微生物脂多糖糖通过胰岛素/IGF-1信号调节宿主发育
1Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China.
International journal of molecular sciences
|August 14, 2025
概括
微生物脂多糖 (LPS) 作为发育线索,而不仅仅是一个免疫触发器. 大肠杆菌中LPS外核糖化酶的丧失导致了C. elegans的发育延迟,通过宿主营养感应通路进行介导.
科学领域:
- 微生物学 微生物学
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 来自格拉姆阴性细菌的脂聚糖 (LPS) 是通过托尔类受体4 (TLR4) 的已知免疫刺激剂.
- 它作为宿主生物体中的发育调节者的作用在很大程度上是未知的.
- 模型生物Caenorhabditis elegans为研究宿主微生物相互作用提供了遗传和 gnotobiotic 的优势.
研究的目的:
- 研究细菌脂多糖 (LPS) 作为宿主发育线索的尚未探索的功能.
- 为了确定影响宿主发育的LPS的特定细菌成分.
- 阐明介导LPS驱动的发育调节的宿主分子通路.
主要方法:
- 在Caenorhabditis elegans中对大肠杆菌LPS生物合成突变体的查.
- 评估宿主发育进展,以应对细菌突变.
- 研究使用外源性LPS和营养补充剂的救援机制.
- 分析宿主基因表达和信号通路,包括胰岛素/IGF-1信号通路.
主要成果:
- 一种缺乏外核糖化 (∆rfaG) 的特定大肠杆菌突变诱导了C. elegans的显著发育延迟.
- 这种发育迟缓独立于细菌代谢.
- 延迟是由外源性LPS和氨基酸补充剂拯救的,这表明LPS影响营养感应通路.
- 主体FOXO转录因子DAF-16,IIS的关键效应因子,调解了发育停止.
结论:
- 微生物LPS的功能是宿主发育的关键调节者,超出其已知的免疫作用.
- 主体胰岛素/IGF-1信号传导 (IIS) 途径,特别是DAF-16,是LPS诱导的发育效应的关键调解者.
- 这项研究揭示了一种新的宿主微生物交叉通话机制,其中细菌LPS充当发育信号.
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