通过糖酸盐介导,抑制了酸糖前体合成的过程
Megan R Keller1,2, Vijay Soni3, Megan Brown3
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
缺乏葡萄糖-6-酸盐异构酶 (Δpgi) 的Vibrio cholerae中的葡萄糖毒性源于抑制的GlmU,影响细胞壁合成和抗生素耐药性. N-乙葡萄糖胺可以挽救这些效应.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 抗生素耐受性是抗生素耐药性的前体,但仍未得到充分研究.
- 胆杆菌是一种格拉姆阴性病原体,对β-乳酸抗生素具有很高的耐受性.
- 通过pgi删除扰乱V. cholerae中的糖解会增加由于细胞壁损伤而对β-乳酸盐的敏感性.
研究的目的:
- 阐明细胞壁损伤和抗生素敏感性背后的机制 Δpgi V. cholerae 暴露于葡萄糖.
- 为了确定分子点和途径,在这种突变体中调解葡萄糖毒性.
主要方法:
- 在葡萄糖和各种补充剂的存在下种植的Dpgi V. cholerae的表型分析.
- 有针对性的代谢学,以确定关键的代谢中间体和酶活性.
- 在体外酶测试中,描述了GlmU和糖酸盐之间的相互作用.
主要成果:
- 葡萄糖导致增长抑制,溶解和细胞外损伤在dpgi V. cholerae.
- 补充N-乙葡萄糖胺可以挽救暴露在葡萄糖中的Δpgi突变体的生长,抗生素耐药性和细胞形态.
- 酶GlmU作为一个关键的瓶;葡萄糖-1-酸盐抑制了GlmU的活性,损害了甘油 (PG) 和脂多糖 (LPS) 生物合成.
结论:
- GlmU 是一个关键的酶,将中央新陈代谢与V. cholerae中的细胞包膜完整性联系起来.
- 在Δpgi突变中的葡萄糖毒性是由GlmU抑制的介导,导致细胞壁合成受损,并增加对β-乳酸盐的敏感性.
- 准GlmU或相关途径可能为打击V. cholerae感染提供新的策略.
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