Neurotoxicity and mode of action of fluralaner on honeybee Apis mellifera L.

Abstract

BACKGROUND: Fluralaner, a novel pesticide that targets the -aminobutyric acid (GABA) receptor (GABAR) subunit of resistant to dieldrin (RDL), exhibits strong potential to be an insecticide to control agricultural insect pests. However, the risk and action of fluralaner to economic insects, e.g., honeybee Apis mellifera Linnaeus, remains unclear. RESULTS:In this study, both oral and contact toxicity of fluralaner to honeybee were found to be 0.13 g adult -1 . Abamectin, dieldrin, ethiprole, -endosulfan, fipronil and fluralaner strongly inhibited the GABA-induced current in A. mellifera RDL (AmRDL), expressed in Xenopus laevis oocytes, with median inhibitory concentration (IC 50 ) values of 7.99, 868.1, 27.10, 412.0, 11.21 and 13.59 nM, respectively. The binding free energy and electrophysiological response of AmRDL and insecticides were opposite. The correlation values between toxicity (to A. mellifera) and binding free energy/electrophysiological inhibition (to AmRDL) were at a moderate level. CONCLUSION:In conclusion, we report for the first time the notable risk of fluralaner to honeybee in vivo and compared the actions of GABAR-targeted insecticides on the AmRDL receptor.

Distinct roles of two RDL GABA receptors in fipronil action in the diamondback moth (Plutella xylostella)

“…(2019), who found that introducing the A2′S mutation into Px RDL1 of susceptible P. xylostella only caused an approximately 3‐fold increase in fipronil resistance. Molecular docking analyses demonstrated that the 6′ amino acid residue is critical for the combination of insect RDL receptors and insecticides, such as fipronil, ethiprole, and dieldrin (Zheng et al ., 2014; Sheng et al ., 2019). The T6′L mutation in Rhipicephalus microplus RDL was detected in fipronil‐ and dieldrin‐resistant strains (Hope et al ., 2010; Janer et al ., 2019).…”

Novel alternative splicing of GABA receptor RDL exon 9 from Laodelphax striatellus modulates agonist potency

“…Fluralaner (≥95%) was purified from BRAVECTO ® Chew tablet (Merck & Co., Inc., Isando, South Africa) and verified as previously described (Sheng et al ., 2017; Sheng et al ., 2019). GABA and ethiprole (>98%) were purchased from J & K Scientific Ltd. (Beijing, China).…”

Molecular Targets of Neurotoxic Insecticides in Apis mellifera

“…[101] In molecular modelling of RDL subunits from different species (including Apis mellifera) fipronil is erected in the channel pore surrounded by the five M2 segments, the trifluoromethyl group being oriented toward the intracellular compartment. [75,102,103] The binding site of fipronil is located between L9' (which defines the narrowest point of the pore) and P-2', with A2' and T6' critically involved in direct interaction with phenylpyrazole. [75] Lack of conservation of these two residues probably explains the weaker sensitivity of mammalian GABA A for fipronil compared to insect RDL.…”

“…[75,102,103] The binding site of fipronil is located between L9' (which defines the narrowest point of the pore) and P-2', with A2' and T6' critically involved in direct interaction with phenylpyrazole. [75] Lack of conservation of these two residues probably explains the weaker sensitivity of mammalian GABA A for fipronil compared to insect RDL. [104] Meta-diamides are similarly efficient on a Drosophila melanogaster RDL mutant harboring substitutions at both A2' and T6' than on wild type receptor.…”