Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel of Aedes aegypti: a potential challenge for mosquito control

Khalid Haddi,Eugênio E Oliveira,Hudson V V Tomé,Wilson R Valbon,Yuzhe Du,Ke Dong,Gustavo F Martins,Yoshiko Nomura

doi:10.1038/srep46549

Abstract

The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100–60,000 fold) of resistance to both type I and type II pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain. This study is the first report of the V410L mutation in mosquitoes. Alone or in combination with the F1534C mutation, the V410L mutation drastically reduced the sensitivity of mosquito sodium channels expressed in Xenopus oocytes to both type I and type II pyrethroids. The V410L mutation presents a serious challenge for the control of A. aegypti and will compromise the use of pyrethroids for the control of A. aegypti in Brazil; therefore, early monitoring of the frequency of the V410L mutation will be a key resistance management strategy to preserve the effectiveness of pyrethroid insecticides.

Highlights

Aedes aegypti is the primary vector for Zika and dengue worldwide and has high vectorial capacity for chikungunya and yellow fever arboviruses[2,4,5]
We report on a Brazilian strain of A. aegypti with high levels of pyrethroid resistance conferred primarily by kdr (i.e., V410L and F1534C) mutations, especially in adult mosquitoes
The V410L mutation is reported for the first time in the sodium channels of mosquitoes, and by identifying the valine to leucine substitution at a corresponding position in a mosquito (i.e., AaNav1-1) sodium channel, we demonstrated that this amino acid substitution reduced the sensitivity of these channels to both type I and type II pyrethroids

Summary

Introduction

Aedes aegypti is the primary vector for Zika and dengue worldwide and has high vectorial capacity for chikungunya and yellow fever arboviruses[2,4,5]. Among the various compounds (e.g., organophosphates and neonicotinoids for control of larvae and adults and insect growth regulators (IGR) and Bacillus-based compounds for control of larvae) recommended by the World Health Organization (WHO) in the effort to control mosquitoes, pyrethroid insecticides are one of most important because of their efficacy and safety[1,2,3,4,5] Pyrethroids exert their toxic effects by disrupting the functionalities of the voltage-gated sodium channels in the insect nervous system[6,7,8,9]. For the first time in mosquitoes, we describe a valine to leucine substitution (V410L) in the transmembrane segment 6 of domain I that contributed to high levels of resistance to both types (i.e., I and II) of pyrethroids The prevalence of this mutation represents a new challenging factor for the control of A. aegypti

Methods

Results

Conclusion