VapB抗毒素的酸化影响分子间相互作用,以调节Mycobacterium结核病中的VapC毒素活性
Basanti Malakar1,2, Valdir C Barth1,2, Julia Puffal3
1Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
Journal of bacteriology
|September 24, 2024
概括
在Mycobacterium tuberculosis中VapB抗毒素的酸化改变了它们与VapC毒素和DNA的相互作用. 这种可逆的修饰调节了VapC毒素的活性,影响了感染期间的细菌生存.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 细菌病原体的产生
背景情况:
- 毒素-抗毒素模块对于细菌病原体的生存至关重要,并且在Mycobacterium tuberculosis中非常丰富.
- VapBC毒素-抗毒素系统调节细菌细胞内毒素水平.
- 控制VapB-VapC相互作用和VapC毒性的机制尚不清楚.
研究的目的:
- 研究VapB蛋白酸化在调节VapB-VapC相互作用和Mycobacterium结核病中的VapC毒性的作用.
- 为了阐明VapB酸化对压制vapB-vapC操作子的影响.
主要方法:
- 用局部导向的突变发生法来创建相仿和可塑性VapB变体.
- 评估了VapB-VapC蛋白质与蛋白质的相互作用.
- 分析了VapB与促进体DNA的结合.
- 进行了Mycobacterium结核病增长抑制试验.
主要成果:
- 模仿VapB替代剂减少了VapB与相似的VapC毒素的相互作用,并减少了VapB与促进DNA的结合.
- 缩性VapB替代物没有显著改变VapB-VapC结合.
- VapB酸化调节了VapC的毒性,其中相仿性突变增加了毒性,而化突变降低了毒性.
结论:
- VapB抗毒素的Ser/Thr酸化代表了Mycobacterium tuberculosis中VapC毒素活性的一种新的调节机制.
- VapB化影响抗毒素与其同源毒素和促进者DNA结合.
- 这种调节机制可能对控制细菌毒素活动在感染期间响应宿主衍生的信号至关重要.
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