Multiple Mechanisms of Permethrin Resistance in the Southern House Mosquito, Culex quinquefasciatus

Abstract

The inherited resistance to permethrin in Culex quinquefasciatus, which is the primary vector of encephalitis and lymphatic filariasis pathogens, resulted from the molecular basis of multiple mechanisms involved in changes of more than one resistant gene. Two major mechanisms of insecticide resistance in mosquito are P450-mediated detoxification via increased the expression level of P450 genes to metabolize the insecticide, and sodium channel insensitivity via modified mutations to change the channel structure and prevent the permethrin binding. In my current studies, I found 4 cytochrome P450 genes were up-regulated and inducible in the resistant mosquito strains indicating the importance of these P450 genes in permethrin resistance, and also synonymous and non-synonymous mutations present in sodium channel as well as multiple sodium channel variances caused the permethrin resistance in Culex mosquitoes. Furthermore, to identify the regulatory pathway of P450 gene expression in insecticide resistance of the Culex mosquito, my studies have revealed, for the first time, that among a total of 120 GPCR signaling-pathway-related genes, 5 of them were significantly up-regulated in the resistant Culex mosquitoes. Functional characterization of the 5 up-regulated-GPCR pathway-related genes in insecticide resistance using the double-stranded RNA-mediated gene interference (RNAi) and Drosophila transgenic techniques have proved that the function of the GPCR-related genes in insecticide resistance by regulating the P450 gene expression through the protein kinase A and AMP-dependent protein kinase pathways. My studies provide new information for the understanding of resistance development at a molecular level and a new avenue for characterizing the regulation pathways in resistance development, and also provide new strategies for control mosquitoes, especially the resistant ones.