Diversity in CRISPR-based immunity protects susceptible genotypes by restricting phage spread and evolution

Diversity in CRISPR-based immunity protects susceptible genotypes by restricting phage spread and evolution
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基于 CRISPR 的免疫多样性通过限制噬菌体传播和进化来保护易感基因型

DOI:
10.1101/774349
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发表时间:
2019
期刊:
--
影响因子:
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通讯作者:
Common J
Common J
中科院分区:
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文献类型:
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作者:
Common J

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2寄主抗性的多样性往往与病原菌传播的减少有关。这3可能是由于病原体进化的限制,以及由于焦点宿主的稀释而导致病原体繁殖4的减少。细菌-噬菌体5相互作用的理论和实验表明,细菌适应性免疫系统的遗传多样性可以限制噬菌体进化以克服耐药性。在这里,我们探索免疫多样性如何影响噬菌体的传播,当他们能够克服抗性8等位基因时,以及免疫多样性是否影响噬菌体的进化以增加其宿主范围。我们发现,更高的多样性通过限制噬菌体的传播使敏感和耐药细菌都受益,这与噬菌体获得进一步突变以克服其他抗性等位基因的可能性降低有关。12这些数据突出了宿主抗性等位基因多样性的流行病学和进化后果与其对14种宿主-病原体相互作用的关键后果之间的密切联系。15个
2 Diversity in host resistance often associates with reduced pathogen spread. This 3 may result from limitation of pathogen evolution, and reduced pathogen reproduction 4 due to the dilution of focal hosts. Theory and experiments on bacteria-phage 5 interactions have shown that genetic diversity of the bacterial adaptive immune 6 system can limit phage evolution to overcome resistance. Here we explore how 7 immune diversity impacts the spread of phage when they can overcome a resistance 8 allele, and whether immune diversity affects the evolution of the phage to increase 9 its host range. We show that higher diversity benefits both susceptible and resistant 10 bacteria by limiting the spread of the phage, and this is linked to a reduced 11 probability that phage acquire further mutations to overcome other resistance alleles. 12 These data highlight the tight link between the epidemiological and evolutionary 13 consequences of host resistance allele diversity and their key consequences for 14 host-pathogen interactions. 15