Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus
Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus
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嗜热链球菌中 CRISPR-Cas 介导的耐药性的成本
DOI：
10.1098/rspb.2015.1270
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
S. Gandon
中科院分区：
文献类型：
--
作者：
P. Vale;Guillaume Lafforgue;François Gatchitch;R. Gardan;S. Moineau;S. Gandon
CRISPR-Cas 是微生物中适应性序列特异性免疫的一种形式。该系统为研究细菌与其病毒病原体、噬菌体之间的共同进化提供了独特的机会。要充分了解 CRISPR-Cas 的共同进化动力学，需要了解抵抗感染的成本的大小。在这里，使用革兰氏阳性细菌嗜热链球菌及其相关的剧毒噬菌体 2972（一个包含至少两个 II 型功能 CRISPR-Cas 系统的完善模型系统），我们根据隔离或成对竞争的生长测定获得了不同的适应性测量。我们测量了与这种适应性免疫系统的不同组成部分相关的适应性成本：Cas蛋白表达的成本、通过额外间隔区增加免疫记忆的组成成本，以及噬菌体暴露期间免疫的条件成本。我们发现 Cas 蛋白表达的成本特别高，因为 Cas 缺陷突变体比具有功能性 Cas 蛋白的野生型菌株获得了更高的竞争能力。通过获得多达四个噬菌体衍生的间隔区来增加免疫记忆与健身成本无关。此外，噬菌体暴露期间 CRISPR-Cas 系统的激活会导致显着但较小的适应成本。这些结果共同表明 CRISPR-Cas 系统的成本主要是由于防御系统的维护而产生的。我们讨论了这些结果对 CRISPR-Cas 介导的免疫进化的影响。
CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This system offers unique opportunities for the study of coevolution between bacteria and their viral pathogens, bacteriophages. A full understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost of resisting infection. Here, using the gram-positive bacterium Streptococcus thermophilus and its associated virulent phage 2972, a well-established model system harbouring at least two type II functional CRISPR-Cas systems, we obtained different fitness measures based on growth assays in isolation or in pairwise competition. We measured the fitness cost associated with different components of this adaptive immune system: the cost of Cas protein expression, the constitutive cost of increasing immune memory through additional spacers, and the conditional costs of immunity during phage exposure. We found that Cas protein expression is particularly costly, as Cas-deficient mutants achieved higher competitive abilities than the wild-type strain with functional Cas proteins. Increasing immune memory by acquiring up to four phage-derived spacers was not associated with fitness costs. In addition, the activation of the CRISPR-Cas system during phage exposure induces significant but small fitness costs. Together these results suggest that the costs of the CRISPR-Cas system arise mainly due to the maintenance of the defence system. We discuss the implications of these results for the evolution of CRISPR-Cas-mediated immunity.
影响因子：
11.4
作者：
Stern, Adi;Keren, Leeat;Wurtzel, Omri;Amitai, Gil;Sorek, Rotem
通讯作者：
Sorek, Rotem