c-di-AMP-DasR信号轴介导了菌根细菌的抗酸性
Yu Fu1, Xue-Qin Xie1, Zhan-Hui Xu1
1Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
mBio
|February 6, 2026
概括
结核菌使用DasR调节器通过循环二-AMP (c-di-AMP) 感知酸度,提高其生存能力. 这种pH敏感通路涉及调节压力代谢物和稳定蛋白质,以获得强大的抗酸性.
科学领域:
- 微生物学和分子生物学
- 细菌病原体的产生
- 信号传输 信号传输
背景情况:
- 病原性菌根菌,包括 Mycobacterium 结核病,必须在感染期间在酸性宿主环境中生存.
- 抗酸机制对于菌根菌的生存和持久性至关重要.
- 第二信使信号在细菌适应环境压力的作用是一个活跃的研究领域.
研究的目的:
- 为了识别和描述参与Mycobacterium结核病酸适应的调节者.
- 阐明Mycobacterium结核病菌感知和响应酸性条件的分子机制.
- 研究循环二-AMP (c-di-AMP) 和其受体在菌根菌体应激反应中的作用.
主要方法:
- 在不同的pH条件下,生物化学测试以确定GntR家族调节器DasR与c-di-AMP的结合亲和力.
- 染色体免疫沉测序 (ChIP-seq) 用于识别DasR.的直接DNA标.
- 对基因表达变化的分析,包括核酸代谢基因和分子伴侣HtpG.
主要成果:
- 在Mycobacterium tuberculosis中,DasR被确定为一种保存的c-di-AMP受体,与中性pH (Kd = 226 μM) 相比,在酸性pH (Kd = 11.4 μM) 中对c-di-AMP的亲和力是20倍的.
- DasR直接调节参与核酸代谢的基因,通过积极的反来动态控制 (p) pGpp,cAMP和c-di-AMP的细胞内池.
- DasR可以调节伴侣HtpG,从而稳定DasR复合体,增强其DNA结合能力和在酸性压力下信号输出.
结论:
- c-di-AMP-DasR通路是一个多层调节网络,对Mycobacterium结核病酸适应和持久性至关重要.
- 这种途径将pH传感与转录重编程和伴侣介导稳定相结合,以获得强大的抗酸性.
- c-di-AMP-DasR轴代表了一个有前途的治疗标,以破坏Mycobacterium结核病的弹性.
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