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 DNA^4,5; 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.

水平基因转移和突变是微生物进化的两个主要驱动力，使细菌能够适应波动的环境压力源¹。成簇的、规则间隔的短回文重复 (CRISPR) 系统使用 RNA 引导的核酸酶来指导对介导水平基因转移的移动遗传元件的基因组进行序列特异性破坏，例如结合质粒²和噬菌体³，从而限制了哪些细菌可以通过这种机制进化。CRISPR 系统的一个子集也表现出 DNA 的非特异性降解^4,5; 但是，尚未检查此功能是否以及如何影响主机。在这里，我们表明葡萄球菌 III-A 型 CRISPR-Cas 系统的非特异性 DNase 活性增加了宿主的突变并加速了金黄色葡萄球菌和表皮葡萄球菌中抗生素耐药性的产生。这些突变需要诱导对 DNA 损伤的 SOS 反应并显示出独特的模式。我们的研究结果表明，通过对产生遗传多样性的两种机制产生不同的影响，III-A 型 CRISPR 系统可以调节细菌宿主的进化。