Pp6-Pfkfb1轴通过调节宿主-病原体代谢交叉来调节细胞内细菌的增殖
Li Fan1, Yang Sun1, Fangzhou Lou1
1Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS pathogens
|December 31, 2025
概括
蛋白酸酶6 (Pp6) 调节宿主新陈代谢以控制沙门氏菌的复制. 准Pp6-Pfkfb1通路可以增强巨细胞对抗细胞内细菌病原体的抗菌防御能力.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 代谢过程中的代谢.
背景情况:
- 细胞内细菌病原体在宿主巨细胞内表现出不同的复制率.
- 病原体操纵宿主因子生存的机制尚未完全理解.
研究的目的:
- 调查蛋白质酸酶6 (Pp6) 在宿主对沙门氏菌Typhimurium感染的反应中的作用.
- 为了确定影响细菌生存的由Pp6调节的宿主因素.
主要方法:
- 在沙门氏菌感染的巨细胞中使用光稀释记者系统.
- 使用了Pp6和microRNA-31 (miR-31) 的条件淘汰模型.
- 进行了酵母双杂交选,以识别Pp6基质.
主要成果:
- 在复制沙门氏菌的巨细胞中,Pp6的下调.
- 缺少Pp6增加了对沙门氏菌的敏感性,损害了抗菌防御.
- miR-31 负调节了 Pp6;它的切除增强了细菌清除.
- 确定了6-果糖-2-激酶/果糖-2,6-双酸酶1 (Pfkfb1) 作为Pp6基质.
- 缺少Pp6增加了Pfkfb1的表达,通过氧化 (NO) 生产限制了沙门氏菌的生长,并抑制了阿尔金酶-1 (Arg-1).
结论:
- 在细胞内细菌感染期间,Pp6-Pfkfb1轴对宿主代谢适应至关重要.
- 这一途径调节了巨细胞的抗菌功能.
- Pp6-Pfkfb1轴代表了对抗多药耐药病原体的潜在治疗标.
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