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一个动态的CRISPR-Cas过度表达子群允许Streptococcus pyogenes快速响应菌体

Marie J Stoltzfus¹, Rachael E Workman¹, Nicholas C Keith¹

¹Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Nature microbiology

|July 12, 2024

概括

克里斯普尔-卡斯系统被抑制,但可以通过突变过度表达. 过度表达的细胞增强了菌体防御和记忆力,但减少了没有菌体的健康状况,这表明了细菌免疫的种群级策略.

科学领域:

微生物学微生物学
细菌免疫力细菌免疫力
基因规则基因规则

背景情况:

克里斯普尔-卡斯系统为细菌提供针对菌体的适应性免疫力.
在本地细菌宿主中,CRISPR-Cas表达通常被抑制.
在菌体感染期间诱导CRISPR-Cas表达的机制尚不清楚.

研究的目的:

在Streptococcus pyogenes中研究CRISPR-Cas表达的诱导.
描述具有CRISPR-Cas过度表达的特定细胞亚群的作用.
确定CRISPR-Cas过度表达对细菌健康和菌体防御的影响.

主要方法:

对具有影响Cas9结合tracr-L.L.的突变的Streptococcus pyogenes菌株的分析.
在野生类型和突变细胞中量化CRISPR-Cas表达水平.
在tracr-L目标部位的突变率的评估.
在过度表达与野生类型细胞中对菌体防御疗效和记忆形成的评估.

主要成果:

一个突变破坏Cas9结合的细胞亚群导致CRISPR-Cas过度表达.
通过增加突变率,Cas9积极促进这种过度表达子群的扩张.
克里斯普尔-卡斯过度表达者表现出增强的记忆形成和存储能力.
与野生类型细胞相比,过度表达增加了对菌体感染的抵抗力.
在缺乏菌体的情况下,CRISPR-Cas过度表达会降低细菌的适应性.

结论:

克里斯普尔-卡斯过度表达的细胞作为快速转录对菌体的反应的动态储库.
这种种群体水平的策略允许强大的菌体防御,而不会影响长期的个体细胞健康.
这些发现揭示了一种调节CRISPR-Cas免疫力和细菌适应的新机制.

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