Alanine to glycine substitution in the PyR2 confers sodium channel resistance to Type I pyrethroids

Abstract

BACKGROUNDAedes aegypti is a primary urban vector of dengue, yellow fever, Zika and chikungunya worldwide. Pyrethroid insecticides are the most effective insecticides for controlling Ae. aegypti. However, pyrethroid resistance has developed due to the long‐term overuse of the insecticides, and many knockdown resistance (kdr) mutations have been identified in the resistant populations. A1007G, an alanine to glycine substitution, was found in resistant Ae. aegypti from Vietnam and Malaysia, which has always co‐existed with F1534C and V1016G. However, the role of A1007G in pyrethroid resistance and the linkage of A1007G and F1534C or V1016G remain unknown.RESULTSIn this study, we examined the effects of mutations on the sodium channel gating properties and pyrethroid sensitivity in Xenopus oocytes. We found mutations A1007G, A1007G + F1534C and A1007G + V1016G + F1534C shifted the voltage dependence of activation in the depolarizing direction. Mutations A1007G + F1534C and A1007G + V1016G + F1534C shifted the voltage dependence of inactivation in the depolarizing direction. Both mutations A1007G and F1534C reduced the channel sensitivity to two Type I pyrethroids, permethrin and bifenthrin, and synergistic effects were observed between mutations A1007G and F1534C. However, none of the mutations, A1007G, F1534C and A1007G + F1534C affected the channel sensitivity to two Type II pyrethroids, deltamethrin and cypermethrin. Furthermore, triple mutations A1007G + V1016G + F1534C significantly reduced the channel sensitivity to both Type I and Type II pyrethroids.CONCLUSIONWe identified A1007G had a distinct effect on sodium channel sensitivity to Type I, but not to Type II pyrethroids, also A1007G exhibited synergistic effects with F1534C to Type I pyrethroids, which will provide a fundamental insight into the distinct molecular interactions between insect sodium channel and Type I or Type II pyrethroids. © 2024 Society of Chemical Industry.