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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

Insecticide resistance profile and experimental design of transcriptomic analyses.(a) Resistance profiles to different insecticide classes in female Ae. albopictus mosquitoes across Malaysia including KL (Kuala Lumpur), PG (Penang), JB (Johor Bharu) and KB (Kota Bharu). (b) Schematic representation of the experimental design of the microarray studies for the permethrin resistance profiling whereas (c) is for the comparison between non-exposed (control) vs susceptible samples across Malaysia. Green arrows refer to Cy3 dye, and red arrows refer to Cy5 dye.
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f1: Insecticide resistance profile and experimental design of transcriptomic analyses.(a) Resistance profiles to different insecticide classes in female Ae. albopictus mosquitoes across Malaysia including KL (Kuala Lumpur), PG (Penang), JB (Johor Bharu) and KB (Kota Bharu). (b) Schematic representation of the experimental design of the microarray studies for the permethrin resistance profiling whereas (c) is for the comparison between non-exposed (control) vs susceptible samples across Malaysia. Green arrows refer to Cy3 dye, and red arrows refer to Cy5 dye.

Mentions: The Ae. albopictus populations from Malaysia used in this study were fully susceptible to pyrethroids (both type I and II) except in Kuala Lumpur where a resistance was observed to permethrin and to deltamethrin (87% and 89% mortality respectively) (Fig. 1a). For DDT, a mixed resistance pattern was observed with Kuala Lumpur and Kota Bharu exhibiting high resistance levels (6 and 14% mortality rate respectively) while the Penang population was nearly fully susceptible (96.8% mortality)(Fig. 1a). In contrast, most populations were resistant to bendiocarb except for Kota Bharu (93% mortality). Overall, the KL population was the most resistant as it was also resistant to all insecticide classes including to the organophosphate malathion and to the organochlorine dieldrin (Fig. 1a).


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)

Insecticide resistance profile and experimental design of transcriptomic analyses.(a) Resistance profiles to different insecticide classes in female Ae. albopictus mosquitoes across Malaysia including KL (Kuala Lumpur), PG (Penang), JB (Johor Bharu) and KB (Kota Bharu). (b) Schematic representation of the experimental design of the microarray studies for the permethrin resistance profiling whereas (c) is for the comparison between non-exposed (control) vs susceptible samples across Malaysia. Green arrows refer to Cy3 dye, and red arrows refer to Cy5 dye.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Insecticide resistance profile and experimental design of transcriptomic analyses.(a) Resistance profiles to different insecticide classes in female Ae. albopictus mosquitoes across Malaysia including KL (Kuala Lumpur), PG (Penang), JB (Johor Bharu) and KB (Kota Bharu). (b) Schematic representation of the experimental design of the microarray studies for the permethrin resistance profiling whereas (c) is for the comparison between non-exposed (control) vs susceptible samples across Malaysia. Green arrows refer to Cy3 dye, and red arrows refer to Cy5 dye.
Mentions: The Ae. albopictus populations from Malaysia used in this study were fully susceptible to pyrethroids (both type I and II) except in Kuala Lumpur where a resistance was observed to permethrin and to deltamethrin (87% and 89% mortality respectively) (Fig. 1a). For DDT, a mixed resistance pattern was observed with Kuala Lumpur and Kota Bharu exhibiting high resistance levels (6 and 14% mortality rate respectively) while the Penang population was nearly fully susceptible (96.8% mortality)(Fig. 1a). In contrast, most populations were resistant to bendiocarb except for Kota Bharu (93% mortality). Overall, the KL population was the most resistant as it was also resistant to all insecticide classes including to the organophosphate malathion and to the organochlorine dieldrin (Fig. 1a).

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