ABC transporters are transmembrane proteins that use ATP in order to move substrates across a membrane. Those transporters are critical for the defense of sensitive tissues against drugs and poison, as they will pump those out of the cells. In the case of pest insects, this protection is unfortunate, as it can lead to resistance to an insecticide. A high portion of tolerance due to ABC transporters is most likely due to increases in the number of ABC transporters produced by a cell. Since ABC-transporters can pump a wide variety of substrate across the membrane it is believed to be a major contributor to multi-drug resistance, meaning the organism becomes simultaneously resistant to a wide array of chemicals.
It is not even limited to insects! P-glycoprotein is a well-known ABC transporters that has been linked with multidrug resistance in cancer patients.
In the case of insecticides, ABC transporters prevent the insecticide from reaching its target by pumping the toxin out of the cell in to the insect hemolymph. This keeps the cell toxicity low allowing for the insect’s enzymes to break down the remaining toxins. Once inside the insects’ hemolymph the toxins are then filtered out by the malpighian tubule, and stored in the hind gut before being excreted.
Dr. Hawthorne illustrated multi-drug resistance using the CPB and insecticide trials done by Dr. Galen Dively. CPB are famous for “being resistant to everything”, but actually this varies across populations. In the trials, resistant and sustainable populations of CPB were exposed to a brand new type of insecticide (that neither population had experienced before), and their LD 50’s were compared. In all cases the eastern populations had a higher level of resistance, indicating a pattern that may be due to multidrug resistance that may have arisen from past exposure to another unrelated insecticide.
To test the link with ABC transporters, Dr, Hawthorne described bioassays of the CPB testing sensitivity of this insect to imidacloprid in the presence or absence of an inhibitor of the transporters. If the transporters are inhibited, they cannot carry on their detoxification function. The bioassays confirmed the role of ABC transporters by showing that, in the presence of the inhibitor, resistant populations increased their sensitivity to levels similar to those of the susceptible populations.
Dr. Hawthorne’s perspective of this mechanism shifted when he considered it in relation to the pollinator crisis and in particular CCD in honey bees.
Beneficial insects are also exposed to insecticides, and rarely just one at a time. The mechanism of multi drug resistance and ABC transporter inhibition could provide cues as to whether combinations of toxins could be a threat to beneficial insects.
Bioassays showed that the mortality resulting from exposure to coumaphos and fluvalinate (2 products used in the hives by the beekeepers trying to get rid of a parasite of the honey bees) increases in presence of a known inhibitor. Because of the generality of ABC transporters, a high number of chemicals can be processed as substrate but it is also probable that many chemicals can act as inhibitors as well.
Identifying which chemicals can act as inhibitors of ABC transporter is critical to identify risky combinations of chemicals and improve the Honey Bee risk assessment. This rejoins an earlier entry in the UMD Entomology Colloquium series (Grace Kunkel) that described the use of a fluorescent dye shown to be a substrate of ABC transporter and with which potential inhibitors could be tested.
Emily Zobel is an MS student in Cerruti Hooks’ Lab. She is currently studying the feeding habits of the invasive brown marmorated stink bug on vegetable crops.
Nathalie Steinhauer is a PhD student working in the vanEngelsdorp lab. She studies the risk factors associated with beekeeping management linked to increased honey bee colonies mortality.