Mosquitoes affect millions of people worldwide because of their ability to vector disease.  There are two general approaches to reduce the risk of mosquito-borne diseases including personal protective measures and area-wide chemical interventions. The mosquito central nervous system is a proven target site for high efficacy insecticides; however, widespread resistance and inefficient target-site delivery limits the use of these insecticides to reduce the risk of mosquito-vectored diseases.  Thus, insecticide resistance and target-site delivery are serious public health challenges that warrant the development of improved chemical interventions for mosquitoes. The ATP-binding cassette (ABC) transporters are integral membrane proteins at the mosquito blood-brain barrier interface that act as molecular “vacuum cleaners” to traffic out insecticides and reduce the intracellular delivery of these chemistries to their intended target sites. The data presented here will provide evidence of a blood-brain barrier obstacle for the intracellular delivery of insecticides to the mosquito central nervous system. A series of chemodulators will be reported to enhance the target-site activity and toxicity of insecticides to susceptible and resistant mosquitoes as will the intracellular target-site delivery of these chemistries via increased ABC transporter-ATPase hydrolysis and gene expression.  The sequence-specific gene silencing of ABC transporters, with RNA interference, will show improved efficacy of the insecticides to the mosquitoes.  A functional ABC transporter cell line has been developed and will be discussed not only as a tool to identify conventional insecticides as substrates for ABC transporters in mosquitoes, but as an innovative approach to screen drug libraries for ABC transporter inhibitors that can serve as alternative chemical interventions for these vectors of disease.

Overcoming insecticide resistance: Inhibiting ABC transporters as a means of increasing insecticide efficacy

254th National Meeting (2017)

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