结核菌PrrA与dosR促进体结合,并调节菌根菌对缺氧的适应
Yannik A Haller1, Jiapei Jiang2, Zijian Wan3
1School of Life Sciences, Arizona State University, Tempe, AZ, USA; Biodesign Institute Center for Bioelectronics and Biosensors, Arizona State University, Tempe, AZ, USA.
Tuberculosis (Edinburgh, Scotland)
|June 17, 2024
概括
两组 PrrAB 系统调节参与低氧生存的 Mycobacterium 结核病基因. 野生类型的PrrA蛋白显示出最高的DNA结合亲和力,在低氧状态下影响基因表达.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- PrrAB 两组件系统 (TCS) 对 Mycobacterium 结核病的生存至关重要.
- PrrA DNA 结合独立于 PrrB 介导的酸化发生.
- 非同源性激酶可以在氨酸-6 (T6) 中对PrrA进行酸化.
研究的目的:
- 调查野生类型,相仿性和酸化性PrrA变体的差异性DNA结合亲和力和调节作用.
- 阐明M.结核病中PrrAB系统的酸化介导的调节机制.
- 了解菌根细菌低氧和低氧反应基因 (dosR和 cydA) 的控制.
主要方法:
- 使用了复合野生类型,模仿性 (D58E,T6E) 和缩性 (D58A,T6A) PrrA 蛋白质.
- 测量了对prrAMtb,dosRMtb和cydAMtb促进体的DNA结合亲和力.
- 在M. smegmatis菌株中构建了报告者基因融合 (促销者-mCherry),以在各种条件下评估调控活性.
主要成果:
- 与假设相反,野生型PrrAMtb表现出最高的DNA结合亲和力,特别是对dosRMtb促进子 (KD 3.46 ± 2.09 nM).
- PrrAMtb证明了自我调节和诱导dosRMtb表达,特别是在体外低氧生长过程中.
- 对prrABMtb的联合表达显著诱导了cydiaMtb促进活性.
结论:
- 野生类型的PrrA蛋白在PrrAB系统中具有最强的DNA结合能力.
- PrrA自我调节和dosR诱导是依赖于缺氧的.
- 该PrrAB系统在调节dosR和cydA基因中发挥着重要作用,以应对菌根体中低氧环境.
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