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Gene Amplification, ABC Transporters and Cytochrome P450s: Unraveling the Molecular Basis of Pyrethroid Resistance in the Dengue Vector, Aedes aegypti

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Bariami, Vassiliki, Jones, Christopher, Poupardin, Rodolphe, Vontas, John and Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247 (2012) 'Gene Amplification, ABC Transporters and Cytochrome P450s: Unraveling the Molecular Basis of Pyrethroid Resistance in the Dengue Vector, Aedes aegypti'. PLoS Neglected Tropical Diseases, Vol 6, Issue 6, e1692.

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Abstract

Background

Pyrethroid insecticides are widely utilized in dengue control. However, the major vector, Aedes aegypti, is becoming increasingly resistant to these insecticides and this is impacting on the efficacy of control measures. The near complete transcriptome of two pyrethroid resistant populations from the Caribbean was examined to explore the molecular basis of this resistance.

Principal Findings

Two previously described target site mutations, 1016I and 1534C were detected in pyrethroid resistant populations from Grand Cayman and Cuba. In addition between two and five per cent of the Ae. aegypti transcriptome was differentially expressed in the resistant populations compared to a laboratory susceptible population. Approximately 20 per cent of the genes over-expressed in resistant mosquitoes were up-regulated in both Caribbean populations (107 genes). Genes with putative monooxygenase activity were significantly over represented in the up-regulated subset, including five CYP9 P450 genes. Quantitative PCR was used to confirm the higher transcript levels of multiple cytochrome P450 genes from the CYP9J family and an ATP binding cassette transporter. Over expression of two genes, CYP9J26 and ABCB4, is due, at least in part, to gene amplification.

Significance

These results, and those from other studies, strongly suggest that increases in the amount of the CYP9J cytochrome P450s are an important mechanism of pyrethroid resistance in Ae. aegypti. The genetic redundancy resulting from the expansion of this gene family makes it unlikely that a single gene or mutation responsible for pyrethroid resistance will be identified in this mosquito species. However, the results from this study do pave the way for the development of new pyrethroid synergists and improved resistance diagnostics. The role of copy number polymorphisms in detoxification and transporter genes in providing protection against insecticide exposure requires further investigation.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 470 Genetic structures
QX Parasitology > Insects. Other Parasites > QX 525 Aedes
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
WC Communicable Diseases > Virus Diseases > Infectious Mononucleosis. Arbovirus Infections > WC 528 Dengue
Faculty: Department: Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0001692
Depositing User: Users 183 not found.
Date Deposited: 18 Jun 2012 10:56
Last Modified: 30 Aug 2019 17:05
URI: https://archive.lstmed.ac.uk/id/eprint/2858

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