The F1534C voltage‐sensitive sodium channel mutation confers 7‐ to 16‐fold resistance to pyrethroid insecticides in Aedes aegypti

Abstract

BACKGROUND: Recent outbreaks of dengue and Zika have emphasized the importance to effectively control Aedes aegypti, which vectors the viruses causing these diseases. Pyrethroid insecticides are primarily used to control adult A. aegypti, especially during disease outbreaks. However, pyrethroid resistance in A. aegypti is an increasing problem. Mutations in the voltage-sensitive sodium channel (Vssc) are a common mechanism of pyrethroid resistance. The F1534C mutation is common and distributed globally in A. aegypti populations, but previous studies disagree about the role of this mutation in conferring resistance to pyrethroid insecticides. RESULTS:We isolated a congenic strain (1534C:ROCK) which was closely related to a susceptible strain Rockefeller (ROCK), but was homozygous for the 1534C Vssc allele. We determined resistance levels against eight insecticides that target the VSSC: six pyrethroids, DDT and DCJW (the bioactivated metabolite of indoxacarb). The resistance levels ranged from 7-to 16-fold, and resistance was inherited as an incompletely recessive trait. We also found a novel 367I+1520I+1534C allele, in addition to the 1534C and 1520I+1534C alleles, in mosquitoes from Thailand. The T1520I mutation did not increase pyrethroid resistance beyond what was conferred by the F1534C mutation alone. CONCLUSION: The F1534C Vssc mutation is common in A. aegypti populations and confers 7-to 16-fold resistance to pyrethroids, DDT, and DCJW in Aedes aegypti. These resistance levels are considerably less than previously reported for the S989P+V1016G mutations. Our results provide useful information for resistance management, specifically the levels of resistance conferred by the most common Vssc mutation in A. aegypti.

A first, naturally occurring substitution at the second pyrethroid receptor of voltage‐gated sodium channel of Aedes aegypti

“…V1016I (V1023I in some studies) is another kdr variant common in Latin America, along with the F1534C substitution 9 . A congenic strain that inherited the F1534C haplotype from Thailand in the susceptible strain (ROCK) genetic background exhibited seven‐fold and 16‐fold resistance against permethrin (a type I pyrethroid) and deltamethrin (a type II pyrethroid), respectively 10 . The contribution of F1534C on the deltamethrin resistance phenotype, however, is still debatable.…”

Permethrin resistance in Aedes aegypti: Genomic variants that confer knockdown resistance, recovery, and death

“…aegypti . Three kdr -mutations are common in Latin America, including V410L, V1016I, and F1534C [ 6 – 8 ]. The role of V410L and F1534C to confer pyrethroid resistance was recently confirmed in electrophysiological assays [ 8 , 9 ].…”

Association Between Pyrethrum Knockdown Time and Sodium Channel Genotypes in California Aedes Aegypti

“…Given the functional evidence in the literature, and our assay results (Fig. 4-5), the increasing prevalence of the F1534C mutation, particularly in combination with V410L and V1016I reliably indicates an elevated level of resistance to type I pyrethroids (7,13,31,47). However, the individual bottle assays employed here prompts us to question that, assuming good conditions, the presence of resistance alleles in the VGSC gene may not guarantee adulticide failure, and susceptible alleles may not ensure control success.…”

“…The Xenopus oocyte expression system for Ae. aegypti sodium channels has facilitated investigation into the role of individual mutations assayed in pyrethroid resistance (13,31,46,47). The mutations V410L + F1534C and V1016I + F1534C have even been studied in combination (13,16,47).…”

“…aegypti sodium channels has facilitated investigation into the role of individual mutations assayed in pyrethroid resistance (13,31,46,47). The mutations V410L + F1534C and V1016I + F1534C have even been studied in combination (13,16,47). Little is known about the S723T mutation (48) though with the high frequency of this mutation in all populations tested (59% in Greater LA and > 92% in all Central Valley populations, Table 1), future functional analyses would be important to understanding the role this mutation plays in resistance.…”