Transcriptomic and proteomic analysis of pyrethroid resistance in the CKR strain of Aedes aegypti.
Transcriptomic and proteomic analysis of pyrethroid resistance in the CKR strain of Aedes aegypti.
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DOI：
10.1371/journal.pntd.0009871
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发表时间：
2021-11
影响因子：
3.8
通讯作者：
Scott JG
中科院分区：
文献类型：
--
作者：
Sun H;Mertz RW;Smith LB;Scott JG
埃及伊蚊是人类病毒性疾病的重要传播媒介。这种蚊子分布在全球，在城市环境中繁殖，对人类健康构成严重威胁。拟除虫菊酯类杀虫剂一直是防治该虫的主要药剂。几十年来，埃及人一直在使用这种药物，但抗药性已经出现，使一些地区的控制成为问题。拟除虫菊酯抗性的一个主要机制是通过细胞色素P450单加氧酶（CYP）解毒，通常与一种或多种CYP的过表达有关。不幸的是，这种机制的分子基础仍然未知。我们使用RNA-seq和蛋白质组学分析相结合的方法来评估拟除虫菊酯抗性的分子基础，在高抗性的CKR菌株的A。埃及人。CKR菌株具有来自充分研究的新加坡（SP）菌株的抗性机制，该抗性机制渗入到易感的洛克菲勒（ROCK）菌株基因组中。RNA-seq和蛋白质组学数据是互补的;每一个都提供了另一种技术所不能提供的见解。然而，转录组学结果并没有定量反映蛋白质组学的结果。有10个CYP的转录本和蛋白质的表达均增加。这些CYP似乎在很大程度上是反式调节的，除了我们不能排除基因重复的一些CYP。我们确定了65个基因和lncRNA作为可能负责升高CKR中CYP的表达。抗性与1号染色体上的多个位点和3号染色体上的至少一个位点相关。我们还确定了5个CYP仅作为蛋白质过表达，这表明稳定的CYP蛋白可能是一种耐药机制。未来的研究，以提高分辨率的抗性位点，并检查候选基因和lncRNA确定这里将大大提高我们的理解CYP介导的抗性在A。埃及人。埃及伊蚊是人类病毒性疾病的重要媒介，通常使用拟除虫菊酯杀虫剂进行控制。这导致了这种蚊子通过两种主要机制进化出杀虫剂抗性：细胞色素P450蛋白（CYP）介导的拟除虫菊酯解毒增加和电压敏感钠通道（Vssc，拟除虫菊酯靶位点基因）突变。虽然对Vssc突变了解很多，但导致CYP介导的耐药的突变一直难以捉摸。我们使用了一个组合的转录组学和蛋白质组学的方法，试图确定CYP介导的高耐药CKR菌株的耐药性的分子基础。我们鉴定了CKR菌株中过表达的CYP，其中大多数表达增加是由于反式作用因子。我们确定了65个转录因子或长链非编码RNA（lncRNA），它们可能在这些CYP的表达增加中发挥作用。我们还发现了证据表明，稳定的蛋白质可能是一种耐药机制。
Aedes aegypti is an important vector of human viral diseases. This mosquito is distributed globally and thrives in urban environments, making it a serious risk to human health. Pyrethroid insecticides have been the mainstay for control of adult A. aegypti for decades, but resistance has evolved, making control problematic in some areas. One major mechanism of pyrethroid resistance is detoxification by cytochrome P450 monooxygenases (CYPs), commonly associated with the overexpression of one or more CYPs. Unfortunately, the molecular basis underlying this mechanism remains unknown. We used a combination of RNA-seq and proteomic analysis to evaluate the molecular basis of pyrethroid resistance in the highly resistant CKR strain of A. aegypti. The CKR strain has the resistance mechanisms from the well-studied Singapore (SP) strain introgressed into the susceptible Rockefeller (ROCK) strain genome. The RNA-seq and proteomics data were complimentary; each offering insights that the other technique did not provide. However, transcriptomic results did not quantitatively mirror results of the proteomics. There were 10 CYPs which had increased expression of both transcripts and proteins. These CYPs appeared to be largely trans-regulated, except for some CYPs for which we could not rule out gene duplication. We identified 65 genes and lncRNAs as potentially being responsible for elevating the expression of CYPs in CKR. Resistance was associated with multiple loci on chromosome 1 and at least one locus on chromosome 3. We also identified five CYPs that were overexpressed only as proteins, suggesting that stabilization of CYP proteins could be a mechanism of resistance. Future studies to increase the resolution of the resistance loci, and to examine the candidate genes and lncRNAs identified here will greatly enhance our understanding of CYP-mediated resistance in A. aegypti. Aedes aegypti is an important vector of human viral diseases and is commonly controlled using pyrethroid insecticides. This has led to the evolution of insecticide resistance in this mosquito via two main mechanisms: increased detoxification of pyrethroids mediated by cytochrome P450 proteins (CYPs) and mutations in the voltage sensitive sodium channel (Vssc, gene for the target site of pyrethroids). While much is known about the Vssc mutations, the mutation(s) causing the CYP-mediated resistance has been elusive. We used a combined transcriptomic and proteomic approach to try to identify the molecular basis of CYP-mediated resistance in the highly resistant CKR strain. We identified CYPs that were overexpressed in the CKR strain, and for most of these the increased expression was due to a trans-acting factor. We identified 65 transcription factors or long non-coding RNAs (lncRNAs) that may play a role in the increased expression of these CYPs. We also found evidence that stabilization of CYP proteins could be a mechanism of resistance.
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