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

埃及伊蚊1号染色体拟除虫菊酯抗性突变的鉴定

• 批准号: 10057017
• 负责人: Jeffrey G Scott
• 金额: $ 22.98万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057017
• 关键词: Address; Adult; Aedes; Biochemical; Candidate Disease Gene; Centromere; Chromosome 1; Clustered Regularly Interspaced Short Palindromic Repeats; Culicidae; DNA sequencing; Data; Dengue; Detection; Evaluation; Evolution; Frequencies; Future; Genes; Genetic; Genetic Polymorphism; Genome; Genomics; Goals; Grant; Insecticides; Knock-in; Knock-out; Maps; Mediating; Monitor; Mutation; Population; Population Genetics; Predisposition; Process; Proteomics; Resistance; Resistance development; Resolution; Role; Technology; Validation; ZIKA; candidate selection; congenic; design; disorder control; experimental study; genetic evolution; genetic resistance; geographically distant; human disease; nanopore; programs; pyrethroid; resistance allele; resistance factors; resistance gene; resistance mutation; resistant strain; transcriptome sequencing; transcriptomics; vector; vector control; vector mosquito

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.

总结/摘要： 在这里，我们试图了解伊蚊对拟除虫菊酯类杀虫剂的抗性的演变 埃及伊蚊是登革热和寨卡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产生了抗药性， 这代表了控制这种媒介及其传播的疾病的全球挑战。找到 延缓蚊子病媒对少数几种可利用的 杀虫剂是关键。要做到这一点，必须确定导致耐药性的突变 为了设计灵敏和精确的监测方案， 遗传学和抗性的进化，并设计有效的对策，以减缓 发展抵抗力。 我们的长期目标是开发监测耐药等位基因的必要技术， 可以研究这一重要的进化过程，从而可以 耽搁了我们的短期目标是确定新发现的 拟除虫菊酯抗性基因位于A.埃及人。为了实现短期目标，我们将 追求两个具体目标： 目标1。以高分辨率确定1号染色体上的抗性位点。 目标2.在1号染色体上的抗性基因座处的候选基因的评估和 验证导致耐药性的突变。 已经获得了大量的初步数据来支持这一建议。除了 敏感的ROCK和特征良好的SP菌株，我们已经分离出两个同源抗性 菌株CKR菌株含有来自SP菌株的抗性因子，所述抗性因子渗入到 ROCK株的背景，而KR株在背景中仅含有kdr突变 的岩石。我们还对这些基因进行了转录组学（RNAseq）和蛋白质组学分析。 这将有助于我们在抗性位点上选择候选基因。 这些实验将使我们能够确定一个新的拟除虫菊酯抗性突变的A。埃及和 将为我们提供关于其在其他A种群中频率的初步信息。埃及人从对面 地球仪。这些数据将提供有关相似性和差异的新信息， 杀虫剂的选择对地理上遥远的种群产生了影响。我们的研究结果将成为 为今后在这一重要媒介中进行抗药性监测和抗药性管理的研究， 人类疾病。