基于LiaS的MadR regulon激活使Enterococcus faecalis细胞外防御系统之间的交叉对话成为可能
Kara S Hood1, Samie A Rizvi1, Guillermo A Hoppe-Elsholz1,2
1Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
肠球菌利用相互连接的细胞外信号系统,LiaFSR和MadRS,对抗微生物和抗生素 (如达普托) 进行生存. 在LiaS和MadR之间进行交叉调节,使得MadR调节子能够独立于MadS信号的表达.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 分子生物学分子生物学
背景情况:
- 肠杆菌,常见的肠道细菌,面临着来自宿主抗菌和微生物群的持续威胁.
- 利雅FSR和MadRS两组系统对于抗击这些挑战的肠球菌生存至关重要,包括像达普素这样的抗生素.
- 这些系统涉及控制基因表达的丁激酶 (LiaS,MadS) 和响应调节器 (LiaR,MadR).
研究的目的:
- 研究Enterococcus faecalis.中的LiaFSR和MadRS信号系统之间的相互作用.
- 阐明控制细菌在抗微生物和daptomycin的存在下生存的调节机制.
- 确定LiaS和MadR之间的交叉调节在激活MadR调节中的作用.
主要方法:
- 构建和分析Enterococcus faecalis. 的同位素删除菌株.
- 确定达普托米辛最小抑制度 (MICs).
- 在MadR regulon中对关键基因的转录分析.
- 微尺度热泳以评估蛋白质 - 连接体结合亲缘关系.
主要成果:
- 删除突变体表现出不同的达普素敏感性,OG1RFΔmadR表现出增加的敏感性,OG1RFΔmadS表现出降低的敏感性.
- 包括madG,madL和dltA在内的MadR regulon在OG1RFΔmadS背景下显示了达普素依赖的上调调节,这表明LiaFSR系统参与其中.
- 利雅S对利雅R和马德R都表现出结合亲和力,而马德S则优先结合马德R,这表明潜在的跨监管相互作用.
结论:
- MadR regulon可以独立于MadS信号通路被激活,可能是通过LiaS和MadR之间的交叉通话.
- 肠球菌具有相互连接的细胞外信号网络,增强了对抗生素和抗菌的生存能力.
- 这种复杂的信号网络是肠球菌在充满挑战的环境中的适应能力的关键.
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