(p) pGpp修改RNAP功能,以独立于丁糖的方式赋予β-乳糖抗性
Henri Voedts1, Constantin Anoyatis-Pelé1, Olivier Langella2
1Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France.
Nature microbiology
|March 5, 2024
概括
升高的 (p) pGpp水平会导致β-乳酸盐耐药性,但不会改变丁糖的新陈代谢. 在RNA聚合酶和核糖体功能的修改是防止β-乳糖酶关键酶的失活的关键.
科学领域:
- 细菌生理学 细菌生理学
- 分子生物学分子生物学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 警报激素 (p) pGpp 调节细菌对营养压力的反应.
- 升高的 (p) pGpp水平与梅西林和广谱β-乳酸耐药性有关,特别是通过β-乳酸不敏感的转酶YcbB (LdtD).
研究的目的:
- 调查 (p)ppGpp在调节细菌细胞壁丁糖的新陈代谢中对beta-lactam耐药性的潜在作用.
- 阐明背后的机制 (p) p Gpp介导的β-乳酸盐耐药性.
主要方法:
- 使用高分辨率质谱测量分析大肠杆菌酸糖的结构.
- 基因操纵包括RNA聚合酶 (RNAP) 子单元中的氨基酸替代和CRISPR干扰 (CRISPRi) 进行核糖体RNA操作子下调.
主要成果:
- 证实 (p) pGpp依赖的β-乳酸盐耐药性不涉及酸甘油代谢的改变.
- 在RNAP子单元中的特定氨基酸替代,有或没有核糖体RNA操作子下调,赋予了耐药性.
- 发现β-乳糖胺对RNAP或核糖体没有直接影响.
结论:
- 由 (p)ppGpp介导的β-乳酸盐耐药性独立于酸甘油代谢的变化.
- 在RNA聚合酶和核糖体功能的修改对于防止β-乳糖胺对糖转酶的有害影响至关重要.
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