Bacterial biodiversity drives the evolution of CRISPR-based phage resistance
Bacterial biodiversity drives the evolution of CRISPR-based phage resistance
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DOI：
10.1038/s41586-019-1662-9
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发表时间：
2019-10-24
期刊：
影响因子：
64.8
通讯作者：
Westra, Edze R.
中科院分区：
文献类型：
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作者：
Alseth, Ellinor O.;Pursey, Elizabeth;Westra, Edze R.
大约一半的细菌携带CRISPR-Cas适应性免疫系统的基因（1），该系统通过将来自噬菌体和其他寄生DNA元件的短DNA序列插入宿主基因组上的CRISPR基因座来提供免疫记忆（2）。尽管CRISPR基因座在自然环境中迅速进化（3，4），但细菌物种通常在实验室条件下通过噬菌体受体的突变或丧失而进化噬菌体抗性（5，6）。在这里，我们报告了这种差异如何部分解释为体外和自然环境中生物复杂性的差异（7，8）。具体来说，通过使用机会致病菌铜绿假单胞菌及其噬菌体DMS 3vir，我们表明与其他人类病原体的共存放大了与噬菌体受体突变相关的适应性权衡，因此有利于基于CRISPR的抗性的进化。我们还证明，这对铜绿假单胞菌的毒力具有重要的连锁效应，只有当细菌进化出基于表面的耐药性时，铜绿假单胞菌的毒力才会减弱。我们的数据表明，自然环境中微生物群落的生物复杂性是CRISPR-Cas适应性免疫进化的重要驱动力，对细菌适应性和毒力具有关键影响。
About half of all bacteria carry genes for CRISPR-Cas adaptive immune systems(1), which provide immunological memory by inserting short DNA sequences from phage and other parasitic DNA elements into CRISPR loci on the host genome(2). Whereas CRISPR loci evolve rapidly in natural environments(3,4), bacterial species typically evolve phage resistance by the mutation or loss of phage receptors under laboratory conditions(5,6). Here we report how this discrepancy may in part be explained by differences in the biotic complexity of in vitro and natural environments(7,8). Specifically, by using the opportunistic pathogen Pseudomonas aeruginosa and its phage DMS3vir, we show that coexistence with other human pathogens amplifies the fitness trade-offs associated with the mutation of phage receptors, and therefore tips the balance in favour of the evolution of CRISPR-based resistance. We also demonstrate that this has important knock-on effects for the virulence of P. aeruginosa, which became attenuated only if the bacteria evolved surface-based resistance. Our data reveal that the biotic complexity of microbial communities in natural environments is an important driver of the evolution of CRISPR-Cas adaptive immunity, with key implications for bacterial fitness and virulence.