Hirata Koichi, Komagata Osamu, Itokawa Kentaro, Yamamoto Atsushi, Tomita Takashi, Kasai Shinji
Department of Environmental and Toxicology, Odawara Research Center, Nippon-soda Co., Ltd., Odawara, Kanagawa, Japan.
Department of Medical Entomology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
PLoS Negl Trop Dis. 2014 Aug 28;8(8):e3085. doi: 10.1371/journal.pntd.0003085. eCollection 2014 Aug.
The voltage-sensitive sodium (Na+) channel (Vssc) is the target site of pyrethroid insecticides. Pest insects develop resistance to this class of insecticide by acquisition of one or multiple amino acid substitution(s) in this channel. In Southeast Asia, two major Vssc types confer pyrethroid resistance in the dengue mosquito vector Aedes aegypti, namely, S989P+V1016G and F1534C. We expressed several types of Vssc in Xenopus oocytes and examined the effect of amino acid substitutions in Vssc on pyrethroid susceptibilities. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to permethrin by 100- and 25-fold, respectively, while S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to permethrin by 1100-fold. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to deltamethrin by 10- and 1-fold (no reduction), respectively, but S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to deltamethrin by 90-fold. These results imply that pyrethroid insecticides are highly likely to lose their effectiveness against A. aegypti if such a Vssc haplotype emerges as the result of a single crossing-over event; thus, this may cause failure to control this key mosquito vector. Here, we strongly emphasize the importance of monitoring the occurrence of triple mutations in Vssc in the field population of A. aegypti.
电压敏感钠（Na+）通道（Vssc）是拟除虫菊酯类杀虫剂的作用靶点。害虫通过在该通道中获得一个或多个氨基酸取代而对这类杀虫剂产生抗性。在东南亚，两种主要的Vssc类型赋予登革热蚊媒埃及伊蚊对拟除虫菊酯的抗性，即S989P+V1016G和F1534C。我们在非洲爪蟾卵母细胞中表达了几种类型的Vssc，并研究了Vssc中的氨基酸取代对拟除虫菊酯敏感性的影响。S989P+V1016G和F1534C单倍型分别使通道对氯菊酯的敏感性降低了100倍和25倍，而S989P+V1016G+F1534C三重突变使通道对氯菊酯的敏感性降低了1100倍。S989P+V1016G和F1534C单倍型分别使通道对溴氰菊酯的敏感性降低了10倍和1倍（无降低），但S989P+V1016G+F1534C三重突变使通道对溴氰菊酯的敏感性降低了90倍。这些结果表明，如果这样的Vssc单倍型因单次交叉事件而出现，拟除虫菊酯类杀虫剂很可能会失去对埃及伊蚊的有效性；因此，这可能导致无法控制这一关键蚊媒。在此，我们强烈强调监测埃及伊蚊野外种群中Vssc三重突变发生情况的重要性。
