Most currently used pesticides in agricultural applications contain broad-spectrum chemicals, which are harmful to a wide range of insects. However, the majority of insects are not pests, and with concerns about global insect declines and the impact this will have on ecosystem health1, there is a need for more environmentally friendly insecticides that have selective action against major pests while preserving the health of beneficial insects.
Honey bees often top the list of beneficial insects, given that thirty per cent of global agricultural systems are reliant on pollination by bees. However, the health of honey bees is increasingly under threat due to the spread of pests and diseases, including the parasitic mite Varroa destructor and other in-hive pests such as the small hive beetle. Broad-spectrum pesticides used in agriculture also contribute to declines in pollinator health2.
The recent arrival of Varroa on Australian shores has caused widespread concern to the beekeeping and horticultural industries, leading to a hive euthanasia program and feral colony baiting in the affected regions as part of the eradication response. This event was a stark reminder of the importance of maintaining current, effective pest control strategies for mites. Pesticides used to control mites elsewhere in the world are dwindling in efficacy due to the development of chemical tolerance3, and novel control methods are urgently required to safeguard the pollination and horticultural industries. In particular, a selective pesticide that was harmful to Varroa but safe for honey bees would provide a valuable weapon in our arsenal of strategies to combat mites.
How are new insecticides discovered?
In the past, insecticides were identified serendipitously via toxicity screening, with the aim to find chemicals that were lethal to insects, but not to mammals, fish or birds. Once identified, as long as a chemical effectively killed pests, little attention was given to how that chemical killed pests. Insecticides generally work by entering the insect via the gut, respiratory system or through their hard, shell-like external cuticle, and binding to a specific protein ‘target’, causing that target to malfunction in some way. Often, the protein target of early insecticides was not known until the insecticide stopped working, usually due to a genetic mutation in the target site leading to insecticide resistance. Many targets have been identified by studying insects with resistance mutations, but by this stage it is too late – once resistance develops, any insecticide with a similar chemical structure is no longer effective. We now know that most broad-spectrum insecticides are neurotoxic, affecting a range of different protein targets in the peripheral and central nervous systems of the insect, causing paralysis and death. However, in principle any target that provides an essential function to an insect is a potential avenue for insecticide discovery.
Designing pesticides that kill one group of insects but not others is a relatively new area of research, but it draws upon the principles of modern drug discovery that are used to identify new pharmaceuticals. Such methods combine toxicology and chemistry with structural biology, protein biochemistry and genomics, to identify chemical molecules that bind to promising biological targets. The key difference to this approach – target-based drug discovery – is that we already know the target. In the insect world, an ideal target is one that performs an essential biological function, but is subtly different between insects, providing potential for selective insecticide design. Once a target is in hand, high throughput screening of an extensive library of chemicals is performed to identify candidate molecules, which are then optimised to increase affinity and selectivity.
Current research
Our research at the University of Sydney, led by Prof Joel Mackay, Prof Ron Hill and Dr Emily Remnant are funded by Horticulture Innovation Australia and a generous philanthropic donation, aims to identify a selective pesticide that targets the Varroa mite but is harmless for honey bees. Although mites are from a different class to insects (the arachnids), they contain similar pathways and processes that can be targeted by insecticides. However, these processes are slightly different in honeybees, and we are looking at these differences to find a pesticide that kills mites, but not bees.
We have already identified a promising target that is part of the insect and mite hormonal system. Insect hormones regulate many major developmental processes affecting insect reproduction, development and behaviour. These hormones bind to receptors that vary subtly in structure between insect groups, providing an opportunity for selective pesticide design.
We are currently working to determine differences in the three-dimensional shapes of the Varroa and honey bee hormone receptor proteins, to find molecules that can exploit those differences. We are also working on identifying a selective insecticide for the small hive beetle, another major hive pest that thrives in the humid conditions of Australia’s east coast. While current beetle traps are effective, they incorporate a broad-spectrum insecticide, fipronil, which is highly toxic for bees if exposed. For example, if a hive takes on water and floods the trap, the neurotoxic chemical can be released into the hive and is lethal to bees. Our aim is to generate mite and beetle-specific chemicals that can be used within the hive environment to help control pests, while maintaining the health of honey bee and improving outcomes for the beekeeping and pollination industries.
Safer insecticides can be developed by targeting a hormone receptor that is specific to the target pest. This requires a number of steps including toxicology and safety testing before a product can be developed and released.
Acknowledgements
- Protecting pollinators from pesticides: Developing safer, selective pesticides targeting Varroa mite and small hive beetle hormone receptors is funded by the Hort Frontiers Pollination Fund, part of the Hort Frontiers strategic partnership initiative developed by Hort Innovation, with co-investment from the University of Sydney and contributions from the Australian Government.
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- Wagner DL, Grames EM, Forister ML, Berenbaum MR, Stopak D. (2021) Insect decline in the Anthropocene: Death by a thousand cuts. PNAS. 118 (2):e2023989118. (doi:10.1073/pnas.2023989118)
- Goulson D, Nicholls E, Botías C, & Rotheray EL (2015) Bee declines driven by combined stress from parasites, pesticides, and lack of flowers. Science. 347(6229):1255957.
- Jack CJ, Kleckner K, Demares F, Rault LC, Anderson TD, Carlier PR, Bloomquist JR & Ellis JD (2022) Testing new compounds for efficacy against Varroa destructor and safety to honey bees (Apis mellifera). Pest Manag Sci. 78(1):159-165.
- This article was peer-reviewed by Michael Holmes and Nadine Chapman.
