德拉姆1赋予了对沙门氏菌感染的抵抗力
Samrah Masud1, Jiajun Xie1, Bart J M Grijmans1
1Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Autophagy reports
|September 15, 2025
概括
调节DNA损伤自调节器1 (DRAM1) 通过增强LC3相关细胞 (LAP) 对沙门氏菌Typhimurium感染发挥宿主保护作用. 德拉姆1缺乏会影响细菌清除和宿主生存,而其过度表达会改善这些结果.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- LC3相关的细胞分裂 (LAP) 是一种与自相关的机制,向细胞内细菌.
- 在LAP中DRAM1 (DNA损伤调节自调节器1) 对抗沙门氏菌Typhimurium的作用尚不清楚.
- 巨细胞利用LAP在斑马鱼模型中限制沙门氏菌Typhimurium的生长.
研究的目的:
- 为了研究Dram1在LC3相关的细胞瘤 (LAP) 在沙门氏菌 Typhimurium感染期间的作用.
- 在斑马鱼感染模型中确定Dram1对宿主生存和细菌负担的影响.
- 阐明Dram1与诱导LAP和反应性氧物种 (ROS) 生产之间的功能联系.
主要方法:
- 使用斑马鱼模型对系统性沙门氏菌 Typhimurium 感染.
- 采用了morpholino knockdown和CRISPR/Cas9突变来评估Dram1的功能.
- 使用mRNA注射过度表达的Dram1.
- 量化细菌负担和宿主生存率.
- 评估了使用生物传感器菌株的GFP-LC3-Salmonella协会和ROS产量.
- 在小鼠RAW264.7巨细胞中验证的发现.
主要成果:
- 在S. Typhimurium感染期间,Dram1缺乏导致宿主生存率下降和细菌负担增加.
- Dram1过度表达缩短了沙门氏菌的复制和减少了宿主死亡率.
- 在Dram1缺乏的胚胎中,GFP-LC3-沙门氏菌的关联性减少,而在Dram1过度表达时,则增加.
- 德拉姆1缺乏消除了对沙门氏菌的ROS反应,而过度表达增强了它.
- 在小鼠巨细胞中观察到Dram1调节对LC3和ROS反应的类似效应.
结论:
- Dram1/DRAM1对抗沙门氏菌 Typhimurium 感染起着至关重要的宿主保护作用.
- 在功能上,Dram1/DRAM1与诱导LC3相关的细胞化 (LAP) 有关.
- 在沙门氏菌感染期间,Dram1/DRAM1调节菌体内的活性氧物种 (ROS) 反应.
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