Resistance to pirimiphos-methyl in West AfricanAnophelesis spreading via duplication and introgression of theAce1locus

Abstract

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from CoB te d'Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 and substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa probably due to cross-resistance with previously used insecticides. Our findings highlight the phenotypic value of this complex resistance haplotype and clarify its evolutionary history, providing tools to understand the current and future effectiveness of pirimiphos-methyl based interventions.

Overabundance of Asaia and Serratia Bacteria Is Associated with Deltamethrin Insecticide Susceptibility in Anopheles coluzzii from Agboville, Côte d’Ivoire

“…Control of insecticide-resistant vector populations is predicated on a clear understanding of the complex interplay between molecular mechanisms and fitness costs which contribute to mosquito behavior, phenotype and vectorial capacity, the genetic and local environmental factors driving ongoing resistance selection, and the implications of resistance for intervention operational efficacy. Substantial progress has been made elucidating key target site mutations ( 4 – 7 ), overexpression of detoxification enzymes ( 8 – 12 ) and alternate gene families and pathways ( 13 – 17 ), all of which play important roles in resistance modulation. Furthermore, the recent publication of genome data for more than 1,000 Anopheles ( An .)…”

Molecular drivers of insecticide resistance in the Sahelo-Sudanian populations of a major malaria vectorAnopheles coluzzii

“…The G280S/G119S ace -1 mutation, found in high frequencies across Sahel confers organophosphate an carbamates resistance (Weill et al, 2004), and is shown recently to confer resistance to pirimiphos-methyl, in An. coluzzii / gambiae (Grau-Bove et al, 2021). Several mutations found within the VGSC have recently been described/validated.…”

Perspectives on gene copy number variation and pesticide resistance

“…Different configurations have different fitness costs in the absence of insecticide, and a variant that deletes the 11 other co‐amplified genes but not Ace‐1 (termed ‘adaptive deletion’) is spreading in West Africa and introgressing into the closely related species An. coluzzii 11,12 . In the spider mite Tetranychus evansi , a point mutation in Ace‐1 conferring insensitivity to chlorpyrifos also confers a lower fitness in the absence of the insecticide, which is compensated for by an increase to eight to ten copies in some resistant strains 13 .…”