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Ke Dong - One of the best experts on this subject based on the ideXlab platform.
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detection of a new Pyrethroid resistance mutation v410l in the sodium channel of aedes aegypti a potential challenge for mosquito control
Scientific Reports, 2017Co-Authors: Khalid Haddi, Yoshiko Nomura, Ke Dong, Hudson V V Tome, Wilson Rodrigues Valbon, Gustavo Ferreira Martins, Eugenio E OliveiraAbstract:The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of Pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100-60,000 fold) of resistance to both type I and type II Pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain. This study is the first report of the V410L mutation in mosquitoes. Alone or in combination with the F1534C mutation, the V410L mutation drastically reduced the sensitivity of mosquito sodium channels expressed in Xenopus oocytes to both type I and type II Pyrethroids. The V410L mutation presents a serious challenge for the control of A. aegypti and will compromise the use of Pyrethroids for the control of A. aegypti in Brazil; therefore, early monitoring of the frequency of the V410L mutation will be a key resistance management strategy to preserve the effectiveness of Pyrethroid insecticides.
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molecular evidence for dual Pyrethroid receptor sites on a mosquito sodium channel
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Yoshiko Nomura, Gul Satar, Ralf Nauen, Boris S Zhorov, Ke DongAbstract:Pyrethroid insecticides are widely used as one of the most effective control measures in the global fight against agricultural arthropod pests and mosquito-borne diseases, including malaria and dengue. They exert toxic effects by altering the function of voltage-gated sodium channels, which are essential for proper electrical signaling in the nervous system. A major threat to the sustained use of Pyrethroids for vector control is the emergence of mosquito resistance to Pyrethroids worldwide. Here, we report the successful expression of a sodium channel, AaNav1–1, from Aedes aegypti in Xenopus oocytes, and the functional examination of nine sodium channel mutations that are associated with Pyrethroid resistance in various Ae. aegypti and Anopheles gambiae populations around the world. Our analysis shows that five of the nine mutations reduce AaNav1–1 sensitivity to Pyrethroids. Computer modeling and further mutational analysis revealed a surprising finding: Although two of the five confirmed mutations map to a previously proposed Pyrethroid-receptor site in the house fly sodium channel, the other three mutations are mapped to a second receptor site. Discovery of this second putative receptor site provides a dual-receptor paradigm that could explain much of the molecular mechanisms of Pyrethroid action and resistance as well as the high selectivity of Pyrethroids on insect vs. mammalian sodium channels. Results from this study could impact future prediction and monitoring of Pyrethroid resistance in mosquitoes and other arthropod pests and disease vectors.
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diversity and convergence of sodium channel mutations involved in resistance to Pyrethroids
Pesticide Biochemistry and Physiology, 2013Co-Authors: Frank D Rinkevich, Ke DongAbstract:Pyrethroid insecticides target voltage-gated sodium channels, which are critical for electrical signaling in the nervous system. The intensive use of Pyrethroids in controlling arthropod pests and disease vectors has led to many instances of Pyrethroid resistance around the globe. In the past two decades, studies have identified a large number of sodium channel mutations that are associated with resistance to Pyrethroids. The purpose of this review is to summarize both common and unique sodium channel mutations that have been identified in arthropod pests of importance to agriculture or human health. Identification of these mutations provides valuable molecular markers for resistance monitoring in the field and helped the discovery of the elusive Pyrethroid receptor site(s) on the sodium channel.
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A residue in the transmembrane segment 6 of domain I in insect and mammalian sodium channels regulate differential sensitivities to Pyrethroid insecticides
Neurotoxicology, 2013Co-Authors: Eugenio E Oliveira, Yoshiko Nomura, Ke DongAbstract:Abstract Voltage-gated sodium channels are critical for electrical signaling in the nervous system. Pyrethroid insecticides exert their toxic action by modifying the gating of sodium channels. A valine to methionine mutation in the transmembrane segment 6 of domain I (IS6) of sodium channels from tobacco budworms ( Heliothis virescens ) has been shown to alter channel gating and reduce insect sodium channel sensitivity to Pyrethroids. A valine to leucine substitution was subsequently reported in Pyrethroid-resistant bedbug populations. Intriguingly, Pyrethroid-resistant mammalian sodium channels possess an isoleucine at the corresponding position. To determine whether different substitutions at this position alter channel gating and confer Pyrethroid resistance, we made valine to methionine, isoleucine or leucine substitutions at the corresponding position, V409, in a cockroach sodium channel and examined the gating properties and Pyrethroid sensitivity of the three mutants in Xenopus oocytes. All three mutations reduced the channel sensitivity to three Pyrethroids (permethrin, cismethrin and deltamethrin). V409M, but not V409I or V409L, caused 6–7 mV depolarizing shifts in the voltage dependences of both activation and inactivation. V409M and V409L slowed channel activation kinetics and accelerated open-state deactivation kinetics, but V409I did not. Furthermore, the substitution of isoleucine with valine, but not with methionine nor leucine, at the corresponding position in a rat skeletal muscle sodium channel, rNa v 1.4, enhanced channel sensitivity to deltamethrin. Collectively, our study highlights an important role of residues at 409 in regulating not only sodium channel gating, but also the differential sensitivities of insect and mammalian sodium channels to Pyrethroids.
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a sodium channel mutation identified in aedes aegypti selectively reduces cockroach sodium channel sensitivity to type i but not type ii Pyrethroids
Insect Biochemistry and Molecular Biology, 2011Co-Authors: Yoshiko Nomura, Ke DongAbstract:Voltage-gated sodium channels are the primary target of Pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in Pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to Pyrethroids. Recently, several novel mutations were reported in sodium channel genes of Pyrethroid-resistant Aedes mosquito populations. One of the mutations is a phenylalanine (F) to cysteine (C) change in segment 6 of domain III (IIIS6) of the Aedes mosquito sodium channel. Curiously, a previous study showed that alanine substitution of this F did not alter the action of deltamethrin, a type II Pyrethroid, on a cockroach sodium channel. In this study, we changed this F to C in a Pyrethroid-sensitive cockroach sodium channel and examined mutant channel sensitivity to permethrin as well as five other type I or type II Pyrethroids in Xenopus oocytes. Interestingly, the F to C mutation drastically reduced channel sensitivity to three type I Pyrethroids, permethrin, NRDC 157 (a deltamethrin analogue lacking the α-cyano group) and bioresemthrin, but not to three type II Pyrethroids, cypermethrin, deltamethrin and cyhalothrin. These results confirm the involvement of the F to C mutation in permethrin resistance, and raise the possibility that rotation of type I and type II Pyrethroids might be considered in the control of insect pest populations where this particular mutation is present.
Yoshiko Nomura - One of the best experts on this subject based on the ideXlab platform.
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detection of a new Pyrethroid resistance mutation v410l in the sodium channel of aedes aegypti a potential challenge for mosquito control
Scientific Reports, 2017Co-Authors: Khalid Haddi, Yoshiko Nomura, Ke Dong, Hudson V V Tome, Wilson Rodrigues Valbon, Gustavo Ferreira Martins, Eugenio E OliveiraAbstract:The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of Pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100-60,000 fold) of resistance to both type I and type II Pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain. This study is the first report of the V410L mutation in mosquitoes. Alone or in combination with the F1534C mutation, the V410L mutation drastically reduced the sensitivity of mosquito sodium channels expressed in Xenopus oocytes to both type I and type II Pyrethroids. The V410L mutation presents a serious challenge for the control of A. aegypti and will compromise the use of Pyrethroids for the control of A. aegypti in Brazil; therefore, early monitoring of the frequency of the V410L mutation will be a key resistance management strategy to preserve the effectiveness of Pyrethroid insecticides.
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molecular evidence for dual Pyrethroid receptor sites on a mosquito sodium channel
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Yoshiko Nomura, Gul Satar, Ralf Nauen, Boris S Zhorov, Ke DongAbstract:Pyrethroid insecticides are widely used as one of the most effective control measures in the global fight against agricultural arthropod pests and mosquito-borne diseases, including malaria and dengue. They exert toxic effects by altering the function of voltage-gated sodium channels, which are essential for proper electrical signaling in the nervous system. A major threat to the sustained use of Pyrethroids for vector control is the emergence of mosquito resistance to Pyrethroids worldwide. Here, we report the successful expression of a sodium channel, AaNav1–1, from Aedes aegypti in Xenopus oocytes, and the functional examination of nine sodium channel mutations that are associated with Pyrethroid resistance in various Ae. aegypti and Anopheles gambiae populations around the world. Our analysis shows that five of the nine mutations reduce AaNav1–1 sensitivity to Pyrethroids. Computer modeling and further mutational analysis revealed a surprising finding: Although two of the five confirmed mutations map to a previously proposed Pyrethroid-receptor site in the house fly sodium channel, the other three mutations are mapped to a second receptor site. Discovery of this second putative receptor site provides a dual-receptor paradigm that could explain much of the molecular mechanisms of Pyrethroid action and resistance as well as the high selectivity of Pyrethroids on insect vs. mammalian sodium channels. Results from this study could impact future prediction and monitoring of Pyrethroid resistance in mosquitoes and other arthropod pests and disease vectors.
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A residue in the transmembrane segment 6 of domain I in insect and mammalian sodium channels regulate differential sensitivities to Pyrethroid insecticides
Neurotoxicology, 2013Co-Authors: Eugenio E Oliveira, Yoshiko Nomura, Ke DongAbstract:Abstract Voltage-gated sodium channels are critical for electrical signaling in the nervous system. Pyrethroid insecticides exert their toxic action by modifying the gating of sodium channels. A valine to methionine mutation in the transmembrane segment 6 of domain I (IS6) of sodium channels from tobacco budworms ( Heliothis virescens ) has been shown to alter channel gating and reduce insect sodium channel sensitivity to Pyrethroids. A valine to leucine substitution was subsequently reported in Pyrethroid-resistant bedbug populations. Intriguingly, Pyrethroid-resistant mammalian sodium channels possess an isoleucine at the corresponding position. To determine whether different substitutions at this position alter channel gating and confer Pyrethroid resistance, we made valine to methionine, isoleucine or leucine substitutions at the corresponding position, V409, in a cockroach sodium channel and examined the gating properties and Pyrethroid sensitivity of the three mutants in Xenopus oocytes. All three mutations reduced the channel sensitivity to three Pyrethroids (permethrin, cismethrin and deltamethrin). V409M, but not V409I or V409L, caused 6–7 mV depolarizing shifts in the voltage dependences of both activation and inactivation. V409M and V409L slowed channel activation kinetics and accelerated open-state deactivation kinetics, but V409I did not. Furthermore, the substitution of isoleucine with valine, but not with methionine nor leucine, at the corresponding position in a rat skeletal muscle sodium channel, rNa v 1.4, enhanced channel sensitivity to deltamethrin. Collectively, our study highlights an important role of residues at 409 in regulating not only sodium channel gating, but also the differential sensitivities of insect and mammalian sodium channels to Pyrethroids.
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a sodium channel mutation identified in aedes aegypti selectively reduces cockroach sodium channel sensitivity to type i but not type ii Pyrethroids
Insect Biochemistry and Molecular Biology, 2011Co-Authors: Yoshiko Nomura, Ke DongAbstract:Voltage-gated sodium channels are the primary target of Pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in Pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to Pyrethroids. Recently, several novel mutations were reported in sodium channel genes of Pyrethroid-resistant Aedes mosquito populations. One of the mutations is a phenylalanine (F) to cysteine (C) change in segment 6 of domain III (IIIS6) of the Aedes mosquito sodium channel. Curiously, a previous study showed that alanine substitution of this F did not alter the action of deltamethrin, a type II Pyrethroid, on a cockroach sodium channel. In this study, we changed this F to C in a Pyrethroid-sensitive cockroach sodium channel and examined mutant channel sensitivity to permethrin as well as five other type I or type II Pyrethroids in Xenopus oocytes. Interestingly, the F to C mutation drastically reduced channel sensitivity to three type I Pyrethroids, permethrin, NRDC 157 (a deltamethrin analogue lacking the α-cyano group) and bioresemthrin, but not to three type II Pyrethroids, cypermethrin, deltamethrin and cyhalothrin. These results confirm the involvement of the F to C mutation in permethrin resistance, and raise the possibility that rotation of type I and type II Pyrethroids might be considered in the control of insect pest populations where this particular mutation is present.
John Vontas - One of the best experts on this subject based on the ideXlab platform.
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a sensory appendage protein protects malaria vectors from Pyrethroids
Nature, 2020Co-Authors: Victoria A Ingham, Amalia Anthousi, Vassilis Douris, Nicholas J Harding, Gareth J Lycett, Marion Morris, John Vontas, Hilary RansonAbstract:Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to Pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers Pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with Pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to Pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to Pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts. The leg-enriched sensory appendage protein, SAP2, confers Pyrethroid resistance to Anopheles gambiae, through high-affinity binding of Pyrethroid insecticides; an observed selective sweep in field mosquitoes mirrors the increasing resistance reported in Africa.
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a sensory appendage protein protects malaria vectors from Pyrethroids
Nature, 2020Co-Authors: Victoria A Ingham, Amalia Anthousi, Vassilis Douris, Nicholas J Harding, Gareth J Lycett, Marion Morris, John Vontas, Hilary RansonAbstract:Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to Pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers Pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with Pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to Pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to Pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts.
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glutathione s transferases as antioxidant defence agents confer Pyrethroid resistance in nilaparvata lugens
Biochemical Journal, 2001Co-Authors: John Vontas, Graham J Small, Janet HemingwayAbstract:Selection of a laboratory colony of the brown planthopper Nilaparvata lugens with the Pyrethroids permethrin and lambda-cyhalothrin increased its resistance to both insecticides. Biochemical analysis and synergistic studies with metabolic inhibitors indicated that elevated glutathione S-transferases (GSTs) with a predominant peroxidase activity conferred resistance to both Pyrethroids, whereas esterases conferred part of the resistance to permethrin. Purified esterases hydrolysed permethrin at a slow rate, but incubation of either Pyrethroid or their primary metabolites with partially purified GSTs had no effect on the metabolic profile. Although GSTs were sensitive to inhibition by both Pyrethroids, they did not serve as binding proteins, as previously hypothesized [Grant and Matsumura (1988) Insect Biochem. 18, 615-622]. We demonstrate that Pyrethroids, in addition to their neurotoxic effect, induce oxidative stress and lipid peroxidation in insects. Pyrethroid exposure induced lipid peroxides, protein oxidation and depleted reduced glutathione. Elevated GSTs in the resistant strains attenuated the Pyrethroid-induced lipid peroxidation and reduced mortality, whereas their in vivo inhibition eliminated their protective role. We therefore hypothesize that the main role of elevated GSTs in conferring resistance in N. lugens is through protecting tissues from oxidative damage. Our study extends the GSTs' range of efficacy to Pyrethroid insecticides and possibly explains the role of elevated GSTs in other Pyrethroid-resistant insects.
Michael J. Devito - One of the best experts on this subject based on the ideXlab platform.
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Environmentally relevant Pyrethroid mixtures: A study on the correlation of blood and brain concentrations of a mixture of Pyrethroid insecticides to motor activity in the rat.
Toxicology, 2016Co-Authors: Michael F. Hughes, Edward J. Scollon, James M. Starr, David G Ross, Kevin M Crofton, Marcelo J Wolansky, Michael J. DevitoAbstract:Abstract Human exposure to multiple Pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to Pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of Pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the Pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis - and trans -permethrin in corn oil at seven dose levels. The Pyrethroid with the highest percentage in the dosing solution was trans -permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1 h. At 3.5 h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent Pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis -permethrin were the predominate Pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total Pyrethroid concentration between blood and brain was linear (r = 0.93). The Pyrethroids with the lowest fraction in blood were trans -permethrin and β-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed Pyrethroid blood and brain concentration was described using a sigmoidal E max model with the Effective Concentration 50 being more sensitive for brain than blood. The data suggests summed Pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of Pyrethroids administered as a mixture under the conditions used in this study.
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environmentally relevant mixtures in cumulative assessments an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of Pyrethroids
Toxicological Sciences, 2012Co-Authors: James M. Starr, Edward J. Scollon, Michael J. Devito, Michael F. Hughes, David G Ross, Stephen E Graham, Kevin M Crofton, Marcelo J WolanskyAbstract:Due to extensive use, human exposure to multiple Pyrethroid insecticides occurs frequently. Studies of Pyrethroid neurotoxicity suggest a common mode of toxicity and that Pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a Pyrethroid mixture that reflects human exposure to common Pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent Pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all Pyrethroids in all tissues were < 7h. Brain concentrations of all Pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between Pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal E(max) model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of Pyrethroid pesticides. The results support the additive model of Pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual Pyrethroids is related to toxicodynamic rather than toxicokinetic differences.
Hilary Ranson - One of the best experts on this subject based on the ideXlab platform.
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a sensory appendage protein protects malaria vectors from Pyrethroids
Nature, 2020Co-Authors: Victoria A Ingham, Amalia Anthousi, Vassilis Douris, Nicholas J Harding, Gareth J Lycett, Marion Morris, John Vontas, Hilary RansonAbstract:Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to Pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers Pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with Pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to Pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to Pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts.
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a sensory appendage protein protects malaria vectors from Pyrethroids
Nature, 2020Co-Authors: Victoria A Ingham, Amalia Anthousi, Vassilis Douris, Nicholas J Harding, Gareth J Lycett, Marion Morris, John Vontas, Hilary RansonAbstract:Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to Pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers Pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with Pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to Pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to Pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts. The leg-enriched sensory appendage protein, SAP2, confers Pyrethroid resistance to Anopheles gambiae, through high-affinity binding of Pyrethroid insecticides; an observed selective sweep in field mosquitoes mirrors the increasing resistance reported in Africa.
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the avecnet trial to assess whether addition of pyriproxyfen an insect juvenile hormone mimic to long lasting insecticidal mosquito nets provides additional protection against clinical malaria over current best practice in an area with Pyrethroid res
Trials, 2015Co-Authors: Alfred B Tiono, Margaret Pinder, Sagnon Nfale, Brian Faragher, Thomas J Smith, Mariabeth Silkey, Hilary Ranson, Steve W LindsayAbstract:Background Recent reductions in malaria in sub-Saharan Africa have been associated with increased coverage with long-lasting insecticidal nets (LLINs). Pyrethroids are currently the only insecticide class used for treating nets, and the rapid increase in resistance to Pyrethroids in vector mosquitoes may jeopardise future vector control. Nets containing a novel combination of permethrin, a Pyrethroid, and pyriproxyfen, an insect juvenile hormone mimic, (PPF-LLIN) may enhance malaria control, as well as reducing the spread of Pyrethroid-resistant mosquitoes. This trial will determine whether PPF-LLINs provide incremental protection against malaria over current best practice of LLINs and prompt treatment in an area with Pyrethroid-resistant vectors.
