Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito .

With the spread of resistance to long-established insecticides targeting malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Ag1, Ag2, Ag3, Ag8 and Ag1 subunits in oocytes, the orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Ag2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Ag3 subunit increases it.

Aedes aegypti CCEae3A carboxylase expression confers carbamate, organophosphate and limited pyrethroid resistance in a model transgenic mosquito.

Insecticide resistance is a serious threat to our ability to control mosquito vectors which transmit pathogens including malaria parasites and arboviruses. Understanding the underlying mechanisms is an essential first step in tackling the challenges presented by resistance. This study aimed to functionally characterise the carboxylesterase, CCEae3A, the elevated expression of which has been implicated in temephos resistance in Aedes aegypti and Aedes albopictus larvae.