Reversing insecticide resistance with allelic-drive in Drosophila melanogaster

• Published in: Nature communications Vol. 13; no. 1; p. 291
• Main Authors: Kaduskar, Bhagyashree, Kushwah, Raja Babu Singh, Auradkar, Ankush, Guichard, Annabel, Li, Menglin, Bennett, Jared B., Julio, Alison Henrique Ferreira, Marshall, John M., Montell, Craig, Bier, Ethan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 42/41; 45/70; 631/208/2156; 631/61/17/1511; 64/24; Alleles; Animals; CRISPR; CRISPR-Cas Systems; Culicidae; DDT; Deltamethrin; Directional control; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Female; Fruit flies; Genetic Engineering; Global health; Humanities and Social Sciences; Insecticide resistance; Insecticide Resistance - genetics; Insecticides; Insects; Laboratories; Malaria; Male; multidisciplinary; Mutation; Parasite resistance; Parasites; Permethrin; Pesticide resistance; Pests; Public health; Pyrethroids; Reversion; Science; Science (multidisciplinary); Sodium channels (voltage-gated); Vector-borne diseases; Vectors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27654-1

A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel ( vgsc ) gene (often referred to as knockdown resistance or kdr ) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate common kdr mutations in isogenic laboratory Drosophila strains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two different kdr mutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistant kdr mutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles. Insecticide resistance (IR) poses a major global health challenge. Here, the authors generate common IR mutations in laboratory Drosophila strains and use a CRISPR-based allelic-drive to replace an IR allele with a susceptible wild-type counterpart, providing a potent new tool for vector control.