Determining the levels of resistance and patterns of cross-resistance for common kdr alleles in Aedes aegypti

总结/摘要： 在这里，我们试图了解埃及伊蚊对拟除虫菊酯类杀虫剂的抗性演变， 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 用于控制成年伊蚊，但在许多种群中已经产生了抗药性，代表了全球 控制这种媒介及其传播的疾病的挑战。寻找战略， 蚊媒对少数可用杀虫剂产生抗药性至关重要。做 因此，必须确定由常见抗性等位基因赋予的抗性水平， 针对电压敏感钠通道（VSSC）的杀虫剂。这些信息将填补一个 我们对耐药性演变的理解存在关键的数据缺口， 存在于发现不同抗性等位基因的种群中。 我们的长期目标是了解不同的Vssc等位基因在进化中的重要性， 这样就可以理解这一重要过程， 被耽搁了。 我们的短期目标是测量不同Vssc突变所赋予的耐药性水平 存在于地球仪的人群中。为了实现这一目标，我们将追求两个具体目标。 目标1。分离出7个同源（与敏感的利物浦菌株）菌株，它们具有 常见的未研究的Vssc抗性等位基因。 目标2.确定每个Vssc等位基因对20种杀虫剂的抗性水平 攻击VSSC 这一提议填补了我们对A. aegypti 通过量化不同等位基因赋予的表型。此外，我们的结果将 证明每个等位基因赋予的交叉抗性谱。这些信息将 为我们提供了一个大大提高的了解拟除虫菊酯抗性在A。埃及，产量 这一人类疾病重要载体耐药性管理的关键信息。

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 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 level of resistance conferred, by common resistance alleles, to insecticides that target the voltage sensitive sodium channel (VSSC). This information will fill a critical data gap in our understanding of the evolution of resistance and will inform what options exist in populations where the different resistance alleles are found. Our long-term goals are to understand the importance of different Vssc alleles in the evolution of resistance so that this important process can be understood and the development of resistance can be delayed. Our short-term goal is to measure the level of resistance conferred by different Vssc mutations found in populations across the globe. To accomplish this goal we will pursue two specific aims. Aim 1. Isolate seven congenic (to the susceptible Liverpool strain) strains that have one of the common unstudied Vssc resistance alleles. Aim 2. Determine the level of resistance conferred by each Vssc allele to twenty insecticides that target the VSSC. This proposal fills an important data gap in our understanding of insecticide resistance in A. aegypti by quantitating the phenotype that the different alleles confer. In addition, our results will demonstrate what cross-resistance spectrum is conferred by each allele. This information will provide us with a vastly improved understanding of pyrethroid resistance in A. aegypti, and yield key information for resistance management in this important vector of human disease.