对rRNA的Epitranscriptional m6A修改对Staphylococcus aureus的翻译和宿主殖民产生了负面影响
Kathryn E Shields1, David Ranava2, Yongjun Tan3
1Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.
PLoS pathogens
|January 22, 2024
概括
细菌23S rRNA由抗红红素甲基转移酶 (Erm) 的甲基化赋予了对MLS抗生素的交叉耐药性. 然而,这些修改后的核糖体损害了细菌的殖民和竞争力,这表明在翻译效率方面存在权衡.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 史诗转录组学 史诗转录组学
背景情况:
- 麦克罗利德,林科萨米德和链条蛋白B (MLS) 是重要的抗生素,但细菌耐药性,通常由Erm甲基转移酶介导,限制了它们的有效性.
- 埃尔姆酶在核酸A2058 (m6A2058) 中甲基化细菌23SrRNA,使其对MLS抗生素产生耐药性.
- 这种m6A表谱标记对核糖体功能和细菌生理学的功能后果在很大程度上是未知的.
研究的目的:
- 调查m6A2058修饰对黄金葡萄球菌核糖体功能,翻译忠实性和竞争适应性的影响.
- 阐明与超越抗生素耐药性的Erm介导的MLS耐药性相关的生理性权衡.
主要方法:
- 使用核糖体分析 (Ribo-Seq) 来分析m6A2058-修饰与未修饰核糖体的细菌的全球翻译模式.
- 采用双光记者系统来量化核糖体占用率和转化忠实度.
- 在体内进行了竞争性感染和殖民测试.
主要成果:
- 带有m6A2058-修饰核糖体的金黄色葡萄球菌菌株表现出受损的殖民化,并且在感染期间被未修饰核糖体的菌株超越.
- m6A2058核糖体的竞争劣势主要在抗生素压力下显而易见.
- 核糖体剖析揭示了参与宿主相互作用,新陈代谢和信息处理的基因不成比例的放松调节,这与转化能力和忠实度的降低有关.
结论:
- 虽然m6A2058表写体标记赋予了MLS抗性,但导致了一般的"无效翻译"表型.
- 这种低效的翻译影响了细菌的健康和竞争力,突出显示了对多药耐药细菌的重大权衡.
- 这些发现为抗生素耐药机制的生理成本提供了新的见解.
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