Bacteriostatic antibiotics promote CRISPR-Cas adaptive immunity by enabling increased spacer acquisition

Bacteriostatic antibiotics promote CRISPR-Cas adaptive immunity by enabling increased spacer acquisition
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抗菌抗生素通过增加间隔区的获取促进CRISPR-CAS获得性免疫

DOI:
10.1016/j.chom.2021.11.014
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发表时间:
2022-01-12
影响因子:
30.3
通讯作者:
Westra, Edze R.
Westra, Edze R.
中科院分区:
医学1区
文献类型:
--
作者:
Dimitriu, Tatiana;Kurilovich, Elena;Westra, Edze R.

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噬菌体对细菌施加强选择以进化出对病毒捕食的抗性。细菌可以通过受体突变或使用其CRISPR-Cas适应性免疫系统快速进化噬菌体抗性。CRISPR免疫的获得依赖于将噬菌体衍生的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DMS 3vir作为模型,我们证明了降低细菌生长速率的条件,例如暴露于抑菌抗生素(抑制细胞生长而不杀死),促进了CRISPR免疫的进化。我们证明这是由于在这些条件下噬菌体发育较慢,这为细胞获得噬菌体衍生序列和产生免疫应答提供了更多的时间。我们的数据显示,噬菌体发育的速度是CRISPR免疫进化的关键决定因素,并表明使用抑菌抗生素可以在人类相关和自然环境中引发CRISPR免疫水平的提高。
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 phagederived 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.