Evidence for P-glycoprotein modification of insecticide toxicity in vector mosquitoes

Mosquitoes affect human health worldwide as a result of their ability to vector multiple diseases. Widespread resistance is a serious public health challenge that limits the use of high efficacy insecticides to reduce the risk of mosquito-vectored diseases.  P-glycoproteins (P-gps) are efflux transporters that assist in maintaining the blood-brain barrier interface of insects and may serve as a first line of defense to insecticide exposures. Our previous studies have demonstrated the blood-brain barrier of mosquitoes to interfere with the target-site action of established and experimental insecticides; however, the interaction of P-gps toward these chemistries is unclear. In this study, we will provide a: 1) toxicological analysis of select anticholinesterases for mosquitoes alone and in combination with inhibitory ligands of P-gps; 2) biochemical analysis of acetylcholinesterase for mosquitoes exposed to these compounds; and 3) molecular analysis of P-gps expressed in mosquitoes.