Mosquitoes are vectors of numerous human pathogens that kill or debilitate millions of humans each year. Because A. aegypti vectors four important human disease viruses, has a wide global distribution and thrives in urban environments, it poses a serious risk to human health. Pyrethroid insecticides have been and are widely used for A. aegypti control and their extensive use has resulted in resistance that is now found worldwide. Insecticide resistance is a major obstacle to the control of medically significant arthropod pests. To effectively manage the evolution of resistance it is important to know the levels of resistance conferred by specific mutations. To study the contributions of the different resistance mechanisms, we have created three pyrethroid resistant strains of A. aegypti that have the same genetic background as the susceptible ROCK strain: KDR:ROCK contains a pair of Vssc mutations S989P+V1016G (referred to as kdr), but no metabolic detoxification resistance; CYP:ROCK has cytochrome P450 (CYP)-mediated resistance but no kdr; and CYP+KDR:ROCK has both kdr and CYP-mediated resistance. Insecticide resistance of the individual and combined resistance mechanisms, kdr and CYP-mediated detoxification, were assessed by performing bioassays using structurally diverse pyrethroids on the three congenic strains and ROCK. Cross- and negative cross-resistance to organophosphates (OPs) was also assessed for the two strains containing CYP-mediated resistance. Our results indicate that there is a near multiplicative (more than additive) contribution to resistance to some pyrethroids when both mechanisms are combined. We found that resistance levels varied significantly and that CYP-mediated resistance confers negative-cross resistance to some OPs. We also evaluated the contribution of kdr to resistance to two other classes of insecticides targeting VSSC (DDT and oxadiazines) and found that kdr has significant cross-resistance to DDT (&gt; 2000-fold) and oxadiazines (13-38-fold). The implications of these results to the control of A. aegypti will be discussed.

Comparison of the patterns of resistance and cross-resistance to insecticides conferred by the two major mechanisms of pyrethroid resistance in Aedes aegypti

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.