Targeting insect xenobiotic defense transporters for precision pest control and pollinator protection

All organisms have developed cellular and molecular defense systems to combat toxic insult from xenobiotic compounds. Multidrug-resistance (MDR) transporters of the ABC-family, such as ABCB1, typically act as a first line of defense at biological barriers to expel toxic xenobiotics before they can enter and cause harm to the organism. In many insects, the multidrug resistance protein homolog 49 (MDR49) is the ABCB1 ortholog and has been shown to confer resistance to broad-spectrum insecticides in fruit flies and mosquitos. However, it is unknown to what extent the ABCB1 orthologs in beneficial pollinator insects can recognize and eliminate toxic pesticides. In this perspective, we will discuss current and emerging threats to honeybee health through unintentional chemical co-exposures and explore strategies for identifying and predicting chemical uptake and toxicities in the bee. Using the evolutionarily conserved drug efflux transporter ABCB1 (MDR49) as an example, we propose novel approaches that use structure-function analysis across insect MDR transporters to inform sustainable pest management and precision pesticide application with the goal of preserving beneficial insect pollinator health.