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Résistance du moustique Anopheles gambiae à Fludora® Fusion, une nouvelle combinaison d’insecticides à double mode d’action utilisable en pulvérisation intra domiciliaire. Réponse adaptative et interactions gènes-environnement

Abstract : To overcome the spread of pyrethroid resistance in malaria vectors, Bayer has recentlydeveloped a new insecticide formulation (Fludora® Fusion) combining the insecticidesdeltamethrin (class II pyrethroids) and clothianidin (neonicotinoid) for indoor residual spraying.Although this novel combination showed a good efficacy on Anopheles mosquitoes, its longtermefficacy has not yet been evaluated. In this context, the present thesis aimed at studying,across multiple generations, the dynamics of resistance upon a controlled selection withFludora® Fusion or its two insecticide components in An. gambiae and investigate theunderlying mechanisms through a transcriptomic approach. In parallel, the impact of a sublethalexposure of larvae to agrochemicals on the tolerance of adults to Fludora® Fusion andits two insecticide components was performed.A field-derived An. gambiae line carrying resistance alleles to multiple insecticide familiesat low frequencies was selected in the laboratory for multiple generations with Fludora®Fusion, deltamethrin alone or clothianidin alone. This study confirmed the potential ofFludora® Fusion to prevent the selection of resistance as compared to deltamethrin orclothianidin alone. Deltamethrin selection led to the rapid rise of resistance in link with theselection of the Kdr L1014F target-site mutation. Selection with clothianidin alone also led tothe emergence of metabolic resistance associated with detoxification enzymes includingcytochromes P450 (CYP genes). Polymorphism data pinpointed a strong selection signatureassociated with clothianidin resistance affecting a large CYP cluster previously associated withresistance. Subsequent analyses suggested that the over-expression and the selection of aparticular variant of the gene CYP6M1 are associated with the observed resistance phenotype.Regarding the impact of environment on Fludora® Fusion, the exposure of An. gambiaelarvae to a sub-lethal dose of an agrochemical mixture led to an increased tolerance to Fludora®Fusion and clothianidin in adult females suggesting that Fludora® Fusion efficacy mainly relieson clothianidin which can be affected by the presence of agrochemicals. A transcriptomicanalysis performed in larvae exposed or not and in adults obtained from these larvae revealedan over-transcription of multiple genes encoding cuticle proteins and cytochromes P450 amongwhich some were previously associated with clothianidin resistance.Overall this thesis confirmed the added value of Fludora® Fusion in vector control and itspotential in terms of resistance management. This work also suggest that the use ofneonicotinoids alone can select for resistance in mosquitoes as previously observed in croppests, and a significant impact of agrochemicals on the tolerance of mosquitoes to thisinsecticide family.
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Submitted on : Wednesday, June 29, 2022 - 1:02:16 AM
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Gonsé Marius Zoh. Résistance du moustique Anopheles gambiae à Fludora® Fusion, une nouvelle combinaison d’insecticides à double mode d’action utilisable en pulvérisation intra domiciliaire. Réponse adaptative et interactions gènes-environnement. Biodiversité. Université Grenoble Alpes [2020-..], 2021. Français. ⟨NNT : 2021GRALV030⟩. ⟨tel-03708133⟩

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