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PhoR传感器的双重功能是Mycobacterium结核病毒性的一个关键决定因素

Prabhat Ranjan Singh¹, Harsh Goar¹, Partha Paul¹

¹CSIR-Institute of Microbial Technology, Sector 39 A, Chandigarh, India.

|December 15, 2023

概括

结核菌PhoR感知酸性pH和高盐度,激活PhoP. 此外,PhoR还充当酸酶,形成一个对病毒性和巨细胞内的适应性至关重要的恒温系统.

科学领域:

微生物学微生物学
分子生物学分子生物学
结核病研究结核病研究

背景情况:

在Mycobacterium tuberculosis中,PhoP-PhoR双组分系统 (TCS) 对毒性和适应性至关重要.
了解PhoP-PhoR的信号和调节机制对于开发新的抗结核病疗法至关重要.

研究的目的:

为了识别PhoP-PhoR TCS检测到的环境信号.
阐明调节PhoP激活的机制及其下游效应.
调查PhoP-PhoR在M.结核病毒性和宿主适应中的作用.

主要方法:

酸化试验用于研究PhoP激活.
转录组分析以确定PhoP regulon基因.
全基因组相互作用查以识别新型激酶.
位点定向的突变发生,以确定PhoR中的功能性动机.

主要成果:

PhoR作为酸性pH和高盐度条件的传感器,导致PhoP酸化.
确定了一种非正规的PhoP激活途径,涉及传感器激酶PrrB.
PhoR表现出双酶和酸酶活性,调节P~PhoP水平.
在巨细胞和动物模型中,PhoR删除显著减弱了M.结核病.

结论:

PhoR是M.结核菌适应低pH环境的关键调节剂,特别是在巨细胞的虫体内.
PhoR的双酶/酶活性建立了P~PhoP调节的恒常机制.
针对PhoP-PhoR系统为开发新型抗结核病药物提供了一个有前途的战略.

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