Why are there so few resistance–associated mutations in insecticide target genes?

ffrench-Constant, Richard H.; Pittendrigh, Barry R.; Vaughan, Ashley M.; Anthony, Nicola M.

doi:10.1098/rstb.1998.0319

Cited by 121 publications

(65 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results are generally comparable with observations of the effects of dieldrin and fipronil on resistant RDL subunit of Drosophila (Wolff and Wingate, 1998). When mutated, RDL-containing GABA receptor acquire resistance to picrotoxinin and dieldrin (Hosie et al, 1997;ffrench-Constant et al, 1998). Resistance to fipronil in these cases is variable compared with susceptible counterparts, whereas a low resistance ratio to fipronil was reported in sensitive and resistant strains of Blatella germanica (for review see Bloomquist, 2001).…”

Section: Discussionsupporting

confidence: 78%

Differential sensitivity of two insect GABA-gated chloride channels to dieldrin, fipronil and picrotoxinin

Corronc

Alix

Hue

2002

Journal of Insect Physiology

View full text Add to dashboard Cite

In the central nervous system of both vertebrates and invertebrates inhibitory neurotransmission is mainly achieved through activation of γ-aminobutyric acid (GABA) receptors. Extensive studies have established the structural and pharmacological properties of vertebrate GABA receptors. Although the vast majority of insect GABA-sensitive responses share some properties with vertebrate GABAA receptors, peculiar pharmacological properties of these receptors led us to think that several GABA-gated chloride channels are present in insects. We describe here the pharmacological properties of two GABA receptor subtypes coupled to a chloride channel on dorsal unpaired median (DUM) neurones of the adult male cockroach. Long applications of GABA induce a large biphasic hyperpolarization, consisting of an initial transient hyperpolarization followed by a slow phase of hyperpolarization that is not quickly desensitized. With GABA, the transient hyperpolarization is sensitive to picrotoxinin, fipronil and dieldrin whereas the slow response is insensitive to these insecticides.When GABA is replaced by muscimol and cis-4-aminocrotonic acid (CACA) a biphasic hyperpolarization consisting of an initial transient hyperpolarization followed by a sustained phase is evoked which is blocked by picrotoxinin and fipronil. Exposure to dieldrin decreases only the early phase of the muscimol and CACA-induced biphasic response, suggesting that two GABA-gated chloride channel receptor subtypes are present in DUM neurones. This study describes, for the first time, a dieldrin resistant component different to the dieldrin-and picrotoxinin-resistant receptor found in several insect species. 

show abstract

Section: Discussionsupporting

confidence: 78%

Differential sensitivity of two insect GABA-gated chloride channels to dieldrin, fipronil and picrotoxinin

Corronc

Alix

Hue

2002

Journal of Insect Physiology

View full text Add to dashboard Cite

show abstract

“…Thus, the Ala 301 to Ser or Gly mutation in Rdl exhibits unique properties, providing high levels of dieldrin resistance without abolishing the role of the RDL receptor (12). Electrophysiological studies showed that the 301 replacement affects cyclodiene sensitivity by two mechanisms: inhibiting direct binding and allosterically modifying the Rdl receptor to disrupt the antagonist-favored conformation (13).…”

mentioning

confidence: 99%

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

Remnant

Good

Schmidt

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized in Drosophila melanogaster by genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala 301 to Ser. The equivalent change was subsequently identified in Rdl orthologs of a large range of resistant insect species. Here, we report identification of a duplication at the Rdl locus in D. melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second copy with two point mutations: an Ala 301 to Ser resistance mutation and Met 360 to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser 301 homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination between Roo transposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kb Rdl locus with a Ser 301 change into an Ala 301 background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of the Rdl target site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene.T he single point mutation in the Resistance to dieldrin (Rdl) gene represents one of the most significant cases of target site resistance to an insecticide yet observed. Cyclodiene resistance was reported in 62% of insecticide resistant species in the 1980s, following widespread use of cyclodiene insecticides, including dieldrin, which started in the 1950s (1). The nature of the genetic target, Rdl, was discovered after dieldrin was discontinued because of the widespread evolution of resistance in many species. Rdl was first discovered in Drosophila melanogaster using a positional cloning approach. High homology to human GABA receptors confirmed it was the first insect ligand-gated chloride channel subunit identified (2-4). A point mutation in the chloride channel pore-lining domain, replacing alanine 301 with serine, was present in all resistant D. melanogaster strains (5). This mutation provided 4,000-fold resistance when homozygous and lower levels of resistance in heterozygotes (2, 6). The homologous mutation was subsequently found in a large number of cyclodiene-resistant species from many insect orders (7-9), as well as a glycine replacement at the homologous site in some resistant strains of Drosophila simulans and other species (5, 10, 11).Characterization of deficiency lines and inversions in D. melanogaster showed that Rdl is an essential gene (3). Thus, the Ala 301 to Ser or Gly mutation in Rdl exhibits unique properties, p...

show abstract

“…Insecticide resistance has been reported from many insects including A. gambiae that showed the presence of insensitive acetylcholinesterase in two different populations that were resistant to carbosulfan, a carbamate insecticide (N'Guessan et al, 2003). Mutations at a single codon in the Rdl (resistance to dieldrin) gene have been documented in all dieldrinresistant insects, and confer both insensitivity to the insecticide and a decrease rate of desensitisation (ffrench-Constant et al, 1998). However, in A. gambiae this type of resistance mechanism has not been described so far.…”

Section: Target Site Resistancementioning

confidence: 99%

The Role of Anopheles gambiae P450 Cytochrome in Insecticide Resistance and Infection

Félix¹,

Silveira²

2012

Insecticides - Pest Engineering

View full text Add to dashboard Cite

Why are there so few resistance–associated mutations in insecticide target genes?

Cited by 121 publications

References 60 publications

Differential sensitivity of two insect GABA-gated chloride channels to dieldrin, fipronil and picrotoxinin

Differential sensitivity of two insect GABA-gated chloride channels to dieldrin, fipronil and picrotoxinin

Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster

The Role of Anopheles gambiae P450 Cytochrome in Insecticide Resistance and Infection

Contact Info

Product

Resources

About