在抗素治疗的Plasmodium falciparum中表观遗传赋予的环状生存率
Xinyu Yu1,2,3, Jincan He4,5, Changhong Wang1,6,7
1Laboratory of Molecular Parasitology, State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Nature communications
|August 28, 2025
概括
疟疾寄生虫对素的抵抗与表观遗传变化有关. 该研究确定PfMYST是寄生虫生存的关键调节剂,为抗疟疾药物开发提供了新的点.
科学领域:
- 疟疾学
- 表观遗传学
- 寄生虫学
背景情况:
- 基于素的组合疗法 (ART) 对于治疗疟疾至关重要.
- 对ART的部分耐药性与Plasmodium falciparum寄生虫的环状生存率 (RS) 的增加有关.
- 人们越来越认识到表观遗传机制是药物耐药性的贡献者.
研究的目的:
- 系统地评估Plasmodium falciparum histone acetyltransferases (HATs) 在素耐药性的作用.
- 在ART治疗后确定涉及寄生虫存活的特定表观遗传调节剂.
- 阐明表观遗传因素与已知的抗性机制,如PfK13突变之间的相互作用.
主要方法:
- 在多个实地分离物中选所有可谓的Plasmodium falciparum HAT.
- 基因淘汰实验以评估PfMYST表达对RS的功能影响.
- 单细胞RNA测序,ChIP-seq和CRISPR/cas9用于基因识别和验证.
- 进行多组学分析,研究PfMYST和PfK13之间的相互作用.
主要成果:
- 确定pfMYST是唯一完全与RS表型调制相关的HAT.
- 击败PfMYST证实了它与RS的联系,伴随着代谢过程的改变.
- 在RS中涉及的pfMYST向基因被确定并得到功能验证.
- 观察到PfMYST和PfK13机制在赋予甲素部分耐药性的显著相互作用.
- 发现pfMYST介导的表观遗传调节也会影响对其他抗疟疾药物的耐药性.
结论:
- PfMYST是Plasmodium falciparum环状阶段存活的关键表观遗传调节剂,也是对素的部分耐药性的调节剂.
- 针对PfMYST提供了一种潜在的策略来克服或预防对ART和其他抗疟疾药物的耐药性.
- 这项研究提供了对疟疾寄生虫抗药性表观遗传学的关键见解.
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