CYP 介导的埃及伊蚊对氯菊酯的抗性及其跨调控证据。
CYP-mediated permethrin resistance in Aedes aegypti and evidence for trans-regulation.
机构信息
Department of Entomology, Comstock Hall, Cornell University, Ithaca, New York, United States of America.
Department of Medical Entomology, National Institute of Infectious Diseases, Toyama, Shinjukuku, Tokyo, Japan.
出版信息
PLoS Negl Trop Dis. 2018 Nov 19;12(11):e0006933. doi: 10.1371/journal.pntd.0006933. eCollection 2018 Nov.
Aedes aegypti poses a serious risk to human health due to its wide global distribution, high vector competence for several arboviruses, frequent human biting, and ability to thrive in urban environments. Pyrethroid insecticides remain the primary means of controlling adult A. aegypti populations during disease outbreaks. As a result of decades of use, pyrethroid resistance is a global problem. Cytochrome P450 monooxygenase (CYP)-mediated detoxification is one of the primary mechanisms of pyrethroid resistance. However, the specific CYP(s) responsible for resistance have not been unequivocally determined. We introgressed the resistance alleles from the resistant A. aegypti strain, Singapore (SP), into the genetic background of the susceptible ROCK strain. The resulting strain (CKR) was congenic to ROCK. Our primary goal was to determine which CYPs in SP are linked to resistance. To do this, we first determined which CYPs overexpressed in SP are also overexpressed in CKR, with the assumption that only the CYPs linked to resistance will be overexpressed in CKR relative to ROCK. Next, we determined whether any of the overexpressed CYPs were genetically linked to resistance (cis-regulated) or not (trans-regulated). We found that CYP6BB2, CYP6Z8, CYP9M5 and CYP9M6 were overexpressed in SP as well as in CKR. Based on the genomic sequences and polymorphisms of five single copy CYPs (CYP4C50, 6BB2, 6F2, 6F3 and 6Z8) in each strain, none of these genes were linked to resistance, except for CYP6BB2, which was partially linked to the resistance locus. Hence, overexpression of these four CYPs is due to a trans-regulatory factor(s). Knowledge on the specific CYPs and their regulators involved in resistance is critical for resistance management strategies because it aids in the development of new control chemicals, provides information on potential environmental modulators of resistance, and allows for the detection of resistance markers before resistance becomes fixed in the population.
埃及伊蚊由于其广泛的全球分布、对几种虫媒病毒的高媒介效能、频繁叮咬人类以及在城市环境中茁壮成长的能力,对人类健康构成严重威胁。拟除虫菊酯类杀虫剂仍然是在疾病爆发期间控制成蚊埃及伊蚊种群的主要手段。由于几十年来的使用,拟除虫菊酯类杀虫剂抗性是一个全球性问题。细胞色素 P450 单加氧酶 (CYP) 介导的解毒是拟除虫菊酯类杀虫剂抗性的主要机制之一。然而,导致抗性的特定 CYP 尚未明确确定。我们将抗性等位基因从抗性埃及伊蚊品系新加坡 (SP) 导入易感 ROCK 品系的遗传背景中。由此产生的品系 (CKR) 与 ROCK 是同基因的。我们的主要目标是确定 SP 中的哪些 CYP 与抗性有关。为此,我们首先确定了在 SP 中过度表达的 CYP 也在 CKR 中过度表达,假设只有与抗性相关的 CYP 会在 CKR 中相对于 ROCK 过度表达。接下来,我们确定了任何过度表达的 CYP 是否与抗性有关(顺式调控)或无关(反式调控)。我们发现,CYP6BB2、CYP6Z8、CYP9M5 和 CYP9M6 在 SP 以及 CKR 中均过度表达。基于每个菌株中五个单拷贝 CYP(CYP4C50、6BB2、6F2、6F3 和 6Z8)的基因组序列和多态性,除了 CYP6BB2 部分与抗性基因座连锁外,这些基因均与抗性无关。因此,这些四个 CYP 的过度表达是由于一个反式调控因子(多个)引起的。对参与抗性的特定 CYP 及其调节剂的了解对于抗性管理策略至关重要,因为它有助于开发新的控制化学品,提供有关抗性潜在环境调节剂的信息,并在抗性在种群中固定之前检测到抗性标记。
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