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Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction–modification and CRISPR-Cas

机译:为什么在有抗药性时忍受免疫力:对种群的游览以及限制性修饰和CRISPR-Cas的进化动力学

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摘要

Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction–modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
机译:细菌很容易产生阻止噬菌体(噬菌体)吸附的突变,从而使细菌对这些病毒的感染具有抵抗力。然而,大多数细菌携带复杂的先天和/或适应性免疫系统:分别是限制性修饰(RM)和CRISPR-Cas。通常认为RM和CRISPR-Cas都已进化并保持其功能,以保护细菌免于因溶菌噬菌体感染而死。使用数学模型和计算机模拟,我们探索了溶菌噬菌体介导的选择将有利于这种复杂的先天和适应性免疫系统而不是简单的包膜抗性的条件。我们的分析结果表明,当细菌种群面临裂解性噬菌体时:(i)在缺乏免疫力的情况下,即使是多种具有独立受体的噬菌体,其抵抗力也很容易演变。 (ii)RM免疫可通过防止噬菌体入侵已建立的细菌种群而使细菌受益,尤其是当存在多个噬菌体物种吸附到不同受体时。 (iii)CRISPR-Cas免疫是否会胜过包膜抗性,关键取决于细菌间隔区和产生噬菌体的CRISPR-逃逸突变体之间的协同进化军备竞赛的步数。我们在RM和CRISPR-Cas进化和维持的背景下讨论了这些结果的含义,并强调了尚未解决的基本问题。本文是讨论会议议题``原核CRISPR-Cas适应性免疫的生态学和进化''的一部分系统”。

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