부산대학교 도서관

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. Author summary: Dengue, Zika, and chikungunya are viral diseases transmitted by the mosquito Aedes aegypti. Unfortunately, no vaccines or effective treatments are available, and public health strategies rely on the suppression of mosquito populations to reduce the impact of disease outbreaks. Pyrethroids are a common class of insecticides used to suppress mosquito populations. Unfortunately, mosquitoes have developed resistance to pyrethroids in several regions of the world, threatening disease control efforts. Since few classes of insecticides are available for public health, we have to find strategies that prevent or prolong the use of pyrethroids. Therefore, we need to understand mechanisms of resistance and develop methods to quantify these mechanisms in field populations before they become a threat to vector control strategies. Quantifying the frequency of mutations associated with target site resistance provides information about the presence of this mechanism in mosquito populations; however, we still need to understand additional mechanisms of resistance (e.g., metabolism, cuticle penetration) that play an important role in the survival of mosquitoes. In this study, we sequenced the genome of resistant (kdr), recovered, and dead mosquitoes after insecticide exposure. Our aim is to identify genomic variants associated with specific mechanisms of resistance. The results will improve the identification of specific genomic markers associated with resistance in the Aedes aegypti from Southeastern Mexico. [ABSTRACT FROM AUTHOR]