Abstract
Pyrethroids are the most used insecticide class worldwide. They target the voltage gated sodium channel (NaV), inducing the knockdown effect. In Aedes aegypti, the main dengue vector, the AaNaV substitutions Val1016Ile and Phe1534Cys are the most important knockdown resistance (kdr) mutations. We evaluated the fitness cost of these kdr mutations related to distinct aspects of development and reproduction, in the absence of any other major resistance mechanism. To accomplish this, we initially set up 68 crosses with mosquitoes from a natural population. Allele-specific PCR revealed that one couple, the one originating the CIT-32 strain, had both parents homozygous for both kdr mutations. However, this pyrethroid resistant strain also presented high levels of detoxifying enzymes, which synergistically account for resistance, as revealed by biological and biochemical assays. Therefore, we carried out backcrosses between CIT-32 and Rockefeller (an insecticide susceptible strain) for eight generations in order to bring the kdr mutation into a susceptible genetic background. This new strain, named Rock-kdr, was highly resistant to pyrethroid and presented reduced alteration of detoxifying activity. Fitness of the Rock-kdr was then evaluated in comparison with Rockefeller. In this strain, larval development took longer, adults had an increased locomotor activity, fewer females laid eggs, and produced a lower number of eggs. Under an inter-strain competition scenario, the Rock-kdr larvae developed even slower. Moreover, when Rockefeller and Rock-kdr were reared together in population cage experiments during 15 generations in absence of insecticide, the mutant allele decreased in frequency. These results strongly suggest that the Ae. aegypti kdr mutations have a high fitness cost. Therefore, enhanced surveillance for resistance should be priority in localities where the kdr mutation is found before new adaptive alleles can be selected for diminishing the kdr deleterious effects.
Highlights
Diseases like dengue, malaria, lymphatic filariasis, leishmaniasis and Chagas’ disease are caused by pathogens transmitted by insect vectors and represent a significant part of all morbidity and mortality records in tropical countries
Besides homozygous for alteration in the pyrethroid target site, this strain displayed highly altered activity of enzymes related to metabolic resistance, a-EST, pNPA-EST and glutathione-S transferases (GST), when compared to the susceptible reference Rockefeller strain, Rock (Figure 1, Cachoeiro do Itapemirim (CIT)-32)
Since we aimed to determine the actual role of the kdr mutation on resistance and assess its fitness cost, it was necessary to reduce the contribution of metabolic resistance
Summary
Malaria, lymphatic filariasis, leishmaniasis and Chagas’ disease are caused by pathogens transmitted by insect vectors and represent a significant part of all morbidity and mortality records in tropical countries. Pyrethroids are by far the most popular insecticide class, in terms of surface area [5], against adult mosquitoes since they act very rapidly (the knockdown effect), are applied and less harmful to both the environment and man. Up to now, they are the only class of products recommended by the World Health Organization (WHO) for use in insecticide treated materials (ITMs), which are currently largely distributed for personal protection against malaria and dengue vectors [6,7]. Insecticide resistant populations are spreading all over the world, representing a growing obstacle to vector control programs [8]
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