Pyrethroid resistance in mosquitoes

Repeated blood feedings throughout their life span have made mosquitoes ideal transmitters of a wide variety of disease agents. Vector control is a very important part of the current global strategy for the control of mosquito-associated diseases and insecticide application is the most important component in this effort. Pyrethroids, which account for 25% of the world insecticide market, are currently the most widely used insecticides for the indoor control of mosquitoes and are the only chemical recommended for the treatment of mosquito nets, the main tool for preventing malaria in Africa. However, mosquito-borne diseases are now resurgent, largely because of insecticide resistance that has developed in mosquito vectors and the anti-parasite drug resistance of parasites. This paper reviews our current knowledge of the molecular mechanisms governing metabolic detoxification and the development of target site insensitivity that leads to pyrethroid resistance in mosquitoes.

Gene expression profiles of the Southern house mosquito Culex quinquefasciatus during exposure to permethrin

Insecticide resistance is a major obstacle to the management of diseasevectoring mosquitoes worldwide. The genetic changes and detoxification genes involved in insecticide resistance have been extensively studied in populations of insecticide-resistant mosquitoes, however few studies have focused on the resistance genes upregulated upon insecticide exposure and the possible regulation pathways involved in insecticide resis- tance. To characterize the changes in gene expression during insecticide exposure, and to investigate the possible connection of known regulation pathways with insecticide resistance, we conducted RNA-Seq analysis of a highly permethrin-resistant strain of Culex quinquefasciatus following pcrmethrin exposure. Gene expression profiles revealed a total of 224 upregulated and 146 downregulated genes when compared to a blank acetone carrier treated control, respectively, suggesting that there were multiple, but specific genes involved in permethrin resistance. Functional enrichment analysis showed that the upregulated genes contained multiple detoxification genes including a glutathione S-transferase and multiple eytochrome P450 genes, as well as several immune-related genes, while the downregulated genes consisted primarily of proteases and carbohydrate metabolism and transport. Further analysis showed that permethrin exposure resulted in a decrease in the expression of serum storage proteins and likely represented a delay in the development of the fourth instar possibly due to a decrease in feeding. This effect was more pronounced in an insecticide-resistant strain than in an insecticide-susceptible strain and may represent a behavioral mechanism of insecticide resistance in Culex mosquitoes.

Sodium channel gene expression in mosquitoes, Aeries albopictus （S.）

A mosquito strain of Aedes albopictus, HAmAal^G0, from Huntsville, Alabama, USA, showed a normal susceptibility and low tolerance to permethrin and resmethrin （pyrethroid insecticides） compared to a susceptible Ikaken strain, even though these pyrethroid insecticides have been used in the field for a long period of time in Alabama. Recently, we treated HAmAal^G0 in the laboratory with permethrin for five generations and detected no significant change in the level of resistance to permethrin in the selected mosquitoes, HAmAal^G0, compared with the parental strain HAmAal^G0. We then examined the allelic expression at the L-to-F kdr site of the sodium channel gene in the Aedes mosquitoes to address our hypothesis that the L-to-F kdr mutation was not present in HAmAal^G0 and HAmAal^G5 mosquitoes. We found that every tested individual in Ikaken, HAmAal^G5, and HAmAal^G5 populations expressed a codon of CTA at the L-to-F kdr site encoding Leu, strongly corresponding to their susceptibility to insecticides.