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PfAP2-MRP DNA 结合蛋白是疟疾寄生虫血液阶段寄生虫病变的主要调节者

Amit Kumar Subudhi¹, Judith L Green², Rohit Satyam³

¹Pathogen Genomics Group, Bioscience Program, Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia.

bioRxiv : the preprint server for biology

|June 9, 2023

概括

杆菌的主调节器PfAP2-MRP控制寄生虫的发展,变基因表达和染色质结构在内红细胞周期. 它的删除会影响寄生虫的生长,免疫逃避和性阶段转换.

科学领域:

分子寄生虫学分子寄生虫学
转录条例转录条例转录条例
疟疾的发病因子疟疾的发病因子

背景情况:

疟疾寄生虫Plasmodium falciparum重塑红细胞 (RBC),表达变异性蛋白质以逃避免疫.
调节寄生虫发育和毒性的分子机制尚不清楚.

研究的目的:

为了鉴定Plasmodium falciparum中必不可少的Plasmodium Apicomplexan AP2 (ApiAP2) 转录因子PfAP2-MRP的特征.
阐明PfAP2-MRP在调节寄生虫发育,毒性和基因表达在红细胞内发育周期 (IDC) 的作用.

主要方法:

可以诱导的基因淘汰PfAP2-MRP.
染色体免疫沉测序 (ChIP-seq) 用于识别DNA结合部位.
单细胞RNA测序 (scRNA-seq) 和光激活细胞分类 (FACS) 用于基因表达分析.
染色体构造捕获 (Hi-C) 来评估染色体相互作用.

主要成果:

PfAP2-MRP对于虫阶段的寄生虫发育,变基因调节,虫发育和寄生虫退出至关重要.
ChIP-seq揭示了PfAP2-MRP与调节热细胞发育,宿主细胞重塑,抗原变异和致病性的促进体结合.
删除PfAP2-MRP导致了Var基因的去抑制,性细胞标记物的过度表达,并减少了异色染色素中的染色体内和染色体间相互作用.

结论:

PfAP2-MRP是一个重要的上游调节器,控制寄生虫的生长,染色质结构和在不同的IDC阶段的变基因表达.
PfAP2-MRP通过调节抗原变异和宿主细胞重塑来影响寄生虫的病原性.
PfAP2-MRP在过渡到性发育阶段的过程中发挥作用.

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