Identification of the pyrethroid resistance mutation on chromosome 1 in Aedes aegypti

摘要/摘要： 在这里，我们试图了解伊蚊对拟除虫菊酯杀虫剂抗药性的演变。 埃及伊蚊是登革热和寨卡病毒等人类疾病的重要传播媒介。拟除虫菊酯类杀虫剂 广泛用于控制成年伊蚊，但在许多种群中已经进化出抗药性， 这对控制这种媒介及其传播的疾病是一个全球性的挑战。查找 延缓蚊媒对少数可用蚊子产生抗药性的策略 杀虫剂是至关重要的。要做到这一点，识别导致耐药性的突变是至关重要的。 为了设计敏感和精确的监测计划，了解人口 遗传学和抗性的进化，并设计有效的对策来减缓 抗药性的发展。 我们的长期目标是开发必要的技术来监测抗性等位基因，以便 可以研究这一重要的进化过程，以便抗药性的发展 延迟了。我们的短期目标是确定导致新发现的 埃及斑潜蝇1号染色体上的拟除虫菊酯抗性基因。为了实现我们的短期目标，我们将 追求两个具体目标： 目的1.高分辨率测定1号染色体上的抗性基因。 目的2.对1号染色体和2号染色体上抗性基因的候选基因进行评估 对引起抗药性的突变进行验证。 已经获得了大量的初步数据来支持这一提议。除了……之外 敏感岩石和特性良好的SP菌株，我们分离到两个同源抗性 菌株。CKR品系含有从SP品系导入的抗性因子 岩石菌株的背景，而KR菌株的背景中只包含kdr突变 摇滚乐。我们还对这些基因进行了转录(RNAseq)和蛋白质组学分析 这将有助于我们在抗性基因座上选择候选基因。 这些实验将使我们能够在埃及伊蚊中鉴定出一种新的拟除虫菊酯抗性突变。 将为我们提供有关埃及伊蚊在其他种群中发生频率的初步信息 环球网。这些数据将提供有关以下方面的相似性和差异性的新信息 杀虫剂的选择对地理上相距遥远的种群产生了影响。我们的结果将构成基础 未来对这一重要媒介的抗性监测和抗性管理的研究 人类疾病。

SUMMARY/ABSTRACT: Here we seek to understand the evolution of resistance to pyrethroid insecticides in Aedes aegypti, an important vector of human diseases such as dengue and Zika. Pyrethroid insecticides are widely used for control of adult Aedes, but resistance has evolved in many populations, representing a global challenge for control of this vector and the diseases it transmits. Finding strategies for delaying the development of resistance by mosquito vectors to the few available insecticides is critical. To do so, it is essential to identify the mutations responsible for resistance in order to design sensitive and precise monitoring programs, to understand the population genetics and the evolution of resistance, and to design effective countermeasures to slow the development of resistance. Our long-term goal is to develop the necessary technologies for monitoring resistance alleles so that this important evolutionary process can be studied and so that the development of resistance can be delayed. Our short-term goal is to determine the mutation responsible for the newly identified pyrethroid resistance locus on chromosome 1 in A. aegypti. To address our short-term goal, we will pursue two specific aims: Aim 1. Determining the resistance locus on chromosome 1 with high resolution. Aim 2. Evaluation of candidate genes at the resistance locus on chromosome 1 and validation of the mutation causing resistance. A substantial amount of preliminary data has been obtained in support of this proposal. In addition to the susceptible ROCK and well characterized SP strains, we have isolated two congenic resistant strains. The CKR strain contains the resistance factors from the SP strain introgressed into the background of the ROCK strain, and the KR strain contains only the kdr mutation in the background of ROCK. We have also conducted a transcriptomic (RNAseq) and proteomic analysis of these strains which will facilitate our selection of candidate genes at the resistance locus. These experiments will allow us to identify a new pyrethroid resistance mutation in A. aegypti and will give us preliminary information about its frequency in other populations of A. aegypti from across the globe. These data will provide new information about the similarities and differences that insecticide selection has had on geographically distant populations. Our results will form the basis for future studies of resistance monitoring and resistance management in this important vector of human disease.