Molecular mechanisms associated with increased tolerance to the neonicotinoid insecticide imidacloprid in the dengue vector Aedes aegypti

• Published in: Aquatic toxicology Vol. 126; no. 15; pp. 326 - 337
• Main Authors: Riaz, Muhammad Asam, Chandor-Proust, Alexia, Dauphin-Villemant, Chantal, Poupardin, Rodolphe, Jones, Christopher M., Strode, Clare, Régent-Kloeckner, Myriam, David, Jean-Philippe, Reynaud, Stéphane
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.01.2013; Elsevier
• Subjects: adults; Aedes - drug effects; Aedes - genetics; Aedes - metabolism; Aedes aegypti; Animal, plant and microbial ecology; Animals; Applied ecology; Bemisia tabaci; bioassays; Biological and medical sciences; carbamates; Cluster Analysis; cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; dengue; Detoxification enzymes; disease control; Drosophila melanogaster; Ecotoxicology, biological effects of pollution; enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; General aspects; genes; hexamerins; human diseases; Imidacloprid; Imidazoles - metabolism; Imidazoles - toxicity; Increased tolerance; Insect Vectors - genetics; Insect Vectors - metabolism; Insecticide Resistance - genetics; Insecticides - metabolism; Insecticides - toxicity; insects; Larva - drug effects; Larva - genetics; larvae; Medically important nuisances and vectors, pests of stored products and materials: population survey and control; metabolism; Microarray; microsomes; Mosquito; NADP (coenzyme); Neonicotinoids; Nitro Compounds - metabolism; Nitro Compounds - toxicity; organophosphorus compounds; pyrethrins; transcription (genetics); Transcriptome; transcriptomics; transferases; vector control; Vectors. Intermediate hosts; Detoxification enzymes; Increased tolerance; Imidacloprid; Microarray; Mosquito; Nitro compound; Insecticide; Toxicity; Insecta; Systemic; Aquatic environment; Neonicotinoid; Arbovirus disease; Vector; Ecotoxicology; Enzyme; Dengue; Pesticides; Detoxification; Parasite; Tolerance; Guanidines; Infection; Arthropoda; Viral disease; Culicidae; Aedes aegypti; Ectoparasite; Invertebrata; Diptera
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2012.09.010

► A strain of Aedes aegypti was selected at the larval stage with imidacloprid. ► The selected strain showed a 5.4-fold increased tolerance to imidacloprid at G8. ► 344 genes were differentially transcribed in larvae from the resistant strain. ► 24 P450s showed a significant differential transcription in larvae or adults. ► Imidacloprid docking models suggest that 2 P450 may contribute to resistance. Mosquitoes are vectors of several major human diseases and their control is mainly based on the use of chemical insecticides. Resistance of mosquitoes to organochlorines, organophosphates, carbamates and pyrethroids led to a regain of interest for the use of neonicotinoid insecticides in vector control. The present study investigated the molecular basis of neonicotinoid resistance in the mosquito Aedes aegypti. A strain susceptible to insecticides was selected at the larval stage with imidacloprid. After eight generations of selection, larvae of the selected strain (Imida-R) showed a 5.4-fold increased tolerance to imidacloprid while adult tolerance level remained low. Imida-R larvae showed significant cross-tolerance to other neonicotinoids but not to pyrethroids, organophosphates and carbamates. Transcriptome profiling identified 344 and 108 genes differentially transcribed in larvae and adults of the Imida-R strain compared to the parental strain. Most of these genes encode detoxification enzymes, cuticle proteins, hexamerins as well as other proteins involved in cell metabolism. Among detoxification enzymes, cytochrome P450 monooxygenases (CYPs) and glucosyl/glucuronosyl transferases (UDPGTs) were over-represented. Bioassays with enzyme inhibitors and biochemical assays confirmed the contribution of P450s with an increased capacity of the Imida-R microsomes to metabolize imidacloprid in presence of NADPH. Comparison of substrate recognition sites and imidacloprid docking models of six CYP6s over-transcribed in the Imida-R strain together with Bemisia tabaci CYP6CM1vQ and Drosophila melanogaster CYP6G1, both able to metabolize imidacloprid, suggested that CYP6BB2 and CYP6N12 are good candidates for imidacloprid metabolism in Ae. aegypti. The present study revealed that imidacloprid tolerance in mosquitoes can arise after few generations of selection at the larval stage but does not lead to a significant tolerance of adults. As in other insects, P450-mediated insecticide metabolism appears to play a major role in imidacloprid tolerance in mosquitoes.