Relationship between knockdown resistance, metabolic detoxification and organismal resistance to pyrethroids in Anopheles sinensis.

Daibin Zhong,Zhengbo He,Mariangela Bonizzoni,Mei-Hui Wang,Bin Zheng,Zhentian Yan,Tielong Xu,Liwang Cui,Bin Chen,Guiyun Yan,Fengyang Fu,Guofa Zhou,Guoding Zhu,Xuelian Chang

doi:10.1371/journal.pone.0055475

Abstract

Anopheles sinensis is the most important vector of malaria in Southeast Asia, including China. Currently, the most effective measure to prevent malaria transmission relies on vector control through the use of insecticides, primarily pyrethroids. Extensive use of insecticides poses strong selection pressure on mosquito populations for resistance. Resistance to insecticides can arise due to mutations in the insecticide target site (target site resistance), which in the case of pyrethroids is the para-type sodium channel gene, and/or the catabolism of the insecticide by detoxification enzymes before it reaches its target (metabolic detoxification resistance). In this study, we examined deltamethrin resistance in An. sinensis from China and investigated the relative importance of target site versus metabolic detoxification mechanisms in resistance. A high frequency (>85%) of nonsynonymous mutations in the para gene was found in populations from central China, but not in populations from southern China. Metabolic detoxification as measured by the activity of monooxygenases and glutathione S-transferases (GSTs) was detected in populations from both central and southern China. Monooxygenase activity levels were significantly higher in the resistant than the susceptible mosquitoes, independently of their geographic origin. Stepwise multiple regression analyses in mosquito populations from central China found that both knockdown resistance (kdr) mutations and monooxygenase activity were significantly associated with deltamethrin resistance, with monooxygenase activity playing a stronger role. These results demonstrate the importance of metabolic detoxification in pyrethroid resistance in An. sinensis, and suggest that different mechanisms of resistance could evolve in geographically different populations.

Highlights

The mosquito Anopheles sinensis is the major malaria vector in China and other Southeast Asian countries [1,2,3,4,5,6]
This study examined phenotypic resistance to deltamethrin in An. sinensis from China in relation to mutations in the insecticide target site and levels of detoxification enzymes
When target site mutations and levels of detoxification enzymes were tested in phenotypically- resistant and -susceptible mosquitoes, major differences were found between the populations from southern and central China

Summary

Introduction

The mosquito Anopheles sinensis is the major malaria vector in China and other Southeast Asian countries [1,2,3,4,5,6]. The World Health Organization (WHO) defines vector control as one of the four basic and most effective measures to prevent malaria transmission. Vector control relies primarily on the use of insecticides through insecticide-impregnated bednets and indoor residual spray [7]. Permethrin and deltamethrin, are widely used for malaria vector control worldwide [12,13], where the use of impregnated bednets has been shown to be very effective in reducing malaria transmission [14,15]. In China, extensive use of insecticides for agricultural pest and public health disease vector control has posed intensive selection pressure on mosquitoes [12,16]. High levels of resistance to deltamethrin have been reported in An. sinensis populations from China and Korea [12,17]

Methods

Results

Conclusion