亚利碳化合物受体和FOS调解由Acinetobacter baumannii诱导的细胞毒性
Chun Kew1,2, Cristian Prieto-Garcia1, Anshu Bhattacharya1,2
1Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt, Germany.
Nature communications
|September 11, 2024
概括
Acinetobacter baumannii感染诱导宿主转录因子FOS,增加细胞损伤. 抑制FOS或阻断基碳化合物受体 (AHR) 途径可以降低模型中的细菌细胞毒性.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 宝曼尼菌 (Acinetobacter baumannii) 是一种多药耐药的病原体,导致严重的医院感染.
- 了解其致病机制对于开发有效的治疗方法至关重要.
研究的目的:
- 在蛋白质层面阐明宿主对A. baumannii感染的反应.
- 为了识别导致细菌病变的宿主因素.
- 为了研究素受体 (AHR) 途径在A. baumannii感染中的作用.
主要方法:
- 对受感染和未受感染的人类细胞进行比较蛋白质组分析.
- 药理上抑制宿主转录因子FOS.
- 基于细胞的体外模型和体内小鼠感染模型.
- 研究A. baumannii外膜囊泡 (OMVs) 与宿主细胞的相互作用.
- 细菌成分对AHR通路激活的分析.
主要成果:
- 转录因子FOS被确定为A. baumannii感染期间最容易诱导的宿主蛋白.
- 在细胞和小鼠模型中,抑制FOS显著降低了细菌细胞毒性.
- A. baumannii外膜囊泡通过诱导二二氧化酶 (TDO) 来激活宿主AHR通路.
- AHR激活导致FOS基因转录,促进宿主细胞细胞毒性.
结论:
- 曼尼菌感染会破坏宿主托的代谢.
- AHR-FOS信号轴在调解细菌诱导的宿主细胞细胞毒性方面发挥着关键作用.
- 准AHR-FOS通路为对抗A. baumannii感染提供了一个潜在的治疗策略.
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