Grupo de Investigaciones Microbiológicas-UR (GIMUR), Programa de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá, Colombia.
Programa de Estudio y Control de Enfermedades Tropicales (PECET), Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Parasit Vectors. 2019 Jul 12;12(1):348. doi: 10.1186/s13071-019-3603-8.
In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis.
Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes.
A total of 723 differentially expressed genes were identified between resistant and sensitive lines. Comparative transcriptomic analysis revealed that genes encoding proteins involved in metabolism (fatty acids) and stress response, as well as those associated with antimony resistance in other Leishmania species, were upregulated in the antimony-resistant line. Most importantly, we observed upregulation of genes encoding autophagy proteins, suggesting that in the presence of trivalent stibogluconate (Sb) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites.
This work identified global transcriptomic changes in an in vitro-adapted strain in response to Sb. Our results provide relevant information to continue understanding the mechanism used by parasites of the subgenus Leishmania (L. amazonensis) to generate an antimony-resistant phenotype.
在过去的十年中，由于耐药菌株的出现，抗锑药物的耐药性已成为一个严重的问题。因此，了解利什曼原虫寄生虫在药物压力下生存所使用的机制至关重要，特别是对于具有医学-兽医重要性的物种，如 L. amazonensis。
在这里，我们使用 RNA-seq 技术分析转录组谱，并确定抗锑和敏感 L. amazonensis 前鞭毛体之间基因表达的全局变化。
在耐药和敏感系之间共鉴定出 723 个差异表达基因。比较转录组分析表明，编码参与代谢（脂肪酸）和应激反应的蛋白质的基因，以及与其他利什曼原虫物种中的锑耐药相关的基因，在锑耐药系中上调。最重要的是，我们观察到编码自噬蛋白的基因上调，这表明在三价葡甲胺（Sb）存在下，L. amazonensis 可以激活这些基因，无论是作为生存策略还是诱导细胞死亡，就像在其他寄生虫中观察到的那样。
这项工作鉴定了体外适应株对 Sb 反应的全转录组变化。我们的结果为继续了解亚属利什曼原虫（L. amazonensis）寄生虫产生锑耐药表型所使用的机制提供了相关信息。
