Researchers have found how the unprecedented multiple and extreme-level resistance is generated in mosquitoes found in the rice fields of Tiassale in southern Cote d'Ivoire.
The new work reveals that two members of the P450 gene superfamily in particular are highly expressed in resistant Tiassale mosquitoes: CYP6M2 and CYP6P3.
When these genes were transplanted into Drosophila, resistance to pyrethroids and carbamates was generated in otherwise susceptible fly strains. These genes are familiar candidates to LSTM researchers who have previously documented their links with pyrethroid and DDT resistance.
This new research shows how specific P450 genes can engender resistance across insecticides with entirely different modes of action: DDT and pyrethroids target a voltage-gated sodium channel (a nerve cell membrane channel), whereas carbamates and organophosphates target the neurotransmitter Acetylcholinesterase, encoded by the gene ACE-1. This is where Tiassale mosquitoes yielded another surprise, contributing to their exceptionally high carbamate resistance.
A well-known single nucleotide resistance mutation at the ACE-1 gene is near ubiquitous in the population, but because almost every female is a heterozygote (possesses a resistant and susceptible allele) it did not seem this could cause any variation in resistance. However, from application of a newly-developed qPCR diagnostic it was found that the ACE-1 gene was duplicated in some individuals, with those resistant to carbamate much more likely to have additional, duplicated copies of the resistant ACE-1 allele.
The study has been published in journal PLoS Genetics.
