Toé Kobié H, N'Falé Sagnon, Dabiré Roch K, Ranson Hilary, Jones Christopher M
Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Centre National de Recherche et de la Formation sur le Paludisme, Ouagadougou, 01BP 2208, Burkina Faso.
BMC Genomics. 2015 Mar 1;16(1):146. doi: 10.1186/s12864-015-1342-6.
Since 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012.
Mosquitoes were collected from south-west Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were compared to laboratory susceptible colonies using whole-genome microarrays. Using a stringent filtering process we identified 136 genes, including the well-studied detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification genes (e.g. cell transporters and cuticular components), associated with pyrethroid resistance, whose basal expression level increased during the timeframe of the study. A subset of these were validated by qPCR using samples from two study sites, collected over 3 years and marked increases in expression were observed each year. We hypothesise that these genes are contributing to this rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed that the majority of the resistance phenotype is not explained by target-site modifications.
Our data indicate that the recent and rapid increase in pyrethroid resistance observed in south-west Burkina Faso is associated with gene expression profiles described here. Over a third of these candidates are also overexpressed in multiple pyrethroid resistant populations of An. coluzzi from neighbouring Côte d'Ivoire. This suite of molecular markers can be used to track the spread of the extreme pyrethroid resistance phenotype that is sweeping through West Africa and to determine the functional basis of this trait.
自2011年以来，布基纳法索主要疟疾媒介科氏疟蚊对拟除虫菊酯的抗性水平已升至如此程度，以至于该国目前使用的所有长效驱虫蚊帐（LLINs）均无法杀死当地的蚊虫媒介。我们利用2011年和2012年进行的两项独立的全基因组微阵列研究，调查了这种观察到的抗性增加是否与野外捕获的科氏疟蚊的转录变化有关。
2011年和2012年从布基纳法索西南部采集蚊子，并使用全基因组微阵列将接触或未接触杀虫剂的昆虫与实验室易感群体进行比较。通过严格的筛选过程，我们鉴定出136个与拟除虫菊酯抗性相关的基因，包括研究充分的解毒酶（细胞色素P450单加氧酶和酯酶）和非解毒基因（如细胞转运蛋白和表皮成分），其基础表达水平在研究期间有所增加。其中一部分通过qPCR使用来自两个研究地点、在3年期间收集的样本进行了验证，并且每年都观察到表达的显著增加。我们假设这些基因促成了科氏疟蚊中这种迅速增加的抗性表型。对击倒抗性（kdr）突变（L1014S、L1014F和N1575Y）的全面分析表明，大多数抗性表型无法用靶位点修饰来解释。
我们的数据表明，布基纳法索西南部近期观察到的拟除虫菊酯抗性的迅速增加与此处描述的基因表达谱有关。这些候选基因中有超过三分之一在来自邻国科特迪瓦的多个对拟除虫菊酯具有抗性的科氏疟蚊群体中也过度表达。这套分子标记可用于追踪正在席卷西非的极端拟除虫菊酯抗性表型的传播，并确定该性状的功能基础。
