Permethrin Induction of Multiple Cytochrome P450 Genes in Insecticide Resistant Mosquitoes, Culex quinquefasciatus

Abstract

The expression of some insect P450 genes can be induced by both exogenous and endogenous compounds and there is evidence to suggest that multiple constitutively overexpressed P450 genes are co-responsible for the development of resistance to permethrin in resistant mosquitoes. This study characterized the permethrin induction profiles of P450 genes known to be constitutively overexpressed in resistant mosquitoes, Culex quinquefasciatus. The gene expression in 7 of the 19 P450 genes CYP325K3v1, CYP4D42v2, CYP9J45, (CYP) CPIJ000926, CYP325G4, CYP4C38, CYP4H40 in the HAmCqG8 strain, increased more than 2-fold after exposure to permethrin at an LC50 concentration (10 ppm) compared to their acetone treated counterpart; no significant differences in the expression of these P450 genes in susceptible S-Lab mosquitoes were observed after permethrin treatment. Eleven of the fourteen P450 genes overexpressed in the MAmCqG6 strain, CYP9M10, CYP6Z12, CYP9J33, CYP9J43, CYP9J34, CYP306A1, CYP6Z15, CYP9J45, CYPPAL1, CYP4C52v1, CYP9J39, were also induced more than doubled after exposure to an LC50 (0.7 ppm) dose of permethrin. No significant induction in P450 gene expression was observed in the susceptible S-Lab mosquitoes after permethrin treatment except for CYP6Z15 and CYP9J39, suggesting that permethrin induction of these two P450 genes are common to both susceptible and resistant mosquitoes while the induction of the others are specific to insecticide resistant mosquitoes. These results demonstrate that multiple P450 genes are co-up-regulated in insecticide resistant mosquitoes through both constitutive overexpression and induction mechanisms, providing additional support for their involvement in the detoxification of insecticides and the development of insecticide resistance.

The choreography of the chemical defensome response to insecticide stress: insights into the Anopheles stephensi transcriptome using RNA-Seq

“…However, these are single snapshots of the defense response that do not allow us to know if and how the differentially expressed genes are modulated during toxicant exposure. On the other hand, some studies have investigated the expression profiles of subsets of genes at different time-points during individuals’ exposure to toxicants142223242526. For example, in the mosquito Culex quinquesfasciatus , multiple P450 genes were found co-upregulated in resistant strains during a time course of 12, 24, 48 and 72 hours of permethrin exposure2425.…”

“…On the other hand, some studies have investigated the expression profiles of subsets of genes at different time-points during individuals’ exposure to toxicants142223242526. For example, in the mosquito Culex quinquesfasciatus , multiple P450 genes were found co-upregulated in resistant strains during a time course of 12, 24, 48 and 72 hours of permethrin exposure2425. Likewise, in larvae of a susceptible strain of the mosquito Anopheles stephensi exposed to permethrin, it was analysed the expression pattern of six ABC transporter genes at seven time-points from 30 minutes to 48 hours after exposure.…”

Allelic variants of cytochrome P450 monooxygenases: Constitutive and insecticide-mediated expression in a Malaysian strain of the dengue vector, Aedes aegypti (Diptera: Culicidae)

“…Their effect on insect survival, especially by detoxifying insecticides, makes them prime candidates for insecticide resistance studies, usually revolving around identifying P450s with putative roles in insecticide resistance (Poupardin et al, 2010;Liu et al, 2011;Gong et al, 2013). Though P450s may mediate insecticide resistance in Malaysian A. aegypti (Ishak et al, 2015), neither identifi cation of individual P450s with potential roles in insecticide resistance nor characterization of already identifi ed P450s from other strains under insecticide-induced conditions have been conducted for Malaysian strains.…”

“…Controls were larvae kept in insecticide-free distilled water. There lies (Feyereisen, 2012), with families 4, 6 and 9 usually implicated in insecticide resistance (Amenya et al, 2008;Poupardin et al, 2010;Gong et al, 2013). The induction of P450s by insecticides is an approach commonly used to identify P450 genes potentially involved in mediating insecticide resistance (Poupardin et al, 2010;Feyereisen, 2012).…”

Understanding the Mechanisms Involved in the Regulation of Cytochrome P450 Gene Expression in Drosophila melanogaster (Diptera: Drosophilidae)

“…In the fruit fly, Drosophila melanogaster alone there are 83 P450 genes with a few of these enzymes playing key roles in the metabolism or activation of xenobiotics [3][4][5][6]. These P450s include; Cyp6a2 (substrate-DDT, aldrin, dieldrin and diazinon) [7][8][9] Cyp6g1 (substrate-DDT, imidacloprid) [10,11].…”