The G119S Acetylcholinesterase (Ace-1) Target Site Mutation Confers Carbamate Resistance in the Major Malaria Vector Anopheles gambiae from Cameroon: A Challenge for the Coming IRS Implementation

Abstract

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (<i>Ace-1</i>) to this resistance remains uncharacterised. Here, we established that the <i>G119S</i> mutation is driving resistance to carbamates in <i>Anopheles gambiae</i> populations from Cameroon. Insecticide bioassay on field-collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8% ± 3.5% mortality) and propoxur (55.71% ± 2.9%) but a full susceptibility to the organophosphate fenitrothion. The TaqMan genotyping of the <i>G119S</i> mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the <i>Ace-1</i>^R and carbamate resistance at allelic ((bendiocarb; odds ratio (OR) = 75.9; <i>p</i> < 0.0001) and (propoxur; OR = 1514; <i>p</i> < 0.0001)) and genotypic (homozygote resistant vs. homozygote susceptible (bendiocarb; OR = 120.8; <i>p</i> < 0.0001) and (propoxur; OR = 3277; <i>p</i> < 0.0001)) levels. Furthermore, the presence of the mutation was confirmed by sequencing an <i>Ace-1</i> portion flanking codon 119. The cloning of this fragment revealed a likely duplication of <i>Ace-1</i> in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant <i>Ace-1</i>^R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this <i>Ace-1</i>^R represents a serious challenge to future implementation of indoor residual spraying (IRS)-based interventions using carbamates or organophosphates in Cameroon.