Diversity in host resistance often associates with reduced pathogen spread. This may result from ecological and evolutionary processes, likely with feedback between them. Theory and experiments on bacteria-phage interactions have shown that genetic diversity of the bacterial adaptive immune system can limit phage evolution to overcome resistance. Using the CRISPR-Cas bacterial immune system and lytic phage, we engineered a host-pathogen system where each bacterial host genotype could be infected by only one phage genotype. With this model system, we explored how CRISPR diversity impacts the spread of phage when they can overcome a resistance allele, how immune diversity affects the evolution of the phage to increase its host range, and if there was feedback between these processes. We show that increasing CRISPR diversity benefits susceptible bacteria via a dilution effect, which limits the spread of the phage. We suggest that this ecological effect impacts the evolution of novel phage genotypes, which then feeds back into phage population dynamics.

中文翻译：

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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


宿主抵抗力的多样性通常与病原体传播的减少有关。这可能是生态和进化过程的结果，很可能是它们之间的反馈。细菌-噬菌体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。利用 CRISPR-Cas 细菌免疫系统和裂解噬菌体，我们设计了一种宿主-病原体系统，其中每种细菌宿主基因型只能被一种噬菌体基因型感染。通过这个模型系统，我们探索了当噬菌体能够克服抗性等位基因时，CRISPR多样性如何影响噬菌体的传播，免疫多样性如何影响噬菌体的进化以增加其宿主范围，以及这些过程之间是否存在反馈。我们表明，增加 CRISPR 多样性通过稀释效应有利于易感细菌，从而限制了噬菌体的传播。我们认为这种生态效应会影响新噬菌体基因型的进化，然后反馈到噬菌体种群动态中。