Resistance to amitraz in the parasitic honey bee mite Varroa destructor is associated with mutations in the β-adrenergic-like octopamine receptor

Abstract

Varroa destructor is considered a major reason for high loss rate of Western honey bee (Apis mellifera) colonies. To prevent colony losses caused by V. destructor, it is necessary to actively manage the mite population. Beekeepers, particularly commercial beekeepers, have few alternative treatments other than synthetic acaricides to control the parasite, resulting in intensive treatment regimens that led to the evolution of resistance in mite populations. To investigate the mechanism of the resistance to amitraz detected in V. destructor mites from French and U.S. apiaries, we identified and characterized octopamine and tyramine receptors (the known targets of amitraz) in this species. The comparison of sequences obtained from mites collected from different apiaries with different treatment regimens, showed that the amino acid substitutions N87S or Y215H in the OctβR were associated with treatment failures reported in French or U.S. apiaries, respectively. Based on our findings, we have developed and tested two high throughput diagnostic assays based on TaqMan technology able to accurately detect mites carrying the mutations in this receptor. This valuable information may be of help for beekeepers when selecting the most suitable acaricide to manage V. destructor.

Transcriptomic analysis of the honey bee (Apis mellifera) queen brain reveals that gene expression is affected by pesticide exposure during development

“…Amitraz has been the most widely used miticide to control for Varroa mites for the last 20 years, even though some studies have documented mite populations that are now resistant to amitraz in the U.S. [ 34 , 31 ], Argentina [ 101 ], Czechia [ 102 ], and France [ 103 ]. Given the importance of amitraz as the main “go-to” miticide in U.S. commercial beekeeping operations, more studies looking at the non-target effects of amitraz exposure on honey bees are needed.…”

Mechanism of enhanced sensitivity of mutated β‐adrenergic‐like octopamine receptor to amitraz in honeybee Apis mellifera: An insight from MD simulations

“…55 Resistance to amitraz has been reported worldwide, and the mechanisms responsible for the lack of efficacy have attracted extensive interest. 56,57 Previous studies have identified mutations that might associate with resistance, 22,58,59 therefore identifying the reason for the effectiveness of amitraz against Varroa mites but its low toxicity to honeybees is useful to research amitraz resistance. The key determinant of the drug efficacy of orthosteric drugs is a high affinity, and the enhanced amitraz activation of Oct⊎2R by mutations is valuable for designing more rational drugs to control Varroa mites.…”

“…Amino acid replacement of octopamine/tyramine receptors (T8P, L22S, and A181T) leading to amitraz resistance have been reported in Rhipicephalus microplus 20,21 . A more recent study evidenced that amino acid substitutions N87S or Y215H in the Octβ2R might be associated with the resistance to amitraz in V. destructor 22 . A previous study found that the relative insensitivity of honeybee Octβ2R to amitraz was vital for the application of amitraz, but combinatorial mutations (E208V, I335T, and I350V) increased the sensitivity of honeybee Octβ2R to amitraz through a pharmacological profile and transgenic flies expressing Octβ2R variants assays 18 .…”

“…20,21 A more recent study evidenced that amino acid substitutions N87S or Y215H in the Oct⊎2R might be associated with the resistance to amitraz in V. destructor. 22 A previous study found that the relative insensitivity of honeybee Oct⊎2R to amitraz was vital for the application of amitraz, but combinatorial mutations (E208V, I335T, and I350V) increased the sensitivity of honeybee Oct⊎2R to amitraz through a pharmacological profile and transgenic flies expressing Oct⊎2R variants assays. 18 Thus, resistance to amitraz was diminished for this honeybee Oct⊎2R mutant, and amitraz might produce toxicity to these honeybee mutants.…”

Eficácia Do Tratamento Combinado De Amitraz E Flumetrina No Controlo Da Varroose

“…Este ácaro foi observado pela primeira vez nas abelhas da espécie Apis cerana. Nesta espécie, as varroas causam danos ligeiros, pois o seu crescimento populacional era limitado, pois só se reproduzem nos alvéolos de zangão (Hernández-Rodríguez et al, 2022). Em meados do século XX, este ácaro passou a infestar colónias de Apis mellifera, evidenciando uma maior eficiência reprodutiva nesta espécie de abelhas, pois conseguem reproduzir-se tanto nos alvéolos de zangão como nos de obreiras (Beaurepaire et al, 2015).…”