+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Use of chemical probes to explore the toxicological potential of the K + /Cl - cotransporter (KCC) as a novel insecticide target to control the primary vector of dengue and Zika virus, Aedes aegypti

Use of chemical probes to explore the toxicological potential of the K + /Cl - cotransporter (KCC) as a novel insecticide target to control the primary vector of dengue and Zika virus, Aedes aegypti

Pesticide Biochemistry and Physiology 151: 10-17

The majority of commercialized insecticides target the insect nervous system and therefore, neural proteins are well-validated targets for insecticide development. Considering that only a few neural targets are exploited for insecticidal action and the development of insecticide resistance has reduced the efficacy of current insecticidal classes, we sought to test the toxicological potential of the potassium-chloride cotransporter (KCC). In mammals, KCC proteins have seminal roles in shaping GABAergic signaling and inhibitory neurotransmission, thus ion transport through KCC is critical for proper neurotransmission. Therefore, we hypothesized that mosquito KCC represents a putative insecticide target site and that pharmacological inhibition of KCC constructs in Aedes aegypti will be lethal. To test this hypothesis, we developed a robust, cell-based fluorescence assay that enables in vitro characterization of small-molecules against Ae. aegypti KCC and performed a proof-of-concept study employing well characterized mammalian KCC modulators to determine the toxicological potential of Ae. aegypti KCC. The selective inhibitor of mammalian KCC, termed VU0463271, was found to be a potent inhibitor Ae. aegypti KCC and microinjection induced lethality in a concentration-dependent manner to susceptible and pyrethroid resistant strains. Importantly, an analog of VU0463271 was shown to be >40-fold less potent and did not induce toxicity, suggesting that the observed physiological effects and mortality are likely due to KCC inhibition. This proof-of-concept study suggests that Ae. aegypti KCC represents a putative target site for mosquitocide design that can mitigate the current mechanisms of insecticide resistance.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 066446788

Download citation: RISBibTeXText

PMID: 30704707

DOI: 10.1016/j.pestbp.2018.03.019

Related references

Comparison of vector competence of Aedes mediovittatus and Aedes aegypti for dengue virus: implications for dengue control in the Caribbean. Plos Neglected Tropical Diseases 9(2): E0003462, 2015

Space treatments of insecticide for control of dengue virus vector Aedes aegypti in southern Mexico. I. Baseline penetration trials in open field and houses. Journal of the American Mosquito Control Association 22(2): 301-305, 2006

The impact of temperature and Wolbachia infection on vector competence of potential dengue vectors Aedes aegypti and Aedes albopictus in the transmission of dengue virus serotype 1 in southern Taiwan. Parasites and Vectors 10(1): 551, 2017

Spatial variation of insecticide resistance in the dengue vector Aedes aegypti presents unique vector control challenges. Parasites and Vectors 9: 67, 2016

Multiple insecticide resistance mechanisms in primary dengue vector, Aedes aegypti (Linn.) from dengue endemic districts of sub-Himalayan West Bengal, India. Plos one 13(9): E0203207, 2018

Control of dengue and Zika virus vector Aedes aegypti using the predatory copepod Megacyclops formosanus : Synergy with Hedychium coronarium- synthesized silver nanoparticles and related histological changes in targeted mosquitoes. Process Safety and Environmental Protection 109: 82-96, 2017

Personal Protection of Permethrin-Treated Clothing against Aedes aegypti, the Vector of Dengue and Zika Virus, in the Laboratory. Plos one 11(5): E0152805, 2016

Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti. Parasitology Research 114(9): 3315-3325, 2015

Potential for sublethal insecticide exposure to impact vector competence of Aedes albopictus (Diptera: Culicidae) for dengue and Zika viruses. Research and Reports in Tropical Medicine 8: 53-57, 2017

Identification and expression patterns of two TRPV channel genes in antennae and Johnston's organ of the dengue and Zika virus vector mosquito, Aedes aegypti. Journal of Asia-Pacific Entomology 19(3): 563-569, 2016

Assessment of insecticide resistance in primary dengue vector, Aedes aegypti (Linn.) from Northern Districts of West Bengal, India. Acta Tropica 187: 78-86, 2018

Possible jungle dengue recent studies and hypotheses distribution human primary host mosquito vector virus aedes aegypti monkey aedes albopictus. Japanese Journal of Medical Science & Biology 20(SUPP): 69-74, 1967

The enzyme 3-hydroxykynurenine transaminase as potential target for 1,2,4-oxadiazoles with larvicide activity against the dengue vector Aedes aegypti. Bioorganic and Medicinal Chemistry 21(22): 6996-7003, 2013

Alternative insecticides for larval control of the dengue vector Aedes aegypti in Lao PDR: insecticide resistance and semi-field trial study. Parasites and Vectors 11(1): 616, 2018

Assessment of Local Mosquito Species Incriminates Aedes aegypti as the Potential Vector of Zika Virus in Australia. Plos Neglected Tropical Diseases 10(9): E0004959, 2016