ABC transporter drugs modulate IRS and ITN insecticide activity to malaria mosquitoes

Malaria is a life-threatening disease resulting from Plasmodium spp. transmission through the bite of an infected female Anopheles spp. mosquitoes. The World Health Organization recommends indoor residual spraying (IRS) of insecticides and insecticide-treated nets (ITNs) for protection against malaria mosquitoes. These insecticides are delivered via tarsal contact and, then, move across the blood-brain barrier to target the mosquito nervous system. The repeated use of insecticides can lead to metabolic and target-site resistance and, thus, compromise the efficacy of IRS and ITN approaches for reducing malaria mosquito populations. The ATP-binding cassette (ABC) transporters act as efflux and influx pumps to transport exogenous and endogenous substrates across the blood-brain barrier to the nervous system. It is reported that ABC transporters can reduce the delivery of insecticides to their intended target sites in mosquitoes. This study focuses on a series of ABC transporter activating and inactivating drugs to modulate the toxicity and efficacy of insecticide active ingredients to malaria mosquitoes. These data will be discussed in terms of screening drug libraries for ABC transporter modulators to serve as inclusions to IRS and ITN products to sustain their efficacy and longevity for reducing mosquito populations and, ultimately, the community transmission of malaria.