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首页> 外文期刊>International Journal of Environmental Research and Public Health >Malpighian Tubules as Novel Targets for Mosquito Control
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Malpighian Tubules as Novel Targets for Mosquito Control

机译：Malpighian小管作为控制蚊子的新目标

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The Malpighian tubules and hindgut are the renal excretory tissues of mosquitoes; they are essential to maintaining hemolymph water and solute homeostasis. Moreover, they make important contributions to detoxifying metabolic wastes and xenobiotics in the hemolymph. We have focused on elucidating the molecular mechanisms of Malpighian tubule function in adult female mosquitoes and developing chemical tools as prototypes for next-generation mosquitocides that would act via a novel mechanism of action (i.e., renal failure). To date, we have targeted inward rectifier potassium (Kir) channels expressed in the Malpighian tubules of the yellow fever mosquito Aedes aegypti and malaria mosquito Anopheles gambiae . Inhibition of these channels with small molecules inhibits transepithelial K + and fluid secretion in Malpighian tubules, leading to a disruption of hemolymph K + and fluid homeostasis in adult female mosquitoes. In addition, we have used next-generation sequencing to characterize the transcriptome of Malpighian tubules in the Asian tiger mosquito Aedes albopictus , before and after blood meals, to reveal new molecular targets for potentially disrupting Malpighian tubule function. Within 24 h after a blood meal, the Malpighian tubules enhance the mRNA expression of genes encoding mechanisms involved with the detoxification of metabolic wastes produced during blood digestion (e.g., heme, NH 3 , reactive oxygen species). The development of chemical tools targeting these molecular mechanisms in Malpighian tubules may offer a promising avenue for the development of mosquitocides that are highly-selective against hematophagous females, which are the only life stage that transmits pathogens.
机译：Malpighian小管和后肠是蚊子的肾脏排泄组织。它们对于维持淋巴水和溶质体内稳态至关重要。此外，它们为排毒淋巴液中的代谢废物和异种生物排毒做出了重要贡献。我们专注于阐明成年雌性蚊子中Malpighian小管功能的分子机制，并开发出化学工具作为下一代灭蚊剂的原型，这些灭蚊剂将通过一种新的作用机制（即肾衰竭）起作用。迄今为止，我们已经针对了在黄热蚊，埃及伊蚊和疟疾冈比亚按蚊的马氏小管中表达的内向整流钾（Kir）通道。用小分子抑制这些通道可抑制Malpighian小管中的上皮K +和液体分泌，从而导致成年雌性蚊子的血淋巴K +和液体体内稳态受到破坏。此外，我们已经使用下一代测序技术来表征餐食前后亚洲虎蚊白纹伊蚊的马尔必小管的转录组，以揭示可能破坏马尔必小管功能的新分子靶标。餐后24小时内，马尔皮安氏小管增强了与血液消化过程中产生的代谢废物（例如血红素，NH 3，活性氧）解毒有关的编码机制的基因的mRNA表达。针对Malpighian小管中这些分子机制的化学工具的开发可能为开发对血吸虫雌性具有高度选择性的灭蚊剂提供了有希望的途径，后者是唯一传播病原体的生命阶段。

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