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The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi in West Africa is linked to increased expression of multiple gene families.

Toé KH, N'Falé S, Dabiré RK, Ranson H, Jones CM - BMC Genomics (2015)

Bottom Line: Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here.Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire.This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.

View Article: PubMed Central - PubMed

Affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK. H.Toe@liverpool.ac.uk.

ABSTRACT

Background: Since 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012.

Results: Mosquitoes were collected from south-west Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were compared to laboratory susceptible colonies using whole-genome microarrays. Using a stringent filtering process we identified 136 genes, including the well-studied detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification genes (e.g. cell transporters and cuticular components), associated with pyrethroid resistance, whose basal expression level increased during the timeframe of the study. A subset of these were validated by qPCR using samples from two study sites, collected over 3 years and marked increases in expression were observed each year. We hypothesise that these genes are contributing to this rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed that the majority of the resistance phenotype is not explained by target-site modifications.

Conclusions: Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here. Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire. This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.

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Related in: MedlinePlus

Hierarchial clustering analysis of the candidate probes for deltamethrin resistance over-expressed inAn. coluzzifrom VK7. Clustering was performed using the Euclidean distance method on the 157 probes which were over-expressed in VK7 versus MAL in 2011 and 2012 as well as those over-expressed against NG. The colour scale represents the log fold change of VK7 against the susceptible strain.
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Fig4: Hierarchial clustering analysis of the candidate probes for deltamethrin resistance over-expressed inAn. coluzzifrom VK7. Clustering was performed using the Euclidean distance method on the 157 probes which were over-expressed in VK7 versus MAL in 2011 and 2012 as well as those over-expressed against NG. The colour scale represents the log fold change of VK7 against the susceptible strain.

Mentions: We included An. coluzzi mosquitoes from Tengrela (TEN) in the 2012 experiment to see whether a common set of genes were up-regulated in pyrethroid resistant mosquitoes from VK7 and TEN. Considering that resistance is higher in VK7 than TEN, we only retained probes significantly over-expressed in VK7 compared to TEN. This gave a final candidate gene list containing 157 probes (Additional file 3). A hierarchical clustering analysis based on the expression profiles of three comparisons between VK7/MAL (2011), VK7/MAL (2012) and VK7/NG (2012) is presented in Figure 4. If putative alternative transcripts of the same gene and duplicate probes are removed, the candidate gene list reduces further to 136 unique genes. Several of the detoxification genes having higher FC in 2012, including CYP4G16, CYP9J5, CYP9M1, COEAE3G, GSTE5, were retained in this list as well the components of the cuticle (e.g. CPR 73, CPAPA3-A1a and CPAPA3-A1b) and the chymotrypsin-1, aquaporin and ATP synthase (Additional file 3).Figure 4


The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi in West Africa is linked to increased expression of multiple gene families.

Toé KH, N'Falé S, Dabiré RK, Ranson H, Jones CM - BMC Genomics (2015)

Hierarchial clustering analysis of the candidate probes for deltamethrin resistance over-expressed inAn. coluzzifrom VK7. Clustering was performed using the Euclidean distance method on the 157 probes which were over-expressed in VK7 versus MAL in 2011 and 2012 as well as those over-expressed against NG. The colour scale represents the log fold change of VK7 against the susceptible strain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352231&req=5

Fig4: Hierarchial clustering analysis of the candidate probes for deltamethrin resistance over-expressed inAn. coluzzifrom VK7. Clustering was performed using the Euclidean distance method on the 157 probes which were over-expressed in VK7 versus MAL in 2011 and 2012 as well as those over-expressed against NG. The colour scale represents the log fold change of VK7 against the susceptible strain.
Mentions: We included An. coluzzi mosquitoes from Tengrela (TEN) in the 2012 experiment to see whether a common set of genes were up-regulated in pyrethroid resistant mosquitoes from VK7 and TEN. Considering that resistance is higher in VK7 than TEN, we only retained probes significantly over-expressed in VK7 compared to TEN. This gave a final candidate gene list containing 157 probes (Additional file 3). A hierarchical clustering analysis based on the expression profiles of three comparisons between VK7/MAL (2011), VK7/MAL (2012) and VK7/NG (2012) is presented in Figure 4. If putative alternative transcripts of the same gene and duplicate probes are removed, the candidate gene list reduces further to 136 unique genes. Several of the detoxification genes having higher FC in 2012, including CYP4G16, CYP9J5, CYP9M1, COEAE3G, GSTE5, were retained in this list as well the components of the cuticle (e.g. CPR 73, CPAPA3-A1a and CPAPA3-A1b) and the chymotrypsin-1, aquaporin and ATP synthase (Additional file 3).Figure 4

Bottom Line: Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here.Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire.This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.

View Article: PubMed Central - PubMed

Affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK. H.Toe@liverpool.ac.uk.

ABSTRACT

Background: Since 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012.

Results: Mosquitoes were collected from south-west Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were compared to laboratory susceptible colonies using whole-genome microarrays. Using a stringent filtering process we identified 136 genes, including the well-studied detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification genes (e.g. cell transporters and cuticular components), associated with pyrethroid resistance, whose basal expression level increased during the timeframe of the study. A subset of these were validated by qPCR using samples from two study sites, collected over 3 years and marked increases in expression were observed each year. We hypothesise that these genes are contributing to this rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed that the majority of the resistance phenotype is not explained by target-site modifications.

Conclusions: Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here. Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire. This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.

Show MeSH
Related in: MedlinePlus