Reversing insecticide resistance with allelic-drive in Drosophila melanogaster

Bhagyashree Kaduskar, Raja Babu Singh Kushwah, Ankush Auradkar, Annabel Guichard, Menglin Li, Jared B. Bennett, Alison Henrique Ferreira Julio, John M. Marshall, Craig Montell and Ethan Bier ()
Additional contact information
Bhagyashree Kaduskar: Center at inStem
Raja Babu Singh Kushwah: Center at inStem
Ankush Auradkar: University of California, San Diego
Annabel Guichard: University of California, San Diego
Menglin Li: University of California
Jared B. Bennett: University of California
Alison Henrique Ferreira Julio: Universidade Federal do Rio de Janeiro
John M. Marshall: University of California
Craig Montell: University of California
Ethan Bier: University of California, San Diego

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-021-27654-1

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