黄金葡萄球菌的小非编码RNA IsrR调节TCA循环活动和毒性
Gustavo Rios-Delgado1, Aubrey K G McReynolds2, Emma A Pagella2
1Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ, 08901, USA.
bioRxiv : the preprint server for biology
|July 15, 2024
概括
黄金葡萄球菌使用毛皮来调节铁的吸收. 在isrRRNA中的突变通过影响依赖铁的酶和促进感染来帮助细菌生长.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 细菌病原体的产生
背景情况:
- 黄金葡萄球菌适应宿主缺乏铁的条件.
- 铁的吸收转录调节器 (Fur) 控制铁的稳态在黄金色.
- 铁的可用性影响细菌的新陈代谢和毒性.
研究的目的:
- 研究毛皮和调控RNAIsrR在S. aureus中铁代谢和毒性的作用.
- 阐明连接Fur,IsrR和依赖铁的酶的调节网络.
- 了解S. aureus在感染期间如何应对缺铁的情况.
主要方法:
- 生成和分析金黄色细菌删除突变体 (Δfur, ΔisrR).
- 使用转录分析评估基因表达 (acnA, sdhC, mqo, citZ, citM).
- 进行抑制剂分析以确定遗传相互作用.
- 进行体外结合测定和全细胞金属分析.
- 在小鼠感染模型中评估细菌生长和毒性.
主要成果:
- 一个 Δfur 突变体显示铁依赖性酸酶基因 (acnA) 的表达减少,损害了生长.
- 通过降低isrR转录,isrR (一种调节性RNA) 的突变恢复了Δfur突变体的生长.
- IsrR直接与acnA转录结合并影响其表达,以及其他TCA循环基因.
- 伊斯瑞增强铁的吸收和细胞内铁水平.
- 在皮肤和肺炎感染的小鼠模型中,Fur和IsrR都会导致S. aureus的毒性.
结论:
- IsrR作为转录后调节剂,影响铁的稳态和细菌的新陈代谢.
- Fur-IsrR调节轴对于S. aureus适应铁有限的环境和病原体产生至关重要.
- 针对这种监管途径可以提供针对黄金菌感染的新策略.
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