepers and threatening the productivity of horticultural industries².

As part of an effective strategy to deal with this incursion, more specific and effective pesticides would be a valuable weapon. However, most pesticides currently used in agricultural applications work non-selectively against both pests and beneficial arthropods. A selective pesticide that is harmful to Varroa but safe for honeybees would therefore provide a valuable weapon in our arsenal and might also be a starting point for the development of pesticides that target other harmful mites.

In order to design pesticides that display significant selectivity, a target-based approach can be employed. This strategy leverages protein biochemistry, genomics, structural biology, toxicology and chemistry to identify molecules that interact with specific biological targets. In this context, a hormone binding protein in the Varroa mite known as the ecdysone receptor protein is a
promising target for pesticide development.

This protein interacts with the pest hormone ecdysone to regulate mite development, reproduction and behaviour³. Disruption of this interaction by designed chemicals would significantly impair mite development and reproduction,4 meaning that such chemicals could be potent pesticide candidates. Also, because this receptor is absent from vertebrates and is also subtly different between insects, chemicals targeting this receptor would be safe for farm workers, consumers and also beneficial insects such as honeybees. Such chemicals can also be applied in conjunction with current insecticides to improve potency and reduce the development of resistance.

Our research at The University of Sydney, led by Prof Joel Mackay, Prof Ron Hill and Dr Emily Remnant and funded by Hort Innovation and a generous philanthropic donation, aims to develop such a selective insecticide. Already, we have made considerable progress on this quest.

We have identified and purified significant quantities of the Varroa ecdysone receptor protein and also the corresponding protein from the honeybee through a laboratory-based protein production process. We have used an array of experimental methods to demonstrate that these lab-generated receptor proteins can interact with the ecdysone hormone and can therefore be used as targets for pesticide development.

With our target in hand, we have recently commenced the search for chemicals that can hit that target. Our strategy is to search collections of thousands of commercially available chemicals to find that needle in the haystack – a chemical that potently interferes with the Varroa ecdysone receptor but does not interfere with the equivalent target in the honeybee (and so is safe for our beloved pollinators (Figure 1). Excitingly, we have already discovered several ‘hits’ – chemicals that are starting points on that journey. Time will tell whether these starting points can be honed to yield our holy grail: a pesticide that can be deployed against Varroa without harming honeybees.

Concurrently, we are using this strategy to target another pollinator pest – the small hive beetle. To date, we have already purified and characterised the hormone receptor protein from the beetle and are on track to follow in the footsteps of our Varroa work. We hope that this new approach to pesticide design offers a competitive route to the identification of safer, more selective and environmentally friendly agents for the control of insect and arachnid pests, thereby helping to protect global agricultural systems.

¹ Nabhan, G. P., & Buchmann, S. L. (1997) Services provided by pollinators. Nature’s Services: Societal dependence on natural ecosystems, 133–150.
² Goulson, D., Nicholls, E., Botías, C., & Rotheray, E. L. (2015) Bee declines driven by combined stress from parasites, pesticides, and lack of flowers. Science, 347(6229), 1255957.
³ Jack, C. J., Kleckner, K., Demares, F., Rault, L. C., Anderson, T. D., Carlier, P. R., Bloomquist, J. R., & Ellis, J. D. (2022) Testing new compounds for efficacy against Varroa destructor and safety to honeybees (Apis mellifera). Pest Management Science, 78(1), 159–165.
4 Hamaidia, K., & Soltani, N. (2016) Ovicidal activity of an insect growth disruptor (methoxyfenozide) against Culex pipiens L. and delayed effect on development. Journal of Entomology and Zoology Studies, 4(4), 183–188.