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.

摘要/摘要： 在这里，我们试图了解伊蚊中对拟除虫菊酯杀虫剂的抗性的演变 埃及，登革热和寨卡等人类疾病的重要媒介。拟除虫菊酯杀虫剂 被广泛用于控制成年迪亚的人，但在许多人群中都有耐药性进化 代表控制该向量及其传播的疾病的全球挑战。发现 将蚊子向量推迟发展为少数可用的策略 杀虫剂至关重要。为此，必须确定负责抵抗的突变 为了设计敏感和精确的监控程序，了解人群 遗传学和抵抗的演变，并设计有效的对策以减慢 阻力的发展。 我们的长期目标是开发必要的技术来监视抗性等位基因，以便 可以研究这个重要的进化过程，因此抵抗的发展可以是 延迟。我们的短期目标是确定负责新确定的突变 A. aegypti中1染色体上的拟除虫菊酯抗性基因座。为了解决我们的短期目标，我们将 追求两个具体目标： AIM 1。确定高分辨率1染色体上的电阻基因座。 目标2。在染色体1和 验证突变导致抗性。 为了支持该提案，已经获得了大量的初步数据。此外 易感岩石和特征性良好的SP菌株，我们隔离了两种抗性 菌株。 CKR应变包含SP菌株渗入的电阻因子 岩石菌株的背景，KR应变仅包含背景中的KDR突变 岩石。我们还对这些进行了转录组（RNASEQ）和蛋白质组学分析 菌株将促进我们在电阻基因座选择候选基因的选择。 这些实验将使我们能够在A. eegypti和 将为我们提供有关其在其他A. A. A. A. A. A. A. A. A. aegypti的频率的初步信息 地球。这些数据将提供有关相似性和差异的新信息 选择杀虫剂对地理遥远的人群进行了选择。我们的结果将构成基础 为了将来研究抵抗监测和抵抗管理的研究 人类疾病。