结核菌对胆固醇的反应通过脂质利用调节器与环境pH和水平相结合
Yue Chen1, Nathan J MacGilvary1, Shumin Tan1
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
bioRxiv : the preprint server for biology
|September 4, 2023
概括
结核菌结核菌结合了环境线索和营养来源,用于宿主殖民. Mce3R调节器是协调对酸性pH,低和胆固醇反应的关键,影响毒性.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 宿主-病原体相互作用
背景情况:
- 了解Mycobacterium tuberculosis (Mtb) 如何整合环境信号和营养物质的可用性,以使宿主殖民仍然是一个挑战.
- 在感染期间,mtb利用宿主脂质,如胆固醇,作为主要的碳来源,特别是在酸性环境中,如颗粒瘤.
研究的目的:
- 调查菌群结核菌对环境线索和营养来源的细菌反应的整合.
- 确定参与协调Mtb对酸性pH,和胆固醇反应的调节者.
- 确定Mce3R在宿主体内的Mtb殖民和适应中的作用.
主要方法:
- 利用基于记者的屏幕来识别影响环境反应的Mtb脂质利用调节器.
- 进行了转录分析,以研究Mtb对酸性pH和胆固醇的反应.
- 为功能分析生成和表征一个删除突变 (∆mce3R).
- 在结核病的小鼠模型中评估了细菌殖民.
主要成果:
- 过度表达Mtb脂质调节剂改变了对低环境 (K+) 在酸性pH的反应.
- Mtb对酸性pH的反应被胆固醇放大,胆固醇的反应被酸性pH放大.
- 在组合条件下,删除*mce3R*消除了胆固醇增加和低[K+]反应.
- ∆*mce3R*突变在小鼠模型中显示了减弱的殖民化,特别是在富含脂质的病变中.
结论:
- Mce3R是一个关键的调节器,它集成了细菌对环境线索 (酸性pH,低K+) 和营养来源 (胆固醇) 的反应.
- 这种协调对于Mycobacterium tuberculosis的毒性和在脂质丰富的宿主环境中的殖民是必不可少的.
- 这些发现突出了细菌在感染期间适应和生存的新机制.
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