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Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel of Aedes aegypti: a potential challenge for mosquito control.
Haddi K
,
Tomé HVV
,
Du Y
,
Valbon WR
,
Nomura Y
,
Martins GF
,
Dong K
,
Oliveira EE
.
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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.
Figure 1. Toxicity (a,b) and comparative effects of synergists (c,d) on mortality caused by permethrin and deltamethrin to larvae (L4) of two Brazilian strains of Aedes aegypti. (a,b) The lines denote the lethal concentration (LC) values estimated based on concentration-mortality bioassays using probit analyses. Symbols show the averaged mortality for each insecticide concentration applied to each population of A. aegypti. The vertical bars represent the standard error of the average (SE). (c,d) The effects of the synergists piperonyl butoxide (PBO), diethyl maleate (DEM) and triphenyl phosphate (TPP) on the mortality of the resistant population caused by pyrethroids at the LC50 obtained for the resistant strain. Asterisks indicate significant differences in relation to the unsynergized insecticide (one-way ANOVA with Scheffeâs post hoc analysis, Pâ<â0.05).
Figure 2. Toxicity (a,b) and comparative effects of synergists (c,d) on mortality caused by permethrin and deltamethrin to adults of two Brazilian strains of Aedes aegypti. (a,b) The lines denote the lethal concentration (LC) values estimated based on concentration-mortality bioassays using probit analyses. Symbols show the averaged mortality for each insecticide concentration applied to each population of A. aegypti. The vertical bars represent the standard error of the average (SE). (c,d) The effects of the synergists piperonyl butoxide (PBO), diethyl maleate (DEM) and triphenyl phosphate (TPP) on the mortality of the resistant population caused by pyrethroids at the LC50 obtained for the resistant strain. Asterisks indicate significant differences in relation to the unsynergized insecticide (one-way ANOVA with Scheffeâs post hoc analysis, Pâ<â0.05).
Figure 3. Pyrethroid resistance-associated amino acid substitutions in A. aegypti sodium channels. (a) Schematic representation of the mosquito sodium channel protein (AaNav1-1) indicating two knockdown resistance mutations in IS6 and IVS6. Sodium channels are large transmembrane proteins with four homologous repeats (IâIV), each having six transmembrane segments (S1âS6). Residue positions correspond to the cockroach BgNav protein (GenBank number: U73583). Dose-response curves of permethrin (b) and deltamethrin (c) on BgNav1-1a, V410L, F1534C and V410Lâ+âF1534C cockroach sodium channels. The method for determining the percentage of modified channels is described in the Materials & Methods section.
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