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Nutrient sensing modulates malaria parasite virulence

机译：营养感应调节疟原虫的毒力

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摘要

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions(1,2). Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium(3-5), thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPK alpha, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.
机译：细胞内病原体（例如疟原虫）的生活方式与其寄主的生活方式密切相关，主要是为了提供营养。营养素不仅通过各种信号传递网络作为细胞的主要能源，而且还作为基因表达，代谢和生长的调节剂，使细胞能够感知并适应各种环境条件（1,2）。疟疾的病原体（Plasmodium，3-5）被认为缺乏典型的养分感应途径，因此提出了这些寄生虫是否能够感应和应对宿主养分水平波动的问题。在这里，我们显示疟原虫血液阶段的寄生虫通过其转录组的重排以及其繁殖率的大幅调整，积极响应宿主的饮食热量变化。结合蛋白质组学和遗传学方法进行的激酶组分析确定KIN为关键调节因子，可调节营养素的感知并控制对宿主营养状况的转录反应。 KIN与SNF1 / AMPK alpha具有同源性，酵母互补研究表明它是功能上保守的细胞能量传感途径的一部分。总体而言，这些发现揭示了一个关键的寄生虫养分感应机制，该机制对于调节寄生虫的复制和毒力至关重要。

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  • 来源
    《Nature》 |2017年第7662期|213-216|共4页
  • 作者

    Mancio-Silva Liliana; Slavic Ksenija; Ruivo Margarida T. Grilo; Grosso Ana Rita; Modrzynska Katarzyna K.; Vera Iset Medina; Sales-Dias Joana; Gomes Ana Rita; MacPherson Cameron Ross; Crozet Pierre; Adamo Mattia; Baena-Gonzalez Elena; Tewari Rita; Llinas Manuel; Billker Oliver; Mota Maria M.;

  • 作者单位

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England;

    Inst Pasteur, F-75724 Paris, France;

    Inst Gulbenkian Ciencias, Oeiras, Portugal;

    Inst Gulbenkian Ciencias, Oeiras, Portugal;

    Inst Gulbenkian Ciencias, Oeiras, Portugal;

    Univ Nottingham, Sch Life Sci, Queens Med Ctr, Nottingham, England;

    Penn State Univ, Ctr Malaria Res, Dept Chem, Dept Biochem & Mol Biol, State Coll, PA 16802 USA|Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA 16802 USA;

    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England;

    Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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