Nutrient sensing modulates malaria parasite virulence.
Nutrient sensing modulates malaria parasite virulence.
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DOI：
10.1038/nature23009
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发表时间：
2017-07-13
期刊：
影响因子：
64.8
通讯作者：
Mota MM
中科院分区：
文献类型：
--
作者：
Mancio-Silva L;Slavic K;Grilo Ruivo MT;Grosso AR;Modrzynska KK;Vera IM;Sales-Dias J;Gomes AR;MacPherson CR;Crozet P;Adamo M;Baena-Gonzalez E;Tewari R;Llinás M;Billker O;Mota MM
细胞内病原体（如疟原虫）的生活方式与其宿主的生活方式密切相关，主要是为了营养供应。营养素不仅是能量的主要来源，而且还通过各种信号网络作为基因表达、代谢和生长的调节剂，这些信号网络赋予细胞感知和适应不同环境条件的能力。典型的营养感应途径可能是缺乏疟疾疟原虫的致病因子，从而提出了这些寄生虫是否具有感知和科普宿主营养波动的能力的问题。在这里，我们表明，疟原虫血液阶段的寄生虫积极响应宿主饮食热量的变化，通过重排其转录组伴随着显着的调整，他们的繁殖率。结合化学和遗传学方法的激酶组分析确定KIN作为介导营养物质感测并控制对宿主营养状态的转录反应的关键调节剂。KIN与SNF 1/AMPKα具有同源性，酵母互补研究表明古老的细胞能量传感途径的功能保守性。总的来说，这些发现揭示了一个关键的寄生虫营养感应机制，这是至关重要的调节寄生虫复制和毒力。
The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host(s), 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 signaling networks that confer to cells the ability to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumably absent in the causing agent of malaria Plasmodium, thus raising the question of whether these parasites possess the capacity to sense and cope with host nutrient fluctuations. Here, we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through a rearrangement of their transcriptome accompanied by a significant 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 to SNF1/AMPKα and yeast complementation studies suggest functional conservation of an ancient cellular energy sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical to modulate parasite replication and virulence.
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影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
影响因子：
5.6
作者：
Crozet P;Margalha L;Confraria A;Rodrigues A;Martinho C;Adamo M;Elias CA;Baena-González E
通讯作者：
Baena-González E
影响因子：
11.3
作者：
Conrad M;Schothorst J;Kankipati HN;Van Zeebroeck G;Rubio-Texeira M;Thevelein JM
通讯作者：
Thevelein JM
DOI：
10.1126/science.1215327
发表时间：
2012-05-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
通讯作者：
Hardie DG
影响因子：
--
作者：
Liu, Yang;Xu, Xinjing;Carlson, Marian
通讯作者：
Carlson, Marian