Expression Profile of Genes during Resistance Reversal in a Temephos Selected Strain of the Dengue Vector, Aedes aegypti

Clare Strode, Maria de Melo-Santos, Tereza Magalhães, Ana Araújo, Contancia Ayres

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: The mosquito Aedes aegypti is one of the most important disease vectors because it transmits two major arboviruses, dengue and yellow fever, which cause significant global morbidity and mortality. Chemical insecticides form the cornerstone of vector control. The organophosphate temephos a larvicide recommended by WHO for controlling Ae. aegypti, however, resistance to this compound has been reported in many countries, including Brazil. Methodology/Principal Findings: The aim of this study was to identify genes implicated in metabolic resistance in an Ae. aegypti temephos resistant strain, named RecR, through microarray analysis. We utilized a custom ‘Ae. aegypti detox chip’ and validated microarray data through RT-PCR comparing susceptible and resistant individuals. In addition, we analyzed gene expression in 4th instar larvae from a reversed susceptible strain (RecRev), exposed and unexposed to temephos. The results obtained revealed a set of 13 and 6 genes significantly over expressed in resistant adult mosquitoes and larvae, respectively. One of these genes, the cytochrome P450 CYP6N12, was up-regulated in both stages. RT-PCR confirmed the microarray results and, additionally, showed no difference in gene expression between temephos exposed and unexposed RecRev mosquitoes. This suggested that the differences in the transcript profiles among the strains are heritable due to a selection process and are not caused by immediate insecticide exposure. Reversal of temephos resistance was demonstrated and, importantly, there was a positive correlation between a decrease in the resistance ratio and an accompanying decrease in the expression levels of previously over expressed genes. Some of the genes identified here have also been implicated in metabolic resistance in other mosquito species and insecticide resistant populations of Ae. aegypti. Conclusions/Significance: The identification of gene expression signatures associated to insecticide resistance and their suppression could greatly aid the development of improved strategies of vector control.
Original languageEnglish
Pages (from-to)1-8
JournalPLoS ONE
Volume7
Issue number8
DOIs
Publication statusPublished - 2012

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Temefos
temephos
dengue
Dengue
Aedes
Aedes aegypti
Transcriptome
Insecticides
Culicidae
Genes
Microarrays
Gene expression
insecticides
vector control
genes
gene expression
Larva
Yellow fever virus
reverse transcriptase polymerase chain reaction
Insecticide Resistance

Cite this

Strode, Clare ; de Melo-Santos, Maria ; Magalhães, Tereza ; Araújo, Ana ; Ayres, Contancia. / Expression Profile of Genes during Resistance Reversal in a Temephos Selected Strain of the Dengue Vector, Aedes aegypti. In: PLoS ONE. 2012 ; Vol. 7, No. 8. pp. 1-8.
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Expression Profile of Genes during Resistance Reversal in a Temephos Selected Strain of the Dengue Vector, Aedes aegypti. / Strode, Clare; de Melo-Santos, Maria; Magalhães, Tereza; Araújo, Ana; Ayres, Contancia.

In: PLoS ONE, Vol. 7, No. 8, 2012, p. 1-8.

Research output: Contribution to journalArticle

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N2 - Background: The mosquito Aedes aegypti is one of the most important disease vectors because it transmits two major arboviruses, dengue and yellow fever, which cause significant global morbidity and mortality. Chemical insecticides form the cornerstone of vector control. The organophosphate temephos a larvicide recommended by WHO for controlling Ae. aegypti, however, resistance to this compound has been reported in many countries, including Brazil. Methodology/Principal Findings: The aim of this study was to identify genes implicated in metabolic resistance in an Ae. aegypti temephos resistant strain, named RecR, through microarray analysis. We utilized a custom ‘Ae. aegypti detox chip’ and validated microarray data through RT-PCR comparing susceptible and resistant individuals. In addition, we analyzed gene expression in 4th instar larvae from a reversed susceptible strain (RecRev), exposed and unexposed to temephos. The results obtained revealed a set of 13 and 6 genes significantly over expressed in resistant adult mosquitoes and larvae, respectively. One of these genes, the cytochrome P450 CYP6N12, was up-regulated in both stages. RT-PCR confirmed the microarray results and, additionally, showed no difference in gene expression between temephos exposed and unexposed RecRev mosquitoes. This suggested that the differences in the transcript profiles among the strains are heritable due to a selection process and are not caused by immediate insecticide exposure. Reversal of temephos resistance was demonstrated and, importantly, there was a positive correlation between a decrease in the resistance ratio and an accompanying decrease in the expression levels of previously over expressed genes. Some of the genes identified here have also been implicated in metabolic resistance in other mosquito species and insecticide resistant populations of Ae. aegypti. Conclusions/Significance: The identification of gene expression signatures associated to insecticide resistance and their suppression could greatly aid the development of improved strategies of vector control.

AB - Background: The mosquito Aedes aegypti is one of the most important disease vectors because it transmits two major arboviruses, dengue and yellow fever, which cause significant global morbidity and mortality. Chemical insecticides form the cornerstone of vector control. The organophosphate temephos a larvicide recommended by WHO for controlling Ae. aegypti, however, resistance to this compound has been reported in many countries, including Brazil. Methodology/Principal Findings: The aim of this study was to identify genes implicated in metabolic resistance in an Ae. aegypti temephos resistant strain, named RecR, through microarray analysis. We utilized a custom ‘Ae. aegypti detox chip’ and validated microarray data through RT-PCR comparing susceptible and resistant individuals. In addition, we analyzed gene expression in 4th instar larvae from a reversed susceptible strain (RecRev), exposed and unexposed to temephos. The results obtained revealed a set of 13 and 6 genes significantly over expressed in resistant adult mosquitoes and larvae, respectively. One of these genes, the cytochrome P450 CYP6N12, was up-regulated in both stages. RT-PCR confirmed the microarray results and, additionally, showed no difference in gene expression between temephos exposed and unexposed RecRev mosquitoes. This suggested that the differences in the transcript profiles among the strains are heritable due to a selection process and are not caused by immediate insecticide exposure. Reversal of temephos resistance was demonstrated and, importantly, there was a positive correlation between a decrease in the resistance ratio and an accompanying decrease in the expression levels of previously over expressed genes. Some of the genes identified here have also been implicated in metabolic resistance in other mosquito species and insecticide resistant populations of Ae. aegypti. Conclusions/Significance: The identification of gene expression signatures associated to insecticide resistance and their suppression could greatly aid the development of improved strategies of vector control.

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