菌核Rnf复合体的无活化减少了FadA介导的粉样蛋白形成和瘤发育
bioRxiv : the preprint server for biology
|April 28, 2025
概括
该Rnf复合体调节了FadA粘附处理在Fusobacterium核,影响结肠直肠癌 (CRC) 的发展. 这一发现揭示了一种新的代谢途径,影响细菌毒性和CRC瘤发生.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 菌核酸菌是一种口腔细菌,与结直肠癌 (CRC) 的进展有关.
- 在F. nucleatum表面的FadA粘附对CRC瘤发生至关重要.
- 呼吸系统酶Rnf复合物与F. nucleatum的毒性有关,但其确切的作用尚不清楚.
研究的目的:
- 研究Rnf复合体在调节Fada粘附蛋白中的作用及其对F. nucleatum在CRC中的毒性的影响.
- 阐明Rnf复合体影响FadA组合和粉样蛋白形成的分子机制.
- 了解Rnf复合体缺乏如何影响F. nucleatum侵入CRC细胞并促进瘤生长的能力.
主要方法:
- 在F. nucleatum.中Rnf复合体 (rnfC删除) 的遗传破坏.
- 对fadA转录水平和前体FadA (pFadA) 表达的分析.
- 研究响应调节器 (CarR,ArlR,S1) 和信号酶LepB在Fada处理中的作用.
- 评估细菌粘附,CRC细胞的入侵,以及体外球状瘤的形成.
主要成果:
- 破坏Rnf复合体显著降低了fadA转录水平和pFadA表达.
- Rnf复合体通过控制 LepB 表达的响应调节器 (CarR,ArlR,S1) 调节 FadA 处理.
- 缺乏Rnf复合体的F.核体显示FadA组合受损,粉样蛋白形成减少,CRC细胞的入侵减少.
- 虽然粘附不受影响,但Rnf缺乏的突变体显著减少了CRC细胞入侵和球状瘤形成.
结论:
- 该Rnf复合体通过涉及响应调节器和LepB的调节网络调节Fada粘附表达和CRC瘤发生.
- 这一途径对于FadA粉样蛋白的翻译后处理和表面组合至关重要,维持F. nucleatum的毒性.
- 针对Rnf复合体-LepB-FadA轴提供了一个潜在的策略来抑制F.核驱动的CRC进展.
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