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-glycoprotein is an efflux transporter that assists in maintaining the blood-brain barrier interface of mosquitoes and may serve as a first line of defense to insecticide exposures. Previous studies have demonstrated the blood-brain barrier of insects interferes with the target-site action of insecticides; however, the interaction of mosquito P-glycoprotein towards these chemistries is unclear. This research study is focused on the toxicological, biochemical, and molecular characterization of mosquito P-glycoprotein as a first step towards the identification of efflux transporter interactions and the validation of a potential resistance mechanism against insecticide exposures. Here, we will provide a: 1) toxicological analysis of tacrine and bis(7)-tacrine (acetylcholinesterase inhibitors) for mosquitoes alone and in combination with verapamil (P-glycoprotein inhibitor); 2) biochemical analysis of acetylcholinesterase for mosquitoes exposed to these chemistries; and 3) molecular analysis of P-glycoprotein in these mosquitoes. The long term goal of this research study is to provide a better understanding of chemomodulators that might be used to enhance the effectiveness of established and experimental insecticides that are substrates for mosquito P-glycoprotein.

Synergistic effects of verapamil on tacrine toxicity to vector mosquitoes

246th National Meeting (2013)

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