Acetylcholinesterase (Ace-1) target site mutation 119S is strongly diagnostic of carbamate and organophosphate resistance in Anopheles gambiae s.s. and nopheles coluzzii across southern Ghana

Abstract

Background : With high DDT resistance present throughout much of West Africa, carbamates and organophosphates are increasingly important alternatives to pyrethroids for indoor residual spraying (IRS). Hough less widespread, resistance to both of these alternative insecticide classes has also been documented within the Anopheles gambiae species pair (formerly the M and S molecular forms) in West Africa. o manage insecticide efficacy, it is important to predict how and where resistance is likely to occur and spread, which could be aided by using molecular diagnostics with high predictive value. Methods : Anopheles coluzziiand An. gambiae s.s.were collected from 18 sites throughout southern Ghana and bioassayed with bendiocarb, the most commonly applied carbamate, and an organophosphate, fenitrothion. He Ace-1target site substitution G119S was genotyped by qPCR. Results:Fenitrothion induced higher mortality than bendiocarb, though phenotypes correlated strongly across populations.Ace-1119S was found at much higher frequency inAn. gambiae s.s thanAn. coluzzii, exceeding 90% in a population from Greater Accra, the highest frequency reported to date.Ace-1G119S was very strongly associated with resistance to both insecticides, providing high predictive power for diagnosis, though with some evidence for a differential effect between molecular forms for bendiocarb. Sequencing of the gene revealed a lack of variation in resistant alleles precluding determination of origin, but Ace-1copy number variation was detected for the first time in Ghana. Conclusions : The results validate G119S as a useful diagnostic of organophosphate and carbamate resistance within and among populations, whilst highlighting the potential for an aggregate nature of Ace-1genotypes, which may comprise both single-copy and duplicated genes. Further work is now required to determine the distribution and resistance-association of Ace-1duplication