埃及伊蚊对拟除虫菊酯的抗药性:赋予击倒抗性、恢复和死亡的基因组变异。

Permethrin resistance in Aedes aegypti: Genomic variants that confer knockdown resistance, recovery, and death.

机构信息

Colorado State University, Department of Microbiology, Immunology and Pathology, Center of Vector-borne and Infectious Diseases, Fort Collins, Colorado, United States of America.

Centers for Diseases Prevention and Control, Arboviral Diseases Branch, Fort Collins, Colorado, United States of America.

出版信息

PLoS Genet. 2021 Jun 17;17(6):e1009606. doi: 10.1371/journal.pgen.1009606. eCollection 2021 Jun.

Abstract

Pyrethroids are one of the few classes of insecticides available to control Aedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur in Ae. aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site-the voltage-gated sodium channel (VGSC)-and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations at VGSC and moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.

摘要

拟除虫菊酯是控制埃及伊蚊(登革热、基孔肯雅热和寨卡病毒的主要传播媒介)的少数杀虫剂之一。不幸的是,蚊虫种群中拟除虫菊酯抗性的进化机制威胁到我们控制疾病爆发的能力。埃及伊蚊中存在两种常见的拟除虫菊酯抗性机制:1)击倒抗性,涉及到拟除虫菊酯靶标——电压门控钠离子通道(VGSC)上的氨基酸取代;2)解毒酶增强代谢。当异质种群的蚊子暴露于拟除虫菊酯时,会产生不同的反应。在暴露期间,一部分蚊子会立即被击倒,而其他蚊子则不会被击倒,并被指定为击倒抗性(kdr)。当这些个体从杀虫剂源中移除时,被击倒的蚊子要么保持这种状态并导致死亡,要么在几个小时内恢复。这些表型反应的比例取决于拟除虫菊酯的浓度和所测试种群的遗传背景。在这项研究中,我们对来自墨西哥塔帕丘拉的抗药性蚊群中的 kdr、恢复和死亡表型进行了测序和成对基因组比较。我们确定了与每种表型相关的单核苷酸多态性(SNP),并确定了可能与拟除虫菊酯抗性机制相关的基因,包括解毒、表皮和杀虫剂靶标。我们发现 kdr 与 VGSC 突变高度相关,与其他杀虫剂靶标、解毒和表皮蛋白编码基因中度相关。恢复与表皮蛋白、电压依赖性钙通道和一组不同的解毒基因相关。我们提供了一个在该领域抗性种群中受定向选择影响的解毒基因列表。它们在拟除虫菊酯代谢中的功能作用及其作为抗性基因组标记的潜在用途需要进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/742b/8211209/1734e91b47aa/pgen.1009606.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索