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Charles S. Wondji - One of the best experts on this subject based on the ideXlab platform.

  • investigating Knockdown Resistance kdr mechanism against pyrethroids ddt in the malaria vector anopheles funestus across africa
    BMC Genetics, 2017
    Co-Authors: Helen Irving, Charles S. Wondji
    Abstract:

    Understanding the molecular basis of insecticide Resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the Knockdown Resistance (kdr) mechanism. Here, we investigated the presence and contribution of Knockdown Resistance (kdr) to pyrethroids/DDT Resistance observed in Anopheles funestus across Africa. Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An. funestus across Africa. Amplification and cloning of the full-length of the sodium channel gene in pyrethroid resistant mosquitoes revealed evidences of alternative splicing events with three transcripts of 2092, 2061 and 2117 amino acids (93% average similarity to An. gambiae). Several amino acid changes were detected close to the domain II of the protein such as L928R, F938 W, I939S, L802S and T1008 M. However, all these mutations are found at low frequency and their role in pyrethroid Resistance could not be established. The presence of the exclusive alternative splicing at exon 19 was not associated with Resistance phenotype. Analysis of patterns of genetic diversity of the VGSC gene revealed a high polymorphism level of this gene across Africa with no evidence of directional selection suggesting a limited role for Knockdown Resistance in pyrethroid Resistance in An. funestus. Patterns of genetic differentiation correlate with previous observations of the existence of barriers to gene flow Africa-wide with southern population significantly differentiated from other regions. Despite an apparent limited role of Knockdown Resistance in An. funestus, it is necessary to continue to monitor the contribution of the mutations detected here as increasing selection from insecticide-based interventions may change the dynamic in field populations as previously observed in other vectors.

  • Investigating Knockdown Resistance (kdr) mechanism against pyrethroids/DDT in the malaria vector Anopheles funestus across Africa.
    BMC Genetics, 2017
    Co-Authors: Helen Irving, Charles S. Wondji
    Abstract:

    Understanding the molecular basis of insecticide Resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the Knockdown Resistance (kdr) mechanism. Here, we investigated the presence and contribution of Knockdown Resistance (kdr) to pyrethroids/DDT Resistance observed in Anopheles funestus across Africa. Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An. funestus across Africa. Amplification and cloning of the full-length of the sodium channel gene in pyrethroid resistant mosquitoes revealed evidences of alternative splicing events with three transcripts of 2092, 2061 and 2117 amino acids (93% average similarity to An. gambiae). Several amino acid changes were detected close to the domain II of the protein such as L928R, F938 W, I939S, L802S and T1008 M. However, all these mutations are found at low frequency and their role in pyrethroid Resistance could not be established. The presence of the exclusive alternative splicing at exon 19 was not associated with Resistance phenotype. Analysis of patterns of genetic diversity of the VGSC gene revealed a high polymorphism level of this gene across Africa with no evidence of directional selection suggesting a limited role for Knockdown Resistance in pyrethroid Resistance in An. funestus. Patterns of genetic differentiation correlate with previous observations of the existence of barriers to gene flow Africa-wide with southern population significantly differentiated from other regions. Despite an apparent limited role of Knockdown Resistance in An. funestus, it is necessary to continue to monitor the contribution of the mutations detected here as increasing selection from insecticide-based interventions may change the dynamic in field populations as previously observed in other vectors.

  • The cytochrome P450 CYP6P4 is responsible for the high pyrethroid Resistance in Knockdown Resistance-free Anopheles arabiensis.
    Insect biochemistry and molecular biology, 2015
    Co-Authors: Sulaiman S. Ibrahim, Helen Irving, Jacob M. Riveron, Robert Stott, Charles S. Wondji
    Abstract:

    Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, Resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid Resistance in a Knockdown Resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid Resistance (rp1) quantitative trait locus (QTL), is responsible for Resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field Resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid Resistance gene explained the observed field Resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in Resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of Resistance before implementing Resistance management/control tools.

  • contrasting patterns of insecticide Resistance and Knockdown Resistance kdr in the dengue vectors aedes aegypti and aedes albopictus from malaysia
    Parasites & Vectors, 2015
    Co-Authors: Intan H Ishak, Hilary Ranson, Zairi Jaal, Charles S. Wondji
    Abstract:

    Knowledge on the extent, distribution and mechanisms of insecticide Resistance is essential for successful insecticide-based dengue control interventions. Here, we report an extensive Resistance profiling of the dengue vectors Aedes aegypti and Aedes albopictus across Malaysia and establish the contribution of Knockdown Resistance mechanism revealing significant contrast between both species. Aedes mosquitoes were collected from four states in Malaysia in 2010 using ovitraps and tested against six major insecticides using WHO bioassays. Knockdown Resistance (kdr) was investigated in both species. A moderate Resistance to temephos was detected from samples collected in 2010 in Penang, Kuala Lumpur, Johor Bharu and Kota Bharu (1.5 < RR < 3.3). A widespread and multiple Resistances was observed in Ae. aegypti particularly against pyrethroids, DDT and bendiocarb. Mosquitoes from Kuala Lumpur consistently had the highest Resistance levels and was the only population showing a moderate Resistance to malathion (91% mortality). The Resistance profile of Ae. albopictus contrasted to Ae. aegypti with full susceptibility to pyrethroids except in Kuala Lumpur where moderate Resistance is observed. PBO synergist assays suggest metabolic Resistance mechanisms play a major role in Resistance in both species. Two kdr mutations, F1534C and V1016G, were detected in Ae. aegypti across Malaysia but neither of these mutations were found in Ae. albopictus. Additionally, signatures of selection were detected on the Voltage-gated sodium channel gene in Ae. aegypti but not in Ae. albopictus. The presence of the 1534C allele was significantly associated with pyrethroid Resistance and an additive effect to pyrethroid Resistance was observed in individuals containing both kdr alleles. Findings from this study will help to design and implement successful insecticide-based interventions against Ae. aegypti and Ae. albopictus to improve dengue control across Malaysia.

  • Characterization of Knockdown Resistance in DDT- and pyrethroid-resistant Culex quinquefasciatus populations from Sri Lanka
    Tropical medicine & international health : TM & IH, 2008
    Co-Authors: Charles S. Wondji, Hilary Ranson, W. A. Priyanka P. De Silva, Janet Hemingway, S. H. P. Parakrama Karunaratne
    Abstract:

    DDT and pyrethroid Resistance in Culex quinquefasciatus have been previously reported in Sri Lanka, but the mechanisms involved have yet to be characterized. We report the presence of two mutant alleles of the sodium channel gene, the target site for both DDT and pyrethroid insecticides. Both mutations resulted in classic Knockdown Resistance (kdr) L1014F mutation because of either an A-to-T substitution or an A-to-C substitution. We developed two alternative assays to distinguish between the two mutations and used these to screen 214 individuals from nine geographic locations throughout Sri Lanka. Very high levels of kdr mutations were found throughout the country. A predominance of the A-to-C mutation was observed over the A-to-T with an average allele frequency of 50% and 2%, respectively. In addition to these non-synonymous kdr substitutions, we also found an indel (TCACA) in the intron downstream of the kdr mutation. After genotyping this indel in 136 individuals, we found no evident correlation between kdr genotypes and intronic indel. The presence of two alternative kdr mutations has implications for the reliance on single molecular diagnostics for detection of Resistance in field populations. Furthermore, the high levels of these kdr mutations in C. quinquefasciatus populations throughout Sri Lanka are of concern for the future of pyrethroid-based control programmes on this island.

Martin S. Williamson - One of the best experts on this subject based on the ideXlab platform.

  • detection of Knockdown Resistance kdr mutations in anopheles gambiae a comparison of two new high throughput assays with existing methods
    Malaria Journal, 2007
    Co-Authors: Chris Bass, Martin S. Williamson, Dimitra Nikou, Martin J Donnelly, Hilary Ranson, Amanda Ball, John Vontas, Linda M Field
    Abstract:

    Background Knockdown Resistance (kdr) is a well-characterized mechanism of Resistance to pyrethroid insecticides in many insect species and is caused by point mutations of the pyrethroid target site the para-type sodium channel. The presence of kdr mutations in Anopheles gambiae, the most important malaria vector in Africa, has been monitored using a variety of molecular techniques. However, there are few reports comparing the performance of these different assays. In this study, two new high-throughput assays were developed and compared with four established techniques.

  • High-throughput detection of Knockdown Resistance in Myzus persicae using allelic discriminating quantitative PCR.
    Insect biochemistry and molecular biology, 2004
    Co-Authors: James A. Anstead, Martin S. Williamson, Ioannis Eleftherianos, Ian Denholm
    Abstract:

    Abstract The peach–potato aphid Myzus persicae (Sulzer) has developed Resistance to pyrethroid insecticides as a result of a mechanism conferring reduced nervous system sensitivity, termed Knockdown Resistance (kdr). This reduced sensitivity is caused by two mutations, L1014F (kdr) and M918T (super-kdr), in the para-type voltage-gated sodium channel. We have developed a diagnostic dose bioassay to detect kdr and provide preliminary information on the genotype present. We also developed two allelic discrimination PCR assays to determine precisely the genotypes of the two mutations (L1014F and M918T) in individual M. persicae using fluorescent Taqman ® MGB probes. In combination with assays for elevated carboxylesterase levels and modified acetylcholinesterase (MACE), this suite of assays allows for rapid high-throughput diagnosis, in individual aphids, of the three main Resistance mechanisms of practical importance in the UK.

  • Toxicological and molecular characterisation of pyrethroid Knockdown Resistance (kdr) in the peach-potato aphids, Myzus persicae (sulzer)
    2001
    Co-Authors: Ioannis Eleftherianos, Stephen P. Foster, Martin S. Williamson, Ian Denholm
    Abstract:

    Eleftherianos I., Foster S., Williamson M., Denholm A., (2003), Toxicological and molecular characterisation of pyrethroid Knockdown Resistance (kdr) in the peach-potato aphids, Myzus persicae (sulzer), Paper presented at the 6th International Symposium on Aphids Conference, Rennes, France, September, 2003, ISBN 978-2-7380-1113-8, published by Ecole Nationale Superieure Agronomique de Rennes (ENSAR)

  • Toxicological, Electrophysiological, and Molecular Characterisation of Knockdown Resistance to Pyrethroid Insecticides in the Diamondback Moth,Plutella xylostella(L.)
    Pesticide Biochemistry and Physiology, 1998
    Co-Authors: T. H. Schuler, Ian Denholm, Alan L Devonshire, David Martínez-torres, Andrew J. Thompson, Ian R. Duce, Martin S. Williamson
    Abstract:

    Abstract Nerve insensitivity was shown to be a major cause of high pyrethroid Resistance in a Taiwanese strain of the diamondback moth,Plutella xylostella. Initial evidence for this type of target site insensitivity, also termed Knockdown Resistance orkdr, was provided by nonsynergizable cross-Resistance to a range of pyrethroids and DDT and an incompletely recessive autosomal inheritance of the Resistance trait. This was corroborated by using a larval neuromuscular preparation to assess spontaneous miniature excitatory postsynaptic potentials (mEPSPs) and evoked EPSPs in response to varying concentrations of the pyrethroid deltamethrin. Intracellular recordings revealed a pyrethroid-induced increase in mEPSP activity and a decline in the EPSP amplitude; responses were induced only at considerably higher concentrations in resistant larvae when compared to larvae of a susceptible standard strain. These findings were supported by the detection of two amino acid changes in part of thepara-type voltage-sensitive sodium channel (the primary target site of pyrethroids) of the resistant strain. One of these mutations, a leucine to phenylalanine replacement in transmembrane segment 6 of domain II, has previously been shown to correlate withkdrin the house fly,Musca domestica, and German cockroach,Blattella germanica.

  • molecular studies of Knockdown Resistance to pyrethroids cloning of domain ii sodium channel gene sequences from insects
    Pesticide Science, 1997
    Co-Authors: David Martineztorres, A L Devonshire, Martin S. Williamson
    Abstract:

    Knockdown Resistance (kdr) is a target-site Resistance mechanism that confers nerve insensitivity to DDT and pyrethroid insecticides. In the housefly, Musca domestica, molecular cloning of the para-type sodium channel gene has revealed two amino acid mutations that are associated with kdr and super-kdr Resistance phenotypes. Both mutations are located in the domain II region of the channel; Leu1014 to Phe in the hydrophobic segment IIS6 and Met918 to Thr in the IIS4-IIS5 linker. To investigate whether these mutations also occur in other insects, we have designed degenerate primers based on conserved sequences in the domain II region of the sodium channel and used these to PCR amplify this region from insecticide-susceptible strains of eight diverse insect species representing four different insect Orders: Helicoverpa armigera, Plutella xylostella, Spodoptera littoralis (Lepidoptera), Blattella germanica (Dictyoptera), Tribolium castaneum (Coleoptera), Myzus persicae, Aphis gossypii and Phorodon humuli (Hemiptera). The primers amplified closely related para-type sodium channel sequences from each insect with a minimum of 85% amino acid identity between species. All of the sequences contained 'susceptible' Leu and Met residues at the positions associated with kdr and super-kdr Resistance in the housefly. Recent results detailing the presence of a kdr-type Leu to Phe mutation in pyrethroid-resistant strains of two important agricultural pests, P. xylostella and M. persicae, are discussed.

João Pinto - One of the best experts on this subject based on the ideXlab platform.

  • Polymorphism of intron-1 in the voltage-gated sodium channel gene of Anopheles gambiae s.s. populations from Cameroon with emphasis on insecticide Knockdown Resistance mutations.
    Molecular ecology, 2009
    Co-Authors: Josiane Etang, José L. Vicente, Frédéric Simard, Virgílio E. Do Rosário, Philippe Nwane, Mouhamadou Chouaibou, Isabelle Morlais, Parfait Awono-ambene, Jean Claude Toto, João Pinto
    Abstract:

    Sequence variation at the intron-1 of the voltage-gated sodium channel gene in Anopheles gambiae M- and S-forms from Cameroon was assessed to explore the number of mutational events originating Knockdown Resistance (kdr) alleles. Mosquitoes were sampled between December 2005 and June 2006 from three geographical areas: (i) Magba in the western region; (ii) Loum, Tiko, Douala, Kribi, and Campo along the Atlantic coast; and (iii) Bertoua, in the eastern continental plateau. Both 1014S and 1014F kdr alleles were found in the S-form with overall frequencies of 14% and 42% respectively. Only the 1014F allele was found in the M-form at lower frequency (11%). Analysis of a 455 bp region of intron-1 upstream the kdr locus revealed four independent mutation events originating kdr alleles, here named MS1 -1014F, S1-1014S and S2-1014S kdr-intron-1 haplotypes in S-form and MS3-1014F kdr-intron-1 haplotype in the M-form. Furthermore, there was evidence for mutual introgression of kdr 1014F allele between the two molecular forms, MS1 and MS3 being widely shared by them. Although no M/S hybrid was observed in analysed samples, this wide distribution of haplotypes MS1 and MS3 suggests inter-form hybridizing at significant level and emphasizes the rapid diffusion of the kdr alleles in Africa. The mosaic of genetic events found in Cameroon is representative of the situation in the West–Central African region and highlights the importance of evaluating the spatial and temporal evolution of kdr alleles for a better management of insecticide Resistance.

  • A primer-introduced restriction analysis-polymerase chain reaction method to detect Knockdown Resistance mutations in Anopheles gambiae.
    Journal of medical entomology, 2008
    Co-Authors: F. Janeira, José L. Vicente, Marta Moreno, Y. Kanganje, V. E. Do Rosario, Pedro Cravo, João Pinto
    Abstract:

    In the major malaria vector Anopheles gambiae Giles, two point mutations at the voltage-gated sodium channel have been associated with Knockdown Resistance (kdr) to DDT and pyrethroid insecticides. Simple allele-specific polymerase chain reaction (PCR) assays to detect these single-nucleotide polymorphisms are prone to lack of specificity and therefore alternative techniques have been proposed. However, these may not be easily implemented in many laboratories from malaria endemic regions. Here, we describe a primer-introduced restriction analysis (PIRA)-PCR method to detect kdr mutations in An. gambiae. This method unambiguously identified all six genotypes for the kdr locus in a sample of 113 field-collected mosquitoes for which kdr genotypes had been confirmed by DNA sequencing. Co-occurrence of both kdr alleles was found in sites from Equatorial Guinea and Gabon and the L1014F mutation was detected in M-form individuals from Angola. The PIRA-PCR proved to be a reliable, robust, and simpler alternative for the detection of kdr mutations in this malaria vector.

  • Multiple origins of Knockdown Resistance mutations in the Afrotropical mosquito vector Anopheles gambiae.
    PloS one, 2007
    Co-Authors: João Pinto, Amy Lynd, José L. Vicente, Federica Santolamazza, Nadine Randle, Gabriele Gentile, Marta Moreno, Frédéric Simard, J. D. Charlwood, Virgílio E. Do Rosário
    Abstract:

    How often insecticide Resistance mutations arise in natural insect populations is a fundamental question for understanding the evolution of Resistance and also for modeling its spread. Moreover, the development of Resistance is regarded as a favored model to study the molecular evolution of adaptive traits. In the malaria vector Anopheles gambiae two point mutations (L1014F and L1014S) in the voltage-gated sodium channel gene, that confer Knockdown Resistance (kdr) to DDT and pyrethroid insecticides, have been described. In order to determine whether Resistance alleles result from single or multiple mutation events, genotyping of the kdr locus and partial sequencing of the upstream intron-1 was performed on a total of 288 A. gambiae S-form collected from 28 localities in 15 countries. Knockdown Resistance alleles were found to be widespread in West Africa with co-occurrence of both 1014S and 1014F in West-Central localities. Differences in intron-1 haplotype composition suggest that kdr alleles may have arisen from at least four independent mutation events. Neutrality tests provided evidence for a selective sweep acting on this genomic region, particularly in West Africa. The frequency and distribution of these kdr haplotypes varied geographically, being influenced by an interplay between different mutational occurrences, gene flow and local selection. This has important practical implications for the management and sustainability of malaria vector control programs.

Alan L Devonshire - One of the best experts on this subject based on the ideXlab platform.

  • Toxicological, Electrophysiological, and Molecular Characterisation of Knockdown Resistance to Pyrethroid Insecticides in the Diamondback Moth,Plutella xylostella(L.)
    Pesticide Biochemistry and Physiology, 1998
    Co-Authors: T. H. Schuler, Ian Denholm, Alan L Devonshire, David Martínez-torres, Andrew J. Thompson, Ian R. Duce, Martin S. Williamson
    Abstract:

    Abstract Nerve insensitivity was shown to be a major cause of high pyrethroid Resistance in a Taiwanese strain of the diamondback moth,Plutella xylostella. Initial evidence for this type of target site insensitivity, also termed Knockdown Resistance orkdr, was provided by nonsynergizable cross-Resistance to a range of pyrethroids and DDT and an incompletely recessive autosomal inheritance of the Resistance trait. This was corroborated by using a larval neuromuscular preparation to assess spontaneous miniature excitatory postsynaptic potentials (mEPSPs) and evoked EPSPs in response to varying concentrations of the pyrethroid deltamethrin. Intracellular recordings revealed a pyrethroid-induced increase in mEPSP activity and a decline in the EPSP amplitude; responses were induced only at considerably higher concentrations in resistant larvae when compared to larvae of a susceptible standard strain. These findings were supported by the detection of two amino acid changes in part of thepara-type voltage-sensitive sodium channel (the primary target site of pyrethroids) of the resistant strain. One of these mutations, a leucine to phenylalanine replacement in transmembrane segment 6 of domain II, has previously been shown to correlate withkdrin the house fly,Musca domestica, and German cockroach,Blattella germanica.

  • identification of mutations in the housefly para type sodium channel gene associated with Knockdown Resistance kdr to pyrethroid insecticides
    Molecular Genetics and Genomics, 1996
    Co-Authors: Martin S. Williamson, David Martineztorres, Caroline A. Hick, Alan L Devonshire
    Abstract:

    We report the isolation of cDNA clones containing the full 6.3-kb coding sequence of thepara-type sodium channel gene of the housefly,Musca domestica. This gene has been implicated as the site of Knockdown Resistance (kdr), an important Resistance mechanism that confers nerve insensitivity to DDT and pyrethroid insecticides. The cDNAs predict a polypeptide of 2108 amino acids with close sequence homology (92% identity) to theDrosophila para sodium channel, and around 50% homology to vertebrate sodium channels. Only one major splice form of the housefly sodium channel was detected, in contrast to theDrosophila para transcript which has been reported to undergo extensive alternative splicing. Comparative sequence analysis of housefly strains carryingkdr or the more potentsuper-kdr factor revealed two amino acid mutations that correlate with these Resistance phenotypes. Both mutations are located in domain II of the sodium channel. A leucine to phenylalanine replacement in the hydrophobic IIS6 transmembrane segment was found in two independentkdr strains and sixsuper-kdr strains of diverse geographic origin, while an additional methionine to threonine replacement within the intracellular IIS4-S5 loop was found only in thesuper-kdr strains. Neither mutation was present in five pyrethroid-sensitive strains. The mutations suggest a binding site for pyrethroids at the intracellular mouth of the channel pore in a region known to be important for channel inactivation.

  • Identification of mutations in the houseflypara-type sodium channel gene associated with Knockdown Resistance (kdr) to pyrethroid insecticides
    Molecular and General Genetics MGG, 1996
    Co-Authors: Martin S. Williamson, David Martínez-torres, Caroline A. Hick, Alan L Devonshire
    Abstract:

    We report the isolation of cDNA clones containing the full 6.3-kb coding sequence of the para -type sodium channel gene of the housefly, Musca domestica . This gene has been implicated as the site of Knockdown Resistance ( kdr ), an important Resistance mechanism that confers nerve insensitivity to DDT and pyrethroid insecticides. The cDNAs predict a polypeptide of 2108 amino acids with close sequence homology (92% identity) to the Drosophila para sodium channel, and around 50% homology to vertebrate sodium channels. Only one major splice form of the housefly sodium channel was detected, in contrast to the Drosophila para transcript which has been reported to undergo extensive alternative splicing. Comparative sequence analysis of housefly strains carrying kdr or the more potent super-kdr factor revealed two amino acid mutations that correlate with these Resistance phenotypes. Both mutations are located in domain II of the sodium channel. A leucine to phenylalanine replacement in the hydrophobic IIS6 transmembrane segment was found in two independent kdr strains and six super-kdr strains of diverse geographic origin, while an additional methionine to threonine replacement within the intracellular IIS4-S5 loop was found only in the super-kdr strains. Neither mutation was present in five pyrethroid-sensitive strains. The mutations suggest a binding site for pyrethroids at the intracellular mouth of the channel pore in a region known to be important for channel inactivation.

  • Knockdown Resistance kdr to ddt and pyrethroid insecticides maps to a sodium channel gene locus in the housefly musca domestica
    Molecular Genetics and Genomics, 1993
    Co-Authors: Martin S. Williamson, Ian Denholm, Caroline A Bell, Alan L Devonshire
    Abstract:

    The voltage-sensitive sodium channel is generally regarded as the primary target site of dichlorodiphenyl-trichloro-ethane (DDT) and pyrethroid insecticides, and has been implicated in the widely reported mechanism of nerve insensitivity to these compounds. This phenomenon is expressed as Knockdown Resistance (kdr) and has been best characterised in the housefly where several putative alleles, including the more potent super-kdr factor, have been identified. We report the isolation of cDNA clones containing part of a housefly sodium channel gene, designated Msc, which show close homology to the para sodium channel of Drosophila (99% amino acid identity within the region of overlap). Using Southern blots of insect DNA, restriction fragment length polymorphisms (RFLPs) at the Msc locus were identified in susceptible, kdr and super-kdr housefly strains. These RFLPs showed tight linkage to Resistance in controlled crosses involving these strains, thus providing clear genetic evidence that kdr, and hence pyrethroid mode of action, is closely associated with the voltage-sensitive sodium channel.

Pradya Somboon - One of the best experts on this subject based on the ideXlab platform.