The involvement of ABC transporters in the resistance to permethrin insecticide in the malaria vector Anopheles stephensi

More than half of the world population lives under the risk of contracting hilnesses carried by mosquitoes. In particular 3.2 billion people in 96 countries and territories are at risk of getting malaria. Vector control through insecticides is a main component of vector-borne diseases control programs, but the continuous and increasing use of chemicals led to resistance insurgence in different vector species. Understanding the molecular mechanisms of cellular defense against xenobiotic compounds is one of the major goals for entomology to develop strategies based on the inhibition of these defenses. Several studies have drawn attention to the implication of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps located in the cellular membrane in both prokaryotic and eukariotic organisms. ABC transporters have been subdivided in eight subfamilies, from ABC-A to ABC-H, and they can carry a wide variety of substrates across cellular membranes. As a result of bioassays, analysis of trascriptome and gene expression, RNA interference, we report the involvement of specific ABC transporters (in particular the ABC-B, ABC-C and ABC-G subfamilies) in the defense of Anopheles stephensi larvae against permethrin, and the timing of their response in terms of gene expression. Indeed, the inhibition of ABC-transporters using a specific inhibitor (verapamil) led to a higher susceptibility of larvae to insecticide, indicating that specific ABC transporters are associated with insecticide detoxification. This is the first study reporting the involvement of ABC trasporters in larval defense against the insecticide permethrin in An. stephensi.