Genomic analysis of detoxification genes in the mosquito Aedes aegypti

Pyrethroid resistance in Aedes aegypti and Aedes albopictus: Important mosquito vectors of human diseases

The use of chemical insecticides continues to play a major role in the control of disease vector populations, which is leading to the global dissemination of insecticide resistance. A greater capacity to detoxify insecticides, due to an increase in the expression or activity of three major enzyme families, also known as metabolic resistance, is one major resistance mechanisms. The esterase family of enzymes hydrolyse ester bonds, which are present in a wide range of insecticides; therefore, these enzymes may be involved in resistance to the main chemicals employed in control programs. Historically, insecticide resistance has driven research on insect esterases and schemes for their classification. Currently, several different nomenclatures are used to describe the esterases of distinct species and a universal standard classification does not exist. The esterase gene family appears to be rapidly evolving and each insect species has a unique complement of detoxification genes with only a few orthologues across species. The examples listed in this review cover different aspects of their biochemical nature. However, they do not appear to contribute to reliably distinguish among the different resistance mechanisms. Presently, the phylogenetic criterion appears to be the best one for esterase classification. Joint genomic, biochemical and microarray studies will help unravel the classification of this complex gene family.

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The classification of esterases: an important gene family involved in insecticide resistance - A review

Organophosphates and pyrethroids are used widely in Brazil to control Aedes aegypti, the main vector of dengue viruses, under the auspices of the National Programme for Dengue Control. Resistance to these insecticides is widespread throughout Brazil. In Ceara the vector is present in 98% of districts and resistance to temephos has been reported previously. Here we measure resistance to temephos and the pyrethroid cypermethrin in three populations from Ceara and use biochemical and molecular assays to characterise resistance mechanisms. Resistance to temephos varied widely across the three studied populations, with resistance ratios (RR95) of 7.2, 30 and 192.7 in Juazeiro do Norte, Barbalha and Crato respectively. The high levels of resistance detected in Barbalha and Crato (RR95 ≥ 30) imply a reduction of temephos efficacy, and indeed in simulated field tests reduced effectiveness was observed for the Barbalha population. Two populations (Crato and Barbalha) were also resistant to cypermethrin, whilst Juazeiro do Norte showed only an altered susceptibility. The Ile1011Met kdr mutation was detected in all three populations and Val1016Ile in Crato and Juazeiro do Norte. 1011Met was significantly associated with resistance to cypermethrin in the Crato population. Biochemical tests showed that only the activity of esterases and GSTs, among the tested detoxification enzymes, was altered in these populations when compared with the Rockefeller strain. Our results demonstrate that two A. aegypti populations from Ceara are under strong selection pressure by temephos, compromising the field effectiveness of this organophosphate. Our results also provide evidence that the process of reducing resistance to this larvicide in the field is difficult and slow and may require more than seven years for reversal. In addition, we show resistance to cypermethrin in two of the three populations studied, and for the first time the presence of the allele 1016Ile in mosquito populations from northeastern Brazil. A significant association between 1011M et and resistance was observed in one of the populations. Target-site mechanisms seem not to be implicated in temephos resistance, reinforcing the idea that for the studied populations, detoxification enzymes most likely play a major role in the resistance to this insecticide.

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Insecticide resistance in Aedes aegypti populations from Ceará, Brazil

Background: Most national dengue control programmes rely extensively on insecticides to control the mosquito vectors of this disease.
Objectives: The objective of this review is to describe current knowledge of the extent of insecticide resistance in dengue vectors and the potential impact of this resistance on control activities.
Methods: We searched Web of Science and PubMed for studies that included data on resistance to the four major classes of insecticides: organochlorines, carbamates, organophosphates and pyrethroids, in the dengue vectors Aedes aegypti and Aedes albopictus. Insecticide bioassy data were extracted from the published literature and the methods used to obtain, analyse and interpret this data were critically evaluated. Emphasis was placed on the two insecticide classes most widely used in dengue control, organophosphates and pyrethroids. The use of biochemical and molecular tools for resistance monitoring was also reviewed.
Results: 66 studies met our inclusion criteria and were uploaded on to a public databse (IRBase). There is a stong geographical bias in published studies with nearly half originating from three countries (Thailand, India and Brazil). Bioassay data demonstrates that resistance to the organophosphate temephos and to pyrethroids is widespread in Ae. aegypti and resistance has also been reported in Ae. albopictus. Assessing the impact of insecticide resistance on vector control is complicated by variations in the methodology used to measure and report resistance, and by the lack of studies into the epidemiological consequences of insecticicde resistance.
Conclusions: The lack of publicly accessible standardized data sets dcoumenting levels of insecticide resistance in many dengue endemic countries, and the absence of studies on the operational impact of resistance, preculdes a comprehensive analysis of the current global threat that insecticide resistance poses to dengue control. However, several countries with active resistance monitoring programmes have shown that insecticide resistance is reducing our ability to control dengue vectors. This situation is likely to worsen unless effective strategies are rapidly implemented to mitigate these effects.

Insecticide resistance in dengue vectors

Resistance to cypermethrin of different Aedes aegypti Brazilian populations, collected at two successive periods (2001 and 2002/2003), was monitored using the insecticide-coated bottles bioassay. Slight modifications were included in the method to discriminate between mortality and the knock down effect. Although this pyrethroid was recently started to be used in the country to control the dengue vector, a decrease in susceptibility was noted between both periods analyzed, particularly in the city of Rio de Janeiro. The results indicate that resistance is due at least in part to a target site alteration.

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Gonzalo Efrain Moya

Papers

Monitoring of resistance to the pyrethroid cypermethrin in Brazilian Aedes aegypti (Diptera: Culicidae) populations collected between 2001 and 2003