Data from: Genetic mapping identifies a major locus spanning P450 clusters associated with pyrethroid resistance in kdr-free Anopheles arabiensis from Chad

Prevention of malaria transmission throughout much of Africa is dependent on bednets that are impregnated with pyrethroid insecticides. Anopheles arabiensis is the major malaria vector in Chad and efforts to control this vector are threatened by the emergence of pyrethroid resistance. WHO bioassays revealed that An. arabiensis from Ndjamena is resistant to pyrethroids and dichlorodiphenyltrichloroethane (DDT) but fully susceptible to carbamates and organophosphates. No 1014F or 1014S kdr alleles were detected in this population. To determine the mechanisms that are responsible for resistance, genetic crosses were established between the Ndja strain and an insecticide susceptible population from Mozambique. Resistance was inherited as an autosomal trait and quantitative trait locus (QTL) mapping identified a single major locus on chromosome 2R, which explained 24.4% of the variance in resistance. This QTL is enriched in P450 genes including 25 cytochrome P450s in total. One of these, Cyp6p4 is 22-fold upregulated in the Ndja strain compared with the susceptible. Piperonyl butoxide (PBO) synergist and biochemical assays further support a role for P450s in conferring pyrethroid resistance in this population.

在非洲大部分地区，疟疾传播的防控主要依赖于涂抹有拟除虫菊酯类杀虫剂的蚊帐。阿拉伯按蚊（Anopheles arabiensis）是乍得地区主要的疟疾传播媒介，而拟除虫菊酯抗性的出现正对该媒介的防控工作构成威胁。世界卫生组织（WHO）生物测定实验显示，来自恩贾梅纳的阿拉伯按蚊对拟除虫菊酯与二氯二苯基三氯乙烷（DDT）具有抗性，但对氨基甲酸酯类与有机磷酸酯类药剂完全敏感。该种群未检测到1014F或1014S型击倒抗性（kdr）等位基因。为明确该抗性的产生机制，研究人员以恩贾梅纳株（Ndja strain）与来自莫桑比克的杀虫剂敏感种群开展了杂交实验。抗性以常染色体性状的方式遗传，通过数量性状位点（QTL）定位分析，研究人员在2号染色体右臂（2R）上鉴定出一个主效位点，该位点可解释24.4%的抗性表型变异。该QTL区域富集了细胞色素P450基因，共计包含25个细胞色素P450基因。其中，Cyp6p4基因在恩贾梅纳株中的表达量较敏感株上调了22倍。胡椒基丁醚（PBO）增效剂实验与生化测定结果进一步证实，细胞色素P450介导了该种群对拟除虫菊酯的抗性。