Limits...
The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

Ishak IH, Riveron JM, Ibrahim SS, Stott R, Longbottom J, Irving H, Wondji CS - Sci Rep (2016)

Bottom Line: Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance.CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations.The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

View Article: PubMed Central - PubMed

Affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom.

ABSTRACT
Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

No MeSH data available.


Related in: MedlinePlus

Knockdown and mortality rate after bioassay tests with transgenic strains for CYP6P12 at different time-points.(a) is the result for test with deltamethrin on the transgenic Act5C-CYP6P12 strain and the control strain (the progeny from the cross between the UAS-CYP6P12 females and w1118 males (which do not over-express the P450 transgene). (b) is the result for permethrin on transgenic Act5C-CYP6P12; (c) is the result for bifenthrin on transgenic Act5C-CYP6P12 and (d) is for etofenprox on transgenic Act5C-CYP6P12.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4837359&req=5

f3: Knockdown and mortality rate after bioassay tests with transgenic strains for CYP6P12 at different time-points.(a) is the result for test with deltamethrin on the transgenic Act5C-CYP6P12 strain and the control strain (the progeny from the cross between the UAS-CYP6P12 females and w1118 males (which do not over-express the P450 transgene). (b) is the result for permethrin on transgenic Act5C-CYP6P12; (c) is the result for bifenthrin on transgenic Act5C-CYP6P12 and (d) is for etofenprox on transgenic Act5C-CYP6P12.

Mentions: To confirm that the over-transcription of CYP6P12 alone can confer pyrethroid resistance, transgenic D. melanogaster expressing a CYP6P12 allele from KL (Figure S2) under the control of the ubiquitous Act5C-GAL4 driver were successfully generated. Contact bioassays performed with 0.15% deltamethrin (Type II pyrethroid) revealed that transgenic flies over-expressing CYP6P12 were resistant to deltamethrin with significantly reduced mortality/knockdown rates observed at four different exposure times compared with the control group not expressing CYP6P12. These exposure times are 1 h (2.5 vs. 35.5%, P = 0.0004), 2 h (2.5 vs. 77%, P < 0.0001), 3 h (5.8 vs. 87.5%, P < 0.0001) and 6 h (16.8 vs. 87.5%, P < 0.0001) (Fig. 3a; Table S6). This results demonstrate that over-transcription of CYP6P12 alone is sufficient to confer resistance to deltamethrin.


The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus.

Ishak IH, Riveron JM, Ibrahim SS, Stott R, Longbottom J, Irving H, Wondji CS - Sci Rep (2016)

Knockdown and mortality rate after bioassay tests with transgenic strains for CYP6P12 at different time-points.(a) is the result for test with deltamethrin on the transgenic Act5C-CYP6P12 strain and the control strain (the progeny from the cross between the UAS-CYP6P12 females and w1118 males (which do not over-express the P450 transgene). (b) is the result for permethrin on transgenic Act5C-CYP6P12; (c) is the result for bifenthrin on transgenic Act5C-CYP6P12 and (d) is for etofenprox on transgenic Act5C-CYP6P12.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837359&req=5

f3: Knockdown and mortality rate after bioassay tests with transgenic strains for CYP6P12 at different time-points.(a) is the result for test with deltamethrin on the transgenic Act5C-CYP6P12 strain and the control strain (the progeny from the cross between the UAS-CYP6P12 females and w1118 males (which do not over-express the P450 transgene). (b) is the result for permethrin on transgenic Act5C-CYP6P12; (c) is the result for bifenthrin on transgenic Act5C-CYP6P12 and (d) is for etofenprox on transgenic Act5C-CYP6P12.
Mentions: To confirm that the over-transcription of CYP6P12 alone can confer pyrethroid resistance, transgenic D. melanogaster expressing a CYP6P12 allele from KL (Figure S2) under the control of the ubiquitous Act5C-GAL4 driver were successfully generated. Contact bioassays performed with 0.15% deltamethrin (Type II pyrethroid) revealed that transgenic flies over-expressing CYP6P12 were resistant to deltamethrin with significantly reduced mortality/knockdown rates observed at four different exposure times compared with the control group not expressing CYP6P12. These exposure times are 1 h (2.5 vs. 35.5%, P = 0.0004), 2 h (2.5 vs. 77%, P < 0.0001), 3 h (5.8 vs. 87.5%, P < 0.0001) and 6 h (16.8 vs. 87.5%, P < 0.0001) (Fig. 3a; Table S6). This results demonstrate that over-transcription of CYP6P12 alone is sufficient to confer resistance to deltamethrin.

Bottom Line: Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance.CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations.The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

View Article: PubMed Central - PubMed

Affiliation: Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom.

ABSTRACT
Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

No MeSH data available.


Related in: MedlinePlus