PDF(Pubmed)
Abstract：
Constant and extensive use of chemical insecticides has created a selection pressure and favored resistance development in many insect species worldwide. One of the most important pyrethroid resistance mechanisms is classified as target site insensitivity, due to conformational changes in the target site that impair a proper binding of the insecticide molecule. The voltage-gated sodium channel (NaV) is the target of pyrethroids and DDT insecticides, used to control insects of medical, agricultural and veterinary importance, such as anophelines. It has been reported that the presence of a few non-silent point mutations in the NaV gene are associated with pyrethroid resistance, termed as \'kdr\' (knockdown resistance) for preventing the knockdown effect of these insecticides. The presence of these mutations, as well as their effects, has been thoroughly studied in Anopheles mosquitoes. So far, kdr mutations have already been detected in at least 13 species (Anopheles gambiae, Anopheles arabiensis, Anopheles sinensis, Anopheles stephensi, Anopheles subpictus, Anopheles sacharovi, Anopheles culicifacies, Anopheles sundaicus, Anopheles aconitus, Anopheles vagus, Anopheles paraliae, Anopheles peditaeniatus and Anopheles albimanus) from populations of African, Asian and, more recently, American continents. Seven mutational variants (L1014F, L1014S, L1014C, L1014W, N1013S, N1575Y and V1010L) were described, with the highest prevalence of L1014F, which occurs at the 1014 site in NaV IIS6 domain. The increase of frequency and distribution of kdr mutations clearly shows the importance of this mechanism in the process of pyrethroid resistance. In this sense, several species-specific and highly sensitive methods have been designed in order to genotype individual mosquitoes for kdr in large scale, which may serve as important tolls for monitoring the dynamics of pyrethroid resistance in natural populations. We also briefly discuss investigations concerning the course of Plasmodium infection in kdr individuals. Considering the limitation of insecticides available for employment in public health campaigns and the absence of a vaccine able to brake the life cycle of the malaria parasites, the use of pyrethroids is likely to remain as the main strategy against mosquitoes by either indoor residual spraying (IR) and insecticide treated nets (ITN). Therefore, monitoring insecticide resistance programs is a crucial need in malaria endemic countries.
摘要：
化学杀虫剂的持续和广泛使用在全世界许多昆虫物种中产生了选择压力并有利于抗性发展。最重要的拟除虫菊酯抗性机制之一被归类为靶位点不敏感，由于靶位点的构象变化会损害杀虫剂分子的适当结合。电压门控钠通道（NaV）是拟除虫菊酯和DDT杀虫剂的靶标，用于控制医学昆虫，农业和兽医的重要性，如按蚊。据报道，NaV基因中一些非沉默点突变的存在与拟除虫菊酯抗性有关，被称为“kdr”(击倒抗性)，用于防止这些杀虫剂的击倒效果。这些突变的存在，以及它们的影响，已经对按蚊进行了彻底的研究。到目前为止,已经在至少13个物种中检测到kdr突变(冈比亚按蚊，阿拉伯按蚊，中华按蚊,Stephensi按蚊,亚平按蚊,萨卡罗氏按蚊,按蚊,按蚊,按蚊,迷走神经按蚊,副按蚊,非洲人口的peditaeniatus和albimanus按蚊），亚洲和,最近,美洲大陆。七个突变变体（L1014F，L1014S,L1014C,L1014W,N1013S,描述了N1575Y和V1010L)，L1014F的患病率最高，发生在NaVIIS6域的1014位点。kdr突变的频率和分布的增加清楚地表明了该机制在拟除虫菊酯抗性过程中的重要性。在这个意义上,已经设计了几种物种特异性和高度敏感的方法，以便大规模地对单个蚊子进行kdr基因分型，这可能是监测自然种群中拟除虫菊酯抗性动态的重要费用。我们还简要讨论了有关kdr个体中疟原虫感染过程的调查。考虑到可用于公共卫生运动的杀虫剂有限，并且缺乏能够阻止疟疾寄生虫生命周期的疫苗，通过室内残留喷洒（IR）和经杀虫剂处理的蚊帐（ITN），拟除虫菊酯的使用可能仍然是主要的防治蚊子的策略。因此,监测杀虫剂抗性计划是疟疾流行国家的关键需求。
