Unravelling the Molecular Determinants of Bee Sensitivity to Neonicotinoid Insecticides

Abstract

SummaryThe impact of neonicotinoid insecticides on the health of bee pollinators is a topic of intensive research and considerable current debate [1]. As insecticides, certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and thiamethoxam, are as intrinsically toxic to bees as to the insect pests they target. However, this is not the case for all neonicotinoids, with honeybees orders of magnitude less sensitive to N-cyanoamidine compounds such as thiacloprid [2]. Although previous work has suggested that this is due to rapid metabolism of these compounds [2, 3, 4, 5], the specific gene(s) or enzyme(s) involved remain unknown. Here, we show that the sensitivity of the two most economically important bee species to neonicotinoids is determined by cytochrome P450s of the CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids does not reside in differences in their affinity for the receptor but rather in divergent metabolism by P450s. Functional expression of the entire CYP3 clade of P450s from honeybees identified a single P450, CYP9Q3, that metabolizes thiacloprid with high efficiency but has little activity against imidacloprid. We demonstrate that bumble bees also exhibit profound differences in their sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid sensitivity in this species. Our results demonstrate that bee pollinators are equipped with biochemical defense systems that define their sensitivity to insecticides and this knowledge can be leveraged to safeguard bee health.

Caste‐ and pesticide‐specific effects of neonicotinoid pesticide exposure on gene expression in bumblebees

“…A previous study reported that expression of cytochrome P450 genes, a family of genes typically involved in chemical detoxification, is affected by imidacloprid in honeybees (Chaimanee, Evans, Chen, Jackson, & Pettis, ). In line with this, two cytochrome P450 CYP9Q subfamily genes in bumblebees metabolize the neonicotinoid thiacloprid but not imidacloprid (Manjon et al, ). Intriguingly, we found no effect of neonicotinoid exposure on either of these genes, suggesting that the genes do not code for products that metabolize clothianidin, or that they function on different timescales or tissues than our study focused on.…”

Are honeybees suitable surrogates for use in pesticide risk assessment for non‐Apis bees?

“…Although this suggests that there might be large differences in terms of the sensitivity of distantly related species based on phylogenetics (e.g. mammals versus insects), a more recent investigation suggests that pharmacodynamics plays only a secondary role when looking at more closely related species such as bumblebees and honeybees …”

Effects of chronic dietary thiamethoxam and prothioconazole exposure on Apis mellifera worker adults and brood

“…P450s are an important part of the detoxification and defense system of insects, but this family of monooxygenases is especially limited in honey bees, which may make them more susceptible to negative effects when exposed to combinations of pesticides . The CYP9Q P450 subfamily, expressed in the brain and the Malpighian tubules, among other tissues, has been shown to detoxify the neonicotinoids thiacloprid and acetamiprid in honey bees …”