Insecticides often act on one or more locations within the insect nervous system, but it can be difficult to determine which target location is responsible for the insecticidal properties. Mode of action (MoA) studies highlight the most efficacious insecticide targets and allow for informed insecticide design. The enzyme acetylcholinesterase (AChE) is responsible for breaking down acetylcholine in nerve synapses. Acetylcholine is an excitatory neurotransmitter and must be maintained at proper concentrations to maintain physiological functions. AChE inhibition, the primary MoA of some synthetic insecticides, leads to overstimulation of the insect’s nervous system, causing muscle twitching, convulsions, paralysis, and eventually death. The yellow fever mosquito,<i> Aedes aegypti</i>, is a vector of multiple debilitating diseases including dengue fever, Zika fever, and chikungunya. Synthetic insecticides are commonly used to prevent the spread of disease and control mosquito populations. Some mosquito populations have developed resistance to synthetic insecticides, thereby diminishing synthetic insecticide effectiveness and prompting a search for alternatives. Natural products such as terpenes have shown promise as insecticides, but the MoA remains unclear. Here we explore the ability of terpenes and a new class of natural insecticides to inhibit acetylcholinesterase in adult mosquitoes. Enzymes obtained from adult mosquitoes are used to simulate acetylcholinesterase inhibition in a modified version of Ellman’s assay. The experimental setup was used to screen various other natural products and known acetylcholinesterase inhibitors for inhibitory properties. We conclude that, while these natural products show some inhibitory potential on mosquito acetylcholinesterase, this is unlikely to be the primary mode of action by which they are active as insecticides.

Determining insecticidal mode of action: Terpenes and a new class of natural insecticides inhibit adult mosquito acetylcholinesterase

ACS Fall 2020 Virtual Meeting

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