Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B.
View Article and Find Full Text PDFThe citrus red mite has developed strong resistance to acaricides. Cytochrome P450 monooxygenases (P450s) can detoxify pesticides and are involved in pesticide resistance in many insects. Here, a pyridaben-resistant strain showed cross-resistance to cyenopyrafen, bifenazate, fenpyroximate, and tolfenpyrad.
View Article and Find Full Text PDFInsecticide resistance in Panonychus citri is a major obstacle to mite control in citrus orchards. Pyrethroid insecticides are continually used to control mites in China, although resistance to pyrethroids has evolved in some populations. Here, the resistance to the pyrethroid fenpropathrin was investigated and 7 out of 8 field-collected populations of P.
View Article and Find Full Text PDFThe sustainable control of many highly damaging insect crop pests and disease vectors is threatened by the evolution of insecticide resistance. As a consequence, strategies have been developed that aim to prevent or delay resistance development by rotating or mixing insecticides with different modes of action (MoA). However, these approaches can be compromised by the emergence of mechanisms that confer cross-resistance to insecticides with different MoA.
View Article and Find Full Text PDFCytoplasmic domains frequently promote functional assembly of multimeric ion channels. To investigate structural determinants of this process, we generated the 'T1-chimera' construct of the NaChBac sodium channel by truncating its C-terminal domain and splicing the T1-tetramerisation domain of the Kv1.2 channel to the N terminus.
View Article and Find Full Text PDFResistance to pyrethroid insecticides is a major concern for malaria vector control. Pyrethroids target the voltage-gated sodium channel (VGSC), an essential component of the mosquito nervous system. Substitutions in the amino acid sequence can induce a resistance phenotype.
View Article and Find Full Text PDFThe cotton bollworm P450s of the clustered CYP6AE subfamily share high sequence identities but differ dramatically in their capacity to metabolize xenobiotics, especially esfenvalerate. Among them, CYP6AE17 has the highest sequence identity with CYP6AE18 but shows ~7-fold higher metabolic efficiency. CYP6AE11 is most active towards esfenvalerate but CYP6AE20 is inactive even though the enzymes share 54.
View Article and Find Full Text PDFThis article describes the effect of the pyrethroid insecticide deltamethrin on the cardiac voltage-gated sodium channel Nav1.5. Two concentrations of deltamethrin were used and the effects were compared with those of the sea anemone toxin ATx-II and β4-peptide, which is the C-terminus of the Nav channel β-subunit.
View Article and Find Full Text PDFThe evolution of insecticide resistance mechanisms in natural populations of Anopheles malaria vectors is a major public health concern across Africa. Using genome sequence data, we study the evolution of resistance mutations in the resistance to dieldrin locus (Rdl), a GABA receptor targeted by several insecticides, but most notably by the long-discontinued cyclodiene, dieldrin. The two Rdl resistance mutations (296G and 296S) spread across West and Central African Anopheles via two independent hard selective sweeps that included likely compensatory nearby mutations, and were followed by a rare combination of introgression across species (from A.
View Article and Find Full Text PDFVoltage-gated sodium channels are responsible not only for the fast upstroke of the action potential, but they also modify cellular excitability via persistent and resurgent currents. Insecticides act via permanently opening sodium channels to immobilize the animals. Cellular recordings performed decades ago revealed distinctly hooked tail currents induced by these compounds.
View Article and Find Full Text PDFColour polymorphism is a widespread phenomenon and often encompasses different behavioural traits and strategies. More recently, it has been shown that morphs can also signal consistent individual differences (personality). An example are Gouldian finches that show discrete head colour morphs in the same population with red-headed birds being more aggressive but less risk-taking and explorative than black-headed birds in the lab.
View Article and Find Full Text PDFSodium channel blocker insecticides (SCBIs) like indoxacarb and metaflumizone offer an alternative insecticide resistance management (IRM) strategy against several pests that are resistant to other compounds. However, resistance to SCBIs has been reported in several pests, in most cases implicating metabolic resistance mechanisms, although in certain indoxacarb resistant populations of Plutella xylostella and Tuta absoluta, two mutations in the domain IV S6 segment of the voltage-gated sodium channel, F1845Y and V1848I have been identified, and have been postulated through in vitro electrophysiological studies to contribute to target-site resistance. In order to functionally validate in vivo each mutation in the absence of confounding resistance mechanisms, we have employed a CRISPR/Cas9 strategy to generate strains of Drosophila melanogaster bearing homozygous F1845Y or V1848I mutations in the para (voltage-gated sodium channel) gene.
View Article and Find Full Text PDFGlutamate-gated chloride channels (GluCls) are found only in invertebrates and mediate fast inhibitory neurotransmission. The structural and functional diversity of GluCls are produced through assembly of multiple subunits and via posttranscriptional alternations. Alternative splicing is the most common way to achieve this in insect GluCls and splicing occurs primarily at exons 3 and 9.
View Article and Find Full Text PDFProton-evoked activation of sensory neurons is counteracted by inhibition of voltage-gated Na channels, and the low acid-sensitivity of sensory neuron of the African naked mole-rat (ANMr) was reported to be due to a strong proton-evoked block of ANMrNav1.7. Here we aimed to reevaluate the role of the suggested negatively-charged motif in the ANMrNav1.
View Article and Find Full Text PDFAsparagine is conserved in the S6 transmembrane segments of all voltage-gated sodium, calcium, and TRP channels identified to date. A broad spectrum of channelopathies including cardiac arrhythmias, epilepsy, muscle diseases, and pain disorders is associated with its mutation. To investigate its effects on sodium channel functional properties, we mutated the simple prokaryotic sodium channel NaChBac.
View Article and Find Full Text PDFDisulfide bridges are side-chain-mediated covalent bonds between cysteines that stabilize many protein structures. Disulfide mapping experiments to resolve these linkages typically involve proteolytic cleavage of the protein of interest followed by mass spectroscopy to identify fragments corresponding to linked peptides. Here we report the sequence-based "DIMPL" web tool to facilitate the planning and analysis steps of experimental mapping studies.
View Article and Find Full Text PDFAbamectin is one of the most widely used avermectins for agricultural pests control, but the emergence of resistance around the world is proving a major threat to its sustained application. Abamectin acts by directly activating glutamate-gated chloride channels (GluCls) and modulating other Cys-loop ion channels. To date, three mutations occurring in the transmembrane domain of arthropod GluCls are associated with target-site resistance to abamectin: A309V in Plutella xylostella GluCl (PxGluCl), G323D in Tetranychus urticae GluCl1 (TuGluCl1) and G326E in TuGluCl3.
View Article and Find Full Text PDFThe pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel.
View Article and Find Full Text PDFMutations in the voltage-gated sodium channel Nav1.7 are linked to inherited pain syndromes such as erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). PEPD mutations impair Nav1.
View Article and Find Full Text PDFWe describe the identification in aphids of a unique heterodimeric voltage-gated sodium channel which has an atypical ion selectivity filter and, unusually for insect channels, is highly insensitive to tetrodotoxin. We demonstrate that this channel has most likely arisen by adaptation (gene fission or duplication) of an invertebrate ancestral mono(hetero)meric channel. This is the only identifiable voltage-gated sodium channel homologue in the aphid genome(s), and the channel's novel selectivity filter motif (DENS instead of the usual DEKA found in other eukaryotes) may result in a loss of sodium selectivity, as indicated experimentally in mutagenised Drosophila channels.
View Article and Find Full Text PDFThe human voltage-gated sodium channel Nav1.7 plays a crucial role in transmission of noxious stimuli. The inherited pain disorder erythromelalgia (IEM) has been linked to Nav1.
View Article and Find Full Text PDFInherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.
View Article and Find Full Text PDFBackground: The pyrethroid insecticides are a very successful group of compounds that target invertebrate voltage-gated sodium channels and are widely used in the control of insects, ticks and mites. It is well established that some pyrethroids are good insecticides whereas others are more effective as acaricides. This species specificity is advantageous for controlling particular pest(s) in the presence of another non-target invertebrate, for example controlling the Varroa mite in honeybee colonies.
View Article and Find Full Text PDFBisphenol A (BPA) has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-gated sodium channel subtype expressed in the human heart.
View Article and Find Full Text PDFNeonicotinoid insecticides target nicotinic acetylcholine receptors (nAChR) in the nervous system of insects but are largely ineffective against ticks. This study aimed to identify the molecular basis for this insensitivity. A homology model of the nAChR binding domain was generated on the basis of the crystal structure of an acetylcholine-binding protein with the insecticide imidacloprid bound.
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