From Global to Local—New Insights into Features of Pyrethroid Detoxification in Vector Mosquitoes

Abstract

The threat of mosquito-borne diseases continues to be a problem for public health in subtropical and tropical regions of the world; in response, there has been increased use of adulticidal insecticides, such as pyrethroids, in human habitation areas over the last thirty years. As a result, the prevalence of pyrethroid-resistant genetic markers in natural mosquito populations has increased at an alarming rate. This review details recent advances in the understanding of specific mechanisms associated with pyrethroid resistance, with emphasis on features of insecticide detoxification and the interdependence of multiple cellular pathways. Together, these advances add important context to the understanding of the processes that are selected in resistant mosquitoes. Specifically, before pyrethroids bind to their targets on motoneurons, they must first permeate the outer cuticle and diffuse to inner tissues. Resistant mosquitoes have evolved detoxification mechanisms that rely on cytochrome P450s (CYP), esterases, carboxyesterases, and other oxidation/reduction (redox) components to effectively detoxify pyrethroids to nontoxic breakdown products that are then excreted. Enhanced resistance mechanisms have evolved to include alteration of gene copy number, transcriptional and post-transcriptional regulation of gene expression, as well as changes to cellular signaling mechanisms. Here, we outline the variety of ways in which detoxification has been selected in various mosquito populations, as well as key gene categories involved. Pathways associated with potential new genes of interest are proposed. Consideration of multiple cellular pathways could provide opportunities for development of new insecticides.

In Vitro and In Vivo Validation of CYP6A14 and CYP6N6 Participation in Deltamethrin Metabolic Resistance in Aedes albopictus

“…12,13 Mosquitoes have been found to be metabolically resistant to several insecticides used in public health programs, such as pyrethroids, organophosphorus, carbamates, and organochlorines. 14,15 In cases of metabolic resistance, mosquitoes prevent or slow down the arrival of insecticides to the target site by metabolic detoxification, isolation, or accelerated excretion involving enhanced expression and activity of relevant metabolic detoxification enzymes. 15 Metabolic detoxification enzymes in insects, which can function independently or synergistically, include primarily cytochrome P450 (CYP450), carboxylesterase, glutathione S-transferase (GST), ABC transporter, and uridine diphosphate glycosyltransferase proteins.…”

“…14,15 In cases of metabolic resistance, mosquitoes prevent or slow down the arrival of insecticides to the target site by metabolic detoxification, isolation, or accelerated excretion involving enhanced expression and activity of relevant metabolic detoxification enzymes. 15 Metabolic detoxification enzymes in insects, which can function independently or synergistically, include primarily cytochrome P450 (CYP450), carboxylesterase, glutathione S-transferase (GST), ABC transporter, and uridine diphosphate glycosyltransferase proteins. [16][17][18][19] In mosquitoes, CYP450 proteins participate in a series of physiological and biochemical reactions, including the regulation of endogenous substances such as hormones and steroids and metabolic detoxifying exogenous substances such as pesticides and plant toxins.…”

“… 12 , 13 Mosquitoes have been found to be metabolically resistant to several insecticides used in public health programs, such as pyrethroids, organophosphorus, carbamates, and organochlorines. 14 , 15 …”

Evidence for the Participation of Chemosensory Proteins in Response to Insecticide Challenge in Conopomorpha sinensis

“…This task is performed by odorant binding proteins (OBPs) in vertebrates and two small soluble protein families, OBPs and chemosensory proteins (CSPs), in insects . CSPs were first discovered in Drosophila melanogaster in 1994, and they have been found in many insect species since then. , Due to their specificity in insects, the miscellaneous functions of CSPs are thought to be abundant in insects . A large number of studies have shown that insect CSPs can detect and selectively bind to volatiles, chemical compounds, and sex pheromone analogues in the external environment, as well as solubilize and carry endogenous hormones and nutrients …”

The interplay between malaria vectors and human activity accounts for high residual malaria transmission in a Burkina Faso village with universal ITN coverage

“…: the L1014F mutation), increased metabolic detoxi cation activity/e cacy (e.g. P450 monooxygenases), cuticular thickening or changing in hydrocarbon content and binding/sequestration mechanisms [19][20][21][22][23][24][25][26][27][28][29][30]. Furthermore, some vector species exhibit different forms of behavioural resistance (or behavioural plasticity) comprising changes in biting behaviour that facilitate the avoidance of the insecticidal barrier, such as exibility in the spectrum of host choice (opportunistic behaviour) and/or blood feeding at places and times when humans are less likely to be protected by nets (i.e.…”