Translational reprogramming as a driver of antimony-drug resistance in Leishmania.
Translational reprogramming as a driver of antimony-drug resistance in Leishmania.
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DOI：
10.1038/s41467-023-38221-1
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发表时间：
2023-05-05
影响因子：
16.6
通讯作者：
Karamysheva, Zemfira N.
中科院分区：
文献类型：
--
作者：
Guarnizo, Sneider Alexander Gutierrez;Tikhonova, Elena B.;Karamyshev, Andrey L.;Muskus, Carlos E.;Karamysheva, Zemfira N.
利什曼原虫是一种单细胞原生动物，具有有限的转录控制，主要使用基因表达的转录后调节，尽管该过程的分子机制仍然知之甚少。利什曼病的治疗，与利什曼原虫感染相关的病理，由于耐药性而受到限制。在这里，我们报告了锑耐药和敏感菌株在全翻译组水平的mRNA翻译的显着差异。主要的差异（2431差异翻译的成绩单）证明了在没有药物压力的支持，复杂的先发制人的适应，需要有效地补偿生物适应性的损失，一旦他们暴露于锑。相反，暴露于锑的抗药性寄生虫只激活了156个转录本的高度选择性翻译。这种选择性mRNA翻译与表面蛋白重排、优化能量代谢、阿马斯汀上调和改善抗氧化反应有关。我们提出了一个新的模型，建立翻译控制作为一个主要的驱动力的锑耐药表型利什曼原虫。利什曼原虫是一种单细胞原生动物，具有有限的转录控制。在这里，作者表明，翻译控制是利什曼原虫锑耐药的主要机制。他们观察到在对药物的耐药性发展过程中戏剧性的翻译组重编程，并报告翻译控制是锑耐药表型的主要驱动因素。
Leishmania is a unicellular protozoan that has a limited transcriptional control and mostly uses post-transcriptional regulation of gene expression, although the molecular mechanisms of the process are still poorly understood. Treatments of leishmaniasis, pathologies associated with Leishmania infections, are limited due to drug resistance. Here, we report dramatic differences in mRNA translation in antimony drug-resistant and sensitive strains at the full translatome level. The major differences (2431 differentially translated transcripts) were demonstrated in the absence of the drug pressure supporting that complex preemptive adaptations are needed to efficiently compensate for the loss of biological fitness once they are exposed to the antimony. In contrast, drug-resistant parasites exposed to antimony activated a highly selective translation of only 156 transcripts. This selective mRNA translation is associated with surface protein rearrangement, optimized energy metabolism, amastins upregulation, and improved antioxidant response. We propose a novel model that establishes translational control as a major driver of antimony-resistant phenotypes in Leishmania. Leishmania is a unicellular protozoan that has limited transcriptional control. Here, the authors show that translational control is a major mechanism of antimony drug resistance in Leishmania. They observe a dramatic translatome reprogramming during development of resistance to the drug and report translational control as a major driver of antimony-resistant phenotypes.
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DOI：
10.1016/j.bbamcr.2018.08.006
发表时间：
2019-01
期刊：
Biochimica et biophysica acta. Molecular cell research
影响因子：
--
作者：
Kolupaeva V
通讯作者：
Kolupaeva V
影响因子：
--
作者：
Bhargava, Prachi;Singh, Rajni
通讯作者：
Singh, Rajni
影响因子：
4.6
作者：
Camacho, Esther;Gonzalez-de La Fuent, Sandra;Aguado, Begoiia
通讯作者：
Aguado, Begoiia
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
DOI：
10.1007/978-1-0716-0294-2_7
发表时间：
2020-01-01
期刊：
TRYPANOSOMATIDS
影响因子：
--
作者：
Bajak, Kathrin;Clayton, Christine
通讯作者：
Clayton, Christine