ESI, Biosciences, University of Exeter, TR10 9FE Penryn, UK.
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow 143028, Russia.
Cell Host Microbe. 2022 Jan 12;30(1):31-40.e5. doi: 10.1016/j.chom.2021.11.014. Epub 2021 Dec 20.
Phages impose strong selection on bacteria to evolve resistance against viral predation. Bacteria can rapidly evolve phage resistance via receptor mutation or using their CRISPR-Cas adaptive immune systems. Acquisition of CRISPR immunity relies on the insertion of a phage-derived sequence into CRISPR arrays in the bacterial genome. Using Pseudomonas aeruginosa and its phage DMS3vir as a model, we demonstrate that conditions that reduce bacterial growth rates, such as exposure to bacteriostatic antibiotics (which inhibit cell growth without killing), promote the evolution of CRISPR immunity. We demonstrate that this is due to slower phage development under these conditions, which provides more time for cells to acquire phage-derived sequences and mount an immune response. Our data reveal that the speed of phage development is a key determinant of the evolution of CRISPR immunity and suggest that use of bacteriostatic antibiotics can trigger elevated levels of CRISPR immunity in human-associated and natural environments.
噬菌体对细菌施加强烈选择压力，促使其进化出抵抗病毒捕食的能力。细菌可以通过受体突变或利用 CRISPR-Cas 适应性免疫系统快速进化出噬菌体抗性。获得 CRISPR 免疫力依赖于将噬菌体衍生序列插入细菌基因组中的 CRISPR 阵列中。使用铜绿假单胞菌及其噬菌体 DMS3vir 作为模型，我们证明了降低细菌生长速率的条件，如暴露于抑菌抗生素（抑制细胞生长而不杀死细胞），可促进 CRISPR 免疫的进化。我们证明这是由于在这些条件下噬菌体的发育速度较慢，这为细胞获得噬菌体衍生序列和启动免疫反应提供了更多的时间。我们的数据表明，噬菌体的发育速度是 CRISPR 免疫进化的关键决定因素，并表明抑菌抗生素的使用可能会引发人类相关和自然环境中 CRISPR 免疫水平的升高。
