Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions

Abstract Resistance to pyrethroids is common in Aedes aegypti populations. Mutations in the voltage gated sodium channel have an influence on the insecticide resistance (IR) phenotype. In much of the Western hemisphere, two of these knockdown resistance (kdr) mutations, V1016I and F1534C, result in...

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Main Authors: Alden S. Estep, Neil D. Sanscrainte, Muhammad Farooq, Keira J. Lucas, Rebecca L. Heinig, Edmund J. Norris, James J. Becnel
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-94738-z
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author Alden S. Estep
Neil D. Sanscrainte
Muhammad Farooq
Keira J. Lucas
Rebecca L. Heinig
Edmund J. Norris
James J. Becnel
author_facet Alden S. Estep
Neil D. Sanscrainte
Muhammad Farooq
Keira J. Lucas
Rebecca L. Heinig
Edmund J. Norris
James J. Becnel
author_sort Alden S. Estep
collection DOAJ
description Abstract Resistance to pyrethroids is common in Aedes aegypti populations. Mutations in the voltage gated sodium channel have an influence on the insecticide resistance (IR) phenotype. In much of the Western hemisphere, two of these knockdown resistance (kdr) mutations, V1016I and F1534C, result in six kdr genotype combinations in field populations. Strong pyrethroid IR and the failure of permethrin treated uniforms have been linked to the presence of the homozygous double kdr genotype (IICC) but the effects of the other five kdr combinations have not been rigorously examined, particularly with regard to operational efficacy. To better understand the impacts of these common kdr genotypes, we isolated three kdr haplotypes (VF, VC, & IC) from a field collected strain to produce six Ae. aegypti isoline strains with all the common V1016I/F1534C kdr genotypes. We then characterized the effects of these genotypes by CDC bottle bioassay and topical application and found increasing resistance to permethrin and deltamethrin as the number of IC haplotypes increased. Neither enzymatic activity nor malathion resistance increased with increasing pyrethroid resistance. We then assessed the operational impacts of these kdr genotypes. Field and wind tunnel spray of a pyrethrin formulation showed that even moderate resistance could significantly reduce knockdown and mortality. Studies with a synergized pyrethroid formulation showed effective recovery of mortality against all genotypes except for the IICC. In human bite studies, one or two IC haplotypes compromised the efficacy of permethrin treated fabrics. This study demonstrates that kdr mutations have distinct phenotypic effects in both the laboratory and operational interventions, and that the strength of pyrethroid resistance varies with the number of IC haplotypes present. Assessing kdr genotype is therefore critical for understanding IR in Ae. aegypti.
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spelling doaj-art-9265417accad495fb3eb2425b92d4aa62025-08-20T02:49:34ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-94738-zImpact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventionsAlden S. Estep0Neil D. Sanscrainte1Muhammad Farooq2Keira J. Lucas3Rebecca L. Heinig4Edmund J. Norris5James J. Becnel6USDA-ARS Center for Medical Agricultural and Veterinary Entomology, Mosquito & Fly Research UnitUSDA-ARS Center for Medical Agricultural and Veterinary Entomology, Mosquito & Fly Research UnitAnastasia Mosquito Control DistrictCollier Mosquito Control DistrictCollier Mosquito Control DistrictUSDA-ARS Center for Medical Agricultural and Veterinary Entomology, Mosquito & Fly Research UnitUSDA-ARS Center for Medical Agricultural and Veterinary Entomology, Mosquito & Fly Research UnitAbstract Resistance to pyrethroids is common in Aedes aegypti populations. Mutations in the voltage gated sodium channel have an influence on the insecticide resistance (IR) phenotype. In much of the Western hemisphere, two of these knockdown resistance (kdr) mutations, V1016I and F1534C, result in six kdr genotype combinations in field populations. Strong pyrethroid IR and the failure of permethrin treated uniforms have been linked to the presence of the homozygous double kdr genotype (IICC) but the effects of the other five kdr combinations have not been rigorously examined, particularly with regard to operational efficacy. To better understand the impacts of these common kdr genotypes, we isolated three kdr haplotypes (VF, VC, & IC) from a field collected strain to produce six Ae. aegypti isoline strains with all the common V1016I/F1534C kdr genotypes. We then characterized the effects of these genotypes by CDC bottle bioassay and topical application and found increasing resistance to permethrin and deltamethrin as the number of IC haplotypes increased. Neither enzymatic activity nor malathion resistance increased with increasing pyrethroid resistance. We then assessed the operational impacts of these kdr genotypes. Field and wind tunnel spray of a pyrethrin formulation showed that even moderate resistance could significantly reduce knockdown and mortality. Studies with a synergized pyrethroid formulation showed effective recovery of mortality against all genotypes except for the IICC. In human bite studies, one or two IC haplotypes compromised the efficacy of permethrin treated fabrics. This study demonstrates that kdr mutations have distinct phenotypic effects in both the laboratory and operational interventions, and that the strength of pyrethroid resistance varies with the number of IC haplotypes present. Assessing kdr genotype is therefore critical for understanding IR in Ae. aegypti.https://doi.org/10.1038/s41598-025-94738-zAedes aegyptiInsecticide resistanceKnockdown resistance (kdr)Operational efficacyVoltage-gated sodium channel
spellingShingle Alden S. Estep
Neil D. Sanscrainte
Muhammad Farooq
Keira J. Lucas
Rebecca L. Heinig
Edmund J. Norris
James J. Becnel
Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
Scientific Reports
Aedes aegypti
Insecticide resistance
Knockdown resistance (kdr)
Operational efficacy
Voltage-gated sodium channel
title Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
title_full Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
title_fullStr Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
title_full_unstemmed Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
title_short Impact of Aedes aegypti V1016I and F1534C knockdown resistance genotypes on operational interventions
title_sort impact of aedes aegypti v1016i and f1534c knockdown resistance genotypes on operational interventions
topic Aedes aegypti
Insecticide resistance
Knockdown resistance (kdr)
Operational efficacy
Voltage-gated sodium channel
url https://doi.org/10.1038/s41598-025-94738-z
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