Pharmacological and Genetic Evidence for Gap Junctions as Potential New Insecticide Targets in the Yellow Fever Mosquito, Aedes aegypti

PloS One
Travis L Calkins, Peter M Piermarini

Abstract

The yellow fever mosquito Aedes aegypti is an important vector of viral diseases that impact global health. Insecticides are typically used to manage mosquito populations, but the evolution of insecticide resistance is limiting their effectiveness. Thus, identifying new molecular and physiological targets in mosquitoes is needed to facilitate insecticide discovery and development. Here we test the hypothesis that gap junctions are valid molecular and physiological targets for new insecticides. Gap junctions are intercellular channels that mediate direct communication between neighboring cells and consist of evolutionarily distinct proteins in vertebrate (connexins) and invertebrate (innexins) animals. We show that the injection of pharmacological inhibitors of gap junctions (i.e., carbenoxolone, meclofenamic acid, or mefloquine) into the hemolymph of adult female mosquitoes elicits dose-dependent toxic effects, with mefloquine showing the greatest potency. In contrast, when applied topically to the cuticle, carbenoxolone was the only inhibitor to exhibit full efficacy. In vivo urine excretion assays demonstrate that both carbenoxolone and mefloquine inhibit the diuretic output of adult female mosquitoes, suggesting inhibition o...Continue Reading

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Citations

Feb 11, 2020·Frontiers in Cellular and Infection Microbiology·Poliana Fernanda GiachettoRenato Andreotti
Oct 27, 2018·Frontiers in Physiology·Juan GüizaJosé L Vega
May 22, 2019·International Journal of Molecular Sciences·Alejandro SánchezPierre Baldi
Jan 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Pablo CabreroJulian A T Dow

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

Basic Local Alignment Search Tool ( BLAST )
Primer3
GraphPad Prism

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