反抗性转录因子EspM和EspN调节M中的ESX-1分泌系统. 马里 (marinum) 是一个
Kathleen R Nicholson1, Rachel M Cronin1, Rebecca J Prest1
1Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA.
mBio
|March 6, 2024
概括
我们确定了EspN,一种控制病原菌菌中ESX-1分泌系统的转录因子. 在巨和斑马鱼感染期间,EspN对于毒性至关重要,这揭示了这一关键细菌通路的新调节层.
科学领域:
- 微生物学和分子病原发生学
- 细菌蛋白质分泌系统 细菌蛋白质分泌系统
- 菌根细菌病毒性因素 菌根细菌病毒性因素
背景情况:
- 致病性菌根细菌利用分泌系统,如ESX-1,用于毒性和宿主相互作用.
- ESX-1系统对于破坏宿主细胞防御和使细胞质进入成为可能至关重要.
- 现有的调节器EspM和WhiB6不能完全解释ESX-1在感染期间的基因调节.
研究的目的:
- 在致病性菌根细菌中识别ESX-1分泌系统的新型调节剂.
- 阐明这些调节剂在细菌病原和宿主细胞相互作用中的作用.
- 了解转录控制与ESX-1系统功能之间的相互作用.
主要方法:
- 对#Mycobacterium marinum*进行基因操纵,以删除或突变关键的调节基因.
- 使用转录分析评估细菌基因表达.
- 在体外巨细胞感染测试评估细菌存活率和细胞分解.
- 在体内斑马鱼幼虫感染模型,以确定疾病负担.
主要成果:
- 确定 EspN 作为一个关键的转录因子,此前被 EspM 抑制剂掩盖.
- 在实验室和感染条件下,EspN激活*whiB6*和ESX-1基因的转录.
- 对于 *M. marinum* 巨细胞的生长,细胞分解和斑马鱼疾病的进展,独立地需要 EspN.
结论:
- EspN 和 EspM 协调调节 ESX-1 系统,影响菌根菌病原性.
- 虽然EspN控制了一条主要的毒性通路,对感染至关重要,但它的作用在标准实验室条件下是掩盖的.
- 这一发现突出了一个关键的,但以前未被识别的,调节菌根杆菌毒性的调节器.
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