Integration of whole genome sequencing and transcriptomics reveals a complex picture of the reestablishment of insecticide resistance in the major malaria vector Anopheles coluzzii.
Integration of whole genome sequencing and transcriptomics reveals a complex picture of the reestablishment of insecticide resistance in the major malaria vector Anopheles coluzzii.
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DOI：
10.1371/journal.pgen.1009970
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发表时间：
2021-12
期刊：
影响因子：
4.5
通讯作者：
Ranson H
中科院分区：
文献类型：
--
作者：
Ingham VA;Tennessen JA;Lucas ER;Elg S;Yates HC;Carson J;Guelbeogo WM;Sagnon N;Hughes GL;Heinz E;Neafsey DE;Ranson H
抗药性是疟疾控制成果的主要威胁，自2015年以来，疟疾控制成果一直停滞不前，并可能出现逆转。对杀虫剂抗药性的因果机制的研究正在描绘一幅日益复杂的画面，强调需要设计和实施针对这一表型的研究。在这项研究中，我们比较了三个群体的主要疟疾媒介安。coluzzii：具有相同遗传背景的一个敏感群体和两个抗性群体。最初定殖的耐药种群在6个月内迅速丧失耐药性，该种群的一个亚群用拟除虫菊酯重新选择，该种群的第三个种群也未丧失耐药性。对原始抗性、易感性和重新选择的菌落进行RNAseq和全基因组测序，其鉴定了与抗性相关的转录组和基因组的许多变化。首先，与易感对照相比，在两个抗性群体中均观察到氧化磷酸化途径内基因表达的增加;这通过呼吸速率增加进行表型转化，表明代谢升高与抗性直接相关。基因组测序突出了几个明显与抗性相关的区块，包括2 Rb倒位。最后，观察到微生物组谱的变化，表明微生物组成可能在抗性表型中起作用。总之，这项研究揭示了一个高度复杂的表型，其中多个转录组，基因组和微生物组的变化联合收割机，导致杀虫剂抗性。主要疟疾病媒的抗药性是对疟疾控制方案的最大威胁，因为这些方案严重依赖基于杀虫剂的干预措施。使用多组学方法研究耐药性已被证明是困难的，因为使用了在实验室环境中已定殖数十年的易感对照人群，由于不同的遗传背景，导致数据中存在大量噪音。在这里，我们利用来自布基纳法索的耐药按蚊coluzzii人口，在6个月内迅速失去抗性的衍生人口，以及在失去抗性后重新选择的人口，以探索杀虫剂抗性的致病机制。为了确定这种表型的根本原因，我们使用RNAseq，全基因组测序和基于实验室的验证来显示呼吸频率的变化，广泛的基因组变化和微生物组的改变与该人群的耐药性有关。这些发现表明了抗性的复杂性以及在田间环境中利用抗性诊断标记的挑战。
Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids, and a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance. Insecticide resistance in major malaria vectors represents the single biggest threat to malaria control programs, which are heavily reliant upon insecticide-based interventions. Studying resistance using multi-omics approaches has proven difficult due to the use of susceptible comparator populations that have been colonised in a laboratory setting for decades, leading to substantial noise in the data due to differing genetic backgrounds. Here, we utilise a resistant Anopheles coluzzii population from Burkina Faso, a derived population that rapidly lost resistance over a 6-month period, and a population re-selected after loss of resistance to explore causative mechanisms of insecticide resistance. To determine the underlying cause of this phenotype, we use RNAseq, whole genome sequencing and lab-based validation to show changes in respiratory rate, wide-ranging genomic changes and alterations in the microbiome are linked to resistance in this population. These findings demonstrate the complexity of resistance and the challenges in utilising diagnostic markers for resistance in a field setting.
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转录组分析揭示了由于亚肺上拟甲虫素暴露和杀虫剂耐药性按钮coluzzii而导致基因表达的明显变化。
影响因子：
4.4
作者：
Ingham VA;Brown F;Ranson H
通讯作者：
Ranson H
影响因子：
4.6
作者：
Jensen K;Ko AE;Schal C;Silverman J
通讯作者：
Silverman J
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
3
作者：
Bayili, Koama;N'do, Severin;Diabate, Abdoulaye
通讯作者：
Diabate, Abdoulaye
影响因子：
4.5
作者：
Grigoraki L;Cowlishaw R;Nolan T;Donnelly M;Lycett G;Ranson H
通讯作者：
Ranson H