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‘What I cannot create, I do not understand’: functionally validated synergism of metabolic and target site insecticide resistance.

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Title: ‘What I cannot create, I do not understand’: functionally validated synergism of metabolic and target site insecticide resistance.
Authors: Samantsidis, George-Rafael1,2, Panteleri, Rafaela1,2, Denecke, Shane1, Kounadi, Stella1,2, Christou, Iason1,2, Nauen, Ralf3, Douris, Vassilis1,4, Vontas, John1,5 vontas@imbb.forth.gr
Source: Proceedings of the Royal Society B: Biological Sciences. 5/27/2020, Vol. 287 Issue 1927, p1-10. 10p.
Subjects: Insecticide resistance, Aedes aegypti, Genetic transformation, Sodium channels, CRISPRs, Malaria
Abstract: The putative synergistic action of target-site mutations and enhanced detoxification in pyrethroid resistance in insects has been hypothesized as a major evolutionary mechanism responsible for dramatic consequences in malaria incidence and crop production. Combining genetic transformation and CRISPR/Cas9 genome modification, we generated transgenic Drosophila lines expressing pyrethroid metabolizing P450 enzymes in a genetic background along with engineered mutations in the voltage-gated sodium channel (para) known to confer target-site resistance. Genotypes expressing the yellow fever mosquito Aedes aegypti Cyp9J28 while also bearing the paraV1016G mutation displayed substantially greater resistance ratio (RR) against deltamethrin than the product of each individual mechanism (RRcombined: 19.85 > RRCyp9J28: 1.77 × RRV1016G: 3.00). Genotypes expressing Brassicogethes aeneus pollen beetle Cyp6BQ23 and also bearing the paraL1014F (kdr) mutation, displayed an almost multiplicative RR (RRcombined: 75.19 ≥ RRCyp6BQ23: 5.74 × RRL1014F: 12.74). Reduced pyrethroid affinity at the target site, delaying saturation while simultaneously extending the duration of P450-driven detoxification, is proposed as a possible underlying mechanism. Combinations of target site and P450 resistance loci might be unfavourable in field populations in the absence of insecticide selection, as they exert some fitness disadvantage in development time and fecundity. These are major considerations from the insecticide resistance management viewpoint in both public health and agriculture. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the Royal Society B: Biological Sciences is the property of Royal Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: ‘What I cannot create, I do not understand’: functionally validated synergism of metabolic and target site insecticide resistance.
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  Data: <searchLink fieldCode="AR" term="%22Samantsidis%2C+George-Rafael%22">Samantsidis, George-Rafael</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Panteleri%2C+Rafaela%22">Panteleri, Rafaela</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Denecke%2C+Shane%22">Denecke, Shane</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kounadi%2C+Stella%22">Kounadi, Stella</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Christou%2C+Iason%22">Christou, Iason</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Nauen%2C+Ralf%22">Nauen, Ralf</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Douris%2C+Vassilis%22">Douris, Vassilis</searchLink><relatesTo>1,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Vontas%2C+John%22">Vontas, John</searchLink><relatesTo>1,5</relatesTo><i> vontas@imbb.forth.gr</i>
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  Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+Royal+Society+B%3A+Biological+Sciences%22">Proceedings of the Royal Society B: Biological Sciences</searchLink>. 5/27/2020, Vol. 287 Issue 1927, p1-10. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Insecticide+resistance%22">Insecticide resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Aedes+aegypti%22">Aedes aegypti</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+transformation%22">Genetic transformation</searchLink><br /><searchLink fieldCode="DE" term="%22Sodium+channels%22">Sodium channels</searchLink><br /><searchLink fieldCode="DE" term="%22CRISPRs%22">CRISPRs</searchLink><br /><searchLink fieldCode="DE" term="%22Malaria%22">Malaria</searchLink>
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  Data: The putative synergistic action of target-site mutations and enhanced detoxification in pyrethroid resistance in insects has been hypothesized as a major evolutionary mechanism responsible for dramatic consequences in malaria incidence and crop production. Combining genetic transformation and CRISPR/Cas9 genome modification, we generated transgenic Drosophila lines expressing pyrethroid metabolizing P450 enzymes in a genetic background along with engineered mutations in the voltage-gated sodium channel (para) known to confer target-site resistance. Genotypes expressing the yellow fever mosquito Aedes aegypti Cyp9J28 while also bearing the paraV1016G mutation displayed substantially greater resistance ratio (RR) against deltamethrin than the product of each individual mechanism (RRcombined: 19.85 > RRCyp9J28: 1.77 × RRV1016G: 3.00). Genotypes expressing Brassicogethes aeneus pollen beetle Cyp6BQ23 and also bearing the paraL1014F (kdr) mutation, displayed an almost multiplicative RR (RRcombined: 75.19 ≥ RRCyp6BQ23: 5.74 × RRL1014F: 12.74). Reduced pyrethroid affinity at the target site, delaying saturation while simultaneously extending the duration of P450-driven detoxification, is proposed as a possible underlying mechanism. Combinations of target site and P450 resistance loci might be unfavourable in field populations in the absence of insecticide selection, as they exert some fitness disadvantage in development time and fecundity. These are major considerations from the insecticide resistance management viewpoint in both public health and agriculture. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Proceedings of the Royal Society B: Biological Sciences is the property of Royal Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1098/rspb.2020.0838
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      – SubjectFull: Insecticide resistance
        Type: general
      – SubjectFull: Aedes aegypti
        Type: general
      – SubjectFull: Genetic transformation
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      – SubjectFull: Sodium channels
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      – SubjectFull: CRISPRs
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      – SubjectFull: Malaria
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      – TitleFull: ‘What I cannot create, I do not understand’: functionally validated synergism of metabolic and target site insecticide resistance.
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              Text: 5/27/2020
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