Dataset Information

Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes.

ABSTRACT:

Background

Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance.

Methodology/principal findings

Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ? 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.

Conclusion/significance

The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.

SUBMITTER: Ishak IH

PROVIDER: S-EPMC5289618 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes.

Ishak Intan H IH Kamgang Basile B Ibrahim Sulaiman S SS Riveron Jacob M JM Irving Helen H Wondji Charles S CS

PLoS neglected tropical diseases 20170123 1

<h4>Background</h4>Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti popula ...[more]

PMID: 28114328

Similar Datasets

Project description:Dengue is the most prevalent arboviral disease world-wide and its primary vector is the mosquito Aedes aegypti. The current lack of commercially-available vaccines makes control of vector populations the only effective strategy to prevent dengue transmission. Aedes aegypti geographic populations exhibit great variability in insecticide resistance and susceptibility to dengue infection. The characterization of single nucleotide polymorphisms (SNPs) as molecular markers to study quantitatively this variation is needed greatly because this species has a low abundance of microsatellite markers and limited known restriction fragments length polymorphisms (RFLPs) and single-strand conformation polymorphism (SSCP) markers.We used RNA-seq to characterize SNPs in three Ae. aegypti strains, including the Liverpool (LVP) strain, from which the current genome annotation is derived. We identified 131,764 unique genome locations with at least one alternative nucleotide to what is reported in the reference annotation. These comprised changes in both open-reading frames (ORFs) and untranslated regions (UTRs) of transcripts. An in depth-look at sequence variation in immunity genes revealed that those associated with autophagy, MD2-like receptors and Peptidoglycan Recognition Proteins had more sequence variation in their 3'UTRs than mutations associated with non-synonymous changes. This supports the conclusion that these genes had maintained their functional specificity while being adapted to different regulatory domains. In contrast, a number of peroxidases, serpins and Clip-domain serine proteases exhibited conservation of putative UTR regulatory sequences while displaying diversification of the ORFs. Transcriptome evidence also was found for ~2500 novel transcriptional units (NTUs) not annotated in the reference genome.The transcriptome-wide assessment of within and inter-strain polymorphisms in Ae. aegypti adds considerably to the number of molecular markers available for genetic studies in this mosquito. Additionally, data supporting NTU discovery emphasizes the need for continuous amendments of the reference genome annotation.

Dataset Information

Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes.

Background

Methodology/principal findings

Conclusion/significance

Publications

Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes.

Similar Datasets

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