Modulation of Anopheles stephensi gene expression by nitroquine, an antimalarial drug against Plasmodium yoelii infection in the mosquito.

Modulation of Anopheles stephensi gene expression by nitroquine, an antimalarial drug against Plasmodium yoelii infection in the mosquito.
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硝基喹(一种抗约氏疟原虫感染的抗疟药)对斯氏按蚊基因表达的调节

DOI:
10.1371/journal.pone.0089473
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Huang F
Huang F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang J;Zhang S;Wang Y;Xu W;Zhang J;Jiang H;Huang F

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抗疟疾药物可能会影响蚊子对疟原虫的防御。我们以前的研究表明,硝喹显着减少约氏疟原虫感染斯氏按蚊,但其潜在的机制尚不清楚。为了了解如何传输能力的一个。为了研究硝喹对stephensi的影响,我们探索了不同处理后成年雌性的转录组,检测了基因表达谱的变化,并鉴定了受药物和寄生虫影响的转录物。我们将大规模并行测序和数据分析(包括基因发现,表达谱分析和功能预测)扩展到An。斯氏疟原虫感染前和感染后用或不用硝喹治疗。使用组装成特定重叠群的读段的数量来计算相对丰度(RA),我们根据RA值的差异将组装的重叠群分为四组:感染诱导的、感染抑制的、药物诱导的和药物抑制的。我们发现,在血粉和疟原虫感染中的硝喹改变了蚊子基因的转录,这些基因涉及不同的过程,包括病原体识别、信号转导、酚氧化酶原激活、细胞骨架组装、细胞粘附和氧化应激。这种差异基因表达可能促进了安氏按蚊的某些防御反应。stephensi对抗寄生虫并降低其感染性。我们的研究表明,硝喹可能在基因转录水平上调节蚊子抗疟原虫感染的几种免疫机制。这突出表明需要更好地了解抗疟药物对寄生虫存活和传播的影响。此外,我们的数据在很大程度上丰富了An的现有序列信息。stephensi,一种流行病学上重要的病媒物种。
Antimalarial drugs may impact mosquito’s defense against Plasmodium parasites. Our previous study showed nitroquine significantly reduced infection of Anopheles stephensi by Plasmodium yoelii, but the underlying mechanism remains unclear. In order to understand how transmission capacity of An. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the drug and parasite. We extended massively parallel sequencing and data analysis (including gene discovery, expression profiling, and function prediction) to An. stephensi before and after Plasmodium infection with or without nitroquine treatment. Using numbers of reads assembled into specific contigs to calculate relative abundances (RAs), we categorized the assembled contigs into four groups according to the differences in RA values infection induced, infection suppressed, drug induced, and drug suppressed. We found both nitroquine in the blood meal and Plasmodium infection altered transcription of mosquito genes implicated in diverse processes, including pathogen recognition, signal transduction, prophenoloxidase activation, cytoskeleton assembling, cell adhesion, and oxidative stress. The differential gene expression may have promoted certain defense responses of An. stephensi against the parasite and decreased its infectivity. Our study indicated that nitroquine may regulate several immune mechanisms at the level of gene transcription in the mosquito against Plasmodium infection. This highlights the need for better understanding of antimalarial drug’s impact on parasite survival and transmission. In addition, our data largely enriched the existing sequence information of An. stephensi, an epidemiologically important vector species.
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