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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

Haplotypic association tests for the threekdrhaplotypes (1014L-1575N,1014F-1575Nand1014 F-1575Y) with survival of VK7An. coluzzito deltamethrin LT50. Odds ratios (OR) are represented with the level of significance and the arrows within the triangles show the direction of the OR calculation. *p < 0.05, **p < 0.01.
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Fig5: Haplotypic association tests for the threekdrhaplotypes (1014L-1575N,1014F-1575Nand1014 F-1575Y) with survival of VK7An. coluzzito deltamethrin LT50. Odds ratios (OR) are represented with the level of significance and the arrows within the triangles show the direction of the OR calculation. *p < 0.05, **p < 0.01.

Mentions: In almost all cases the frequencies of 1014F and 1575Y were higher in mosquitoes surviving insecticide exposure but the presence of the 1014F allele was only significantly associated with deltamethrin survival in one round (October 2011) (P = 0.04) and in the case of 1575Y, an association with deltamethrin survival was observed in two rounds of collection (P = 0.015 and 0.043 in October 2011 and June 2012 respectively (Table 1)). 1575Y occurs exclusively on a haplotypic background of 1014F and a stronger association of the haplotype, rather than single alleles, has been demonstrated for DDT and pyrethroid resistance in some cases [19]. Haplotypic association tests revealed that the presence of both 1014F and 1575Y alleles increased the OR of surviving the deltamethrin LT50 in VK7 from all three collection rounds but the difference was only significant for samples collected in October 2011 and in June 2012 (OR 2.68 (P = 0.007) and 3.00 (P = 0.046) respectively (Figure 5)).Figure 5


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)

Haplotypic association tests for the threekdrhaplotypes (1014L-1575N,1014F-1575Nand1014 F-1575Y) with survival of VK7An. coluzzito deltamethrin LT50. Odds ratios (OR) are represented with the level of significance and the arrows within the triangles show the direction of the OR calculation. *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Haplotypic association tests for the threekdrhaplotypes (1014L-1575N,1014F-1575Nand1014 F-1575Y) with survival of VK7An. coluzzito deltamethrin LT50. Odds ratios (OR) are represented with the level of significance and the arrows within the triangles show the direction of the OR calculation. *p < 0.05, **p < 0.01.
Mentions: In almost all cases the frequencies of 1014F and 1575Y were higher in mosquitoes surviving insecticide exposure but the presence of the 1014F allele was only significantly associated with deltamethrin survival in one round (October 2011) (P = 0.04) and in the case of 1575Y, an association with deltamethrin survival was observed in two rounds of collection (P = 0.015 and 0.043 in October 2011 and June 2012 respectively (Table 1)). 1575Y occurs exclusively on a haplotypic background of 1014F and a stronger association of the haplotype, rather than single alleles, has been demonstrated for DDT and pyrethroid resistance in some cases [19]. Haplotypic association tests revealed that the presence of both 1014F and 1575Y alleles increased the OR of surviving the deltamethrin LT50 in VK7 from all three collection rounds but the difference was only significant for samples collected in October 2011 and in June 2012 (OR 2.68 (P = 0.007) and 3.00 (P = 0.046) respectively (Figure 5)).Figure 5

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