title: Relationship between knockdown resistance, metabolic detoxification and organismal resistance to pyrethroids in Anopheles sinensis.
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.
authors: Program in Public Health, College of Health Sciences, University of California Irvine, Irvine, CA, USA.
authors: Daibin
authors: D
authors: Zhong
authors: Xuelian
authors: X
authors: Chang
authors: Guofa
authors: G
authors: Zhou
authors: Zhengbo
authors: Z
authors: He
authors: Fengyang
authors: F
authors: Fu
authors: Zhentian
authors: Z
authors: Yan
authors: Guoding
authors: G
authors: Zhu
authors: Tielong
authors: T
authors: Xu
authors: Mariangela
authors: M
authors: Bonizzoni
authors: Mei-Hui
authors: MH
authors: Wang
authors: Liwang
authors: L
authors: Cui
authors: Bin
authors: B
authors: Zheng
authors: Bin
authors: B
authors: Chen
authors: Guiyun
authors: G
authors: Yan
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D002681:China; D009033:Culicidae / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D008658:Inactivation, Metabolic / Q000235:genetics*; D007303:Insect Vectors / Q000235:genetics; D007305:Insecticide Resistance / Q000187:drug effects / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009032:Mosquito Control / Q000379:methods; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D006899:Mixed Function Oxygenases; D005982:Glutathione Transferase