结核菌甲基转移酶Rv2067c操纵宿主表观遗传编程,以促进自己的生存
Prakruti R Singh1,2, Venkatareddy Dadireddy3, Shubha Udupa1
1Department of Microbiology & Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.
Nature communications
|December 21, 2023
概括
结核菌使用Rv2067c来改变宿主表观遗传,抑制炎症并促进生存. 这种甲基转移酶劫持了组织素甲基化,有助于巨细胞内的细菌繁殖.
科学领域:
- 微生物学 微生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 宿主-病原体相互作用
背景情况:
- 结核菌 (M. tuberculosis) 使用复杂的机制来逃避宿主免疫防御.
- 表观遗传修饰在调节宿主对感染反应方面发挥着至关重要的作用.
研究的目的:
- 阐明M.结核病甲基转移酶Rv2067c在调节宿主表观遗传机制中的作用.
- 了解Rv2067c如何对M.结核病的生存和巨细胞内的病原体产生有所贡献.
主要方法:
- 对Rv2067c和宿主DOT1L.L.的结构分析
- 在受感染的巨细胞中检测 histone H3K79 的甲基化模式.
- 评估宿主细胞死亡途径 (亡和亡) 和炎症基因表达.
主要成果:
- Rv2067c在非核细胞组的环境中甲基化希斯H3K79,与宿主DOT1L不同.
- Rv2067c降低了DOT1L活性,减少了H3K79me3在促炎基因上的作用.
- 这种表观遗传调节抑制了酶-8依赖的亡,并增强了RIPK3介导的亡,增加了病原性.
- Rv2067c对SESTRIN3,NLRC3和TMTC1进行上调,有助于逃避宿主炎症和氧化应激反应.
结论:
- 结核菌利用Rv2067c作为重编程宿主表观遗传的关键效应因子,以求生存.
- Rv2067c和DOT1L之间的结构和功能差异使得M.结核病能够有效地操纵宿主信号通路.
- 针对Rv2067c介导的表观遗传修饰是一种潜在的抗结核战略.
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