Unveiling Molecular\nMechanisms Mediating Coumaphos\nTolerance in Western Honey Bees (Apis mellifera)

Honey bees (Apis mellifera) are\nmanaged pollinators playing a critical role in global agriculture.\nAmong factors linked to bee decline, the ectoparasitic varroa mite\n(Varroa destructor) is a major stressor.\nCoumaphos is an organophosphate pro-insecticide known for its selectivity\ntoward honey bees, rendering it an effective in-hive treatment against\nvarroa mites. This study investigated the molecular mechanisms underlying\ncoumaphos tolerance in honey bees. Coumaphos-oxon inhibition studies\nwith recombinantly expressed acetylcholinesterases of bees and mites\nprecluded toxicodynamic reasons for the observed selectivity. Synergist\nbioassays and biochemical studies confirmed that honey bee CYP9Q2\nis a key enzyme involved in coumaphos detoxification, particularly\nby its catalytic capacity to hydroxylate coumaphos-oxon. Bioassays\nwith transgenic Drosophila expressing\nCYP9Q2 validated our molecular findings. Enzyme inhibition studies\nrevealed suicide substrate properties for coumaphos leading to the\ninactivation of P450s during coumaphos oxidation. This study demonstrated\nthe complexity of P450-mediated coumaphos activation and inactivation\ndriving honey bee selectivity.