Metabolism of imidacloprid and DDT by P450 CYP6G1 expressed in cell cultures of Nicotiana tabacum suggests detoxification of these insecticides in Cyp6g1‐overexpressing strains of Drosophila melanogaster, leading to resistance

Joußen, Nicole; Heckel, David G.; Haas, Matthias; Schuphan, Ingolf; Schmidt, Burkhard

doi:10.1002/ps.1472

Cited by 168 publications

(150 citation statements)

References 39 publications

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“…In only one previous instance has a single P450 been linked to resistance to more than one insecticidal compound. The Drosophila melanogaster P450, CYP6g1, is associated with resistance to neonicotinoids, the organophosphate malathion and organochlorines DDT and methoxychlor (35)(36)(37)(38). Cross-resistance is arguably an unexpectedly infrequent observation, given the broad substrate specificity of P450s to, for example, plant toxins (39,40).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a gene causing cross-resistance between insecticide classes inAnopheles gambiaefrom Ghana

Mitchell

Stevenson

Müller

et al. 2012

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

228

255

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In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a unique whole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a gene causing cross-resistance between insecticide classes inAnopheles gambiaefrom Ghana

Mitchell

Stevenson

Müller

et al. 2012

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

228

255

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“…Similarly, when the genetic switch UAS:GAL4 was used to overexpress different P450s in genetically transformed Drosophila (Daborn et al 2007), other P450s could again confer resistance to DDT (e.g., CYP12D1) but, critically, none of these other P450s has been shown to be correlated with resistance in field-collected strains. Finally, to prove that CYP6G1 can actually metabolize DDT, the enzyme has been expressed in a heterolgous expression system and has been shown to convert DDT to DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane) via dechlorination (Joussen et al 2008).…”

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confidence: 99%

The Molecular Genetics of Insecticide Resistance

2013

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The past 60 years have seen a revolution in our understanding of the molecular genetics of insecticide resistance. While at first the field was split by arguments about the relative importance of mono-vs. polygenic resistance and field-vs. laboratory-based selection, the application of molecular cloning to insecticide targets and to the metabolic enzymes that degrade insecticides before they reach those targets has brought out an exponential growth in our understanding of the mutations involved. Molecular analysis has confirmed the relative importance of single major genes in target-site resistance and has also revealed some interesting surprises about the multi-gene families, such as cytochrome P450s, involved in metabolic resistance. Identification of the mutations involved in resistance has also led to parallel advances in our understanding of the enzymes and receptors involved, often with implications for the role of these receptors in humans. This Review seeks to provide an historical perspective on the impact of molecular biology on our understanding of resistance and to begin to look forward to the likely impact of rapid advances in both sequencing and genome-wide association analysis."Curiouser and curiouser!" cried Alice.Lewis Carroll L ewis Carroll sent Alice down a rabbit hole without the least idea of what was to happen next, but as Alice ventured deeper into Wonderland things became "Curiouser and curiouser!" So indeed have studies on the molecular basis of insecticide resistance. While starting with rather simplistic expectations about the role of single mutations in single genes, resistance has been shown to involve a panoply of multiple mutations in multiple genes, often with independent and complex origins. This review will attempt to place these current findings into context and to examine the extent to which the field has often been historically blindsided by dogma. My arguments will encompass key controversies debated in the field such as the relative importance of mono-vs. polygenic resistance and the implications of resistance-associated mutations for whole-organism fitness in the absence of pesticide. Importantly, we will also examine the role of dogma in shaping the way that resistance research has been pursued over the past 50 years. Key questions addressed are therefore: How many mutations per gene cause resistance? How many mechanisms are there per species (genome)? How many independent genetic origins (mutations) give rise to each mechanism? What new mechanisms are still undiscovered and how might they arise? Monogenic vs. Polygenic ResistanceCrow, DDT, and DrosophilaThe humble fruit fly Drosophila melanogaster has been a key tool in unlocking the molecular basis of insecticide resistance, and early studies by James Crow and others have helped to establish Drosophila as a genetic model for resistance studies. Studies of DDT resistance in Drosophila have also typified arguments surrounding mono-vs. polygenic inheritance of insecticide resistance. In his pioneering review of in...

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“…However, it has been shown that TE insertions in the proximity of Cyps can alter their regulation and cause the over-expression of CYP enzymes, resulting in insecticide resistance (Catania et al, 2004;Daborn et al, 2001Daborn et al, , 2002Jouben et al, 2008). TE insertions could therefore also be a source of genetic variability, and the regulatory motifs they provide could be advantageous for organisms in responding to external stimuli.…”

Section: Discussionmentioning

confidence: 99%

Genomic regions harboring insecticide resistance-associated Cyp genes are enriched by transposable element fragments carrying putative transcription factor binding sites in two sibling Drosophila species

Carareto

Hernandez

Vieira

2014

Gene

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a b s t r a c tIn the present study, an in silico analysis was performed to identify transposable element (TE) fragments inserted in Cyps with functions associated with resistance to insecticides and developmental regulation as well as in neighboring genes in two sibling species , Drosophila melanogaster and Drosophila simulans . The Cyps associated with insecticide resistance and their neighboring non-Cyp genes have accumulated a greater number of TE fragments than the other Cyps or a random sample of genes, predominantly in the 5′-flanking regions. Most of the insertions were due to DNA transposons, with DNAREP1 fragments being the most common. These fragments carry putative binding sites for transcription factors, which reinforces the hypothesis that DNAREP1 may influence gene regulation and play a role in the adaptation of the Drosophila species.

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Metabolism of imidacloprid and DDT by P450 CYP6G1 expressed in cell cultures of Nicotiana tabacum suggests detoxification of these insecticides in Cyp6g1‐overexpressing strains of Drosophila melanogaster, leading to resistance

Abstract: Thus, the gap between the supposed resistance gene Cyp6g1 and the observed resistance phenomenon was closed by the evidence that CYP6G1 is capable of metabolising at least two insecticides.

Cited by 168 publications

References 39 publications

Identification and validation of a gene causing cross-resistance between insecticide classes inAnopheles gambiaefrom Ghana

Identification and validation of a gene causing cross-resistance between insecticide classes inAnopheles gambiaefrom Ghana

The Molecular Genetics of Insecticide Resistance

Genomic regions harboring insecticide resistance-associated Cyp genes are enriched by transposable element fragments carrying putative transcription factor binding sites in two sibling Drosophila species

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