美国洛克菲勒大学Luciano A. Marraffini、Charlie Y. Mo等研究人员合作发现，III-A型CRISPR免疫促进葡萄球菌突变。 这一研究成果于2021年4月7日在线发表在国际学术期刊《自然》上。

研究人员发现，金黄色葡萄球菌和表皮葡萄球菌的III-A型葡萄球菌CRISPR-Cas系统的非特异性DNA酶活性增加了宿主中的突变并加速了抗生素耐药性的产生。这些突变需要诱导SOS对DNA损伤的反应，并表现出独特的模式。这些结果表明，通过差异地影响产生遗传多样性的两种机制，III-A型CRISPR系统可以调节细菌宿主的进化。

据了解，水平基因转移和突变是微生物进化的两个主要驱动力，这使得细菌能够适应不断变化的环境压力。CRISPR系统使用RNA引导的核酸酶介导水平基因转移可移动遗传元件（例如结合质粒和噬菌体）的基因组序列特异性破坏，从而限制了细菌通过这种机制进化的程度。CRISPR系统的一个亚群也表现出DNA的非特异性降解。但是，尚未研究此功能是否以及如何影响宿主。

附：英文原文

Title: Type III-A CRISPR immunity promotes mutagenesis of staphylococci

Author: Charlie Y. Mo, Jacob Mathai, Jakob T. Rostl, Andrew Varble, Dalton V. Banh, Luciano A. Marraffini

Issue&Volume: 2021-04-07

Abstract: Horizontal gene transfer and mutation are the two major drivers of microbial evolution that enable bacteria to adapt to fluctuating environmental stressors1. Clustered, regularly interspaced, short palindromic repeats (CRISPR) systems use RNA-guided nucleases to direct sequence-specific destruction of the genomes of mobile genetic elements that mediate horizontal gene transfer, such as conjugative plasmids2 and bacteriophages3, thus limiting the extent to which bacteria can evolve by this mechanism. A subset of CRISPR systems also exhibit non-specific degradation of DNA4,5; however, whether and how this feature affects the host has not yet been examined. Here we show that the non-specific DNase activity of the staphylococcal type III-A CRISPR–Cas system increases mutations in the host and accelerates the generation of antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. These mutations require the induction of the SOS response to DNA damage and display a distinct pattern. Our results demonstrate that by differentially affecting both mechanisms that generate genetic diversity, type III-A CRISPR systems can modulate the evolution of the bacterial host.

DOI: 10.1038/s41586-021-03440-3

Source: https://www.nature.com/articles/s41586-021-03440-3