Declined oxidative bioactivation is attributable to selective resistance to coumaphos in honey bees

Apis mellifera, the western honey bee, is the most important pollinator in agriculture. Varroa destructor, an ectoparasitic mite that feeds on honey bees and transmits several viral infections to them, has been a significant hazard to honey bees. The most effective way to control the varroa mite is to use miticidal chemicals. However, only a few synthetic miticides, such as fluvalinate, amitraz, and coumaphos, that match the criterion of high selectivity for varroa mites with greatly reduced toxicity to honey bees are currently available for in-hive treatment. The goal of this study was to compare the toxicodynamic and metabolic natures of coumaphos between honey bees and varroa mites. To elucidate the molecular basis of the selective coumaphos toxicity, we first analyzed and compared the toxicodynamic properties of AChEs from honey bees and varroa mites. We then compared the differences in coumaphos metabolism with a particular focus on the differential detoxification and bioactivation of coumaphos between the two species by analyzing the tissue distribution of representative P450s, the quantitative and qualitative profiles of coumaphos metabolites, and the functional properties of representative P450s in each species. Finally, we tested the hypothesis that the expression induction of the P450 responsible for coumaphos bioactivation in varroa mites by several phytochemicals can increase the varroa mite-specific toxicity of coumaphos. Thus, possible exploration of the selective bioactivation mechanism in varroa mites was further discussed for developing novel synergists or/and other proinsecticides with varroacidal activity.