Parasite–host co-evolution results in population extinction or co-existence, yet the factors driving these distinct outcomes remain elusive. In this study, Salmonella strains were individually co-evolved with the lytic phage SF1 for 30 days, resulting in phage extinction or co-existence. We conducted a systematic investigation into the phenotypic and genetic dynamics of evolved host cells and phages to elucidate the evolutionary mechanisms. Throughout co-evolution, host cells displayed diverse phage resistance patterns: sensitivity, partial resistance, and complete resistance, to wild-type phage. Moreover, phage resistance strength showed a robust linear correlation with phage adsorption, suggesting that surface modification-mediated phage attachment predominates as the resistance mechanism in evolved bacterial populations. Additionally, bacterial isolates eliminating phages exhibited higher mutation rates and lower fitness costs in developing resistance compared to those leading to co-existence. Phage resistance genes were classified into two categories: key mutations, characterized by nonsense/frameshift mutations in rfaH-regulated rfb genes, leading to the removal of the receptor O-antigen; and secondary mutations, which involve less critical modifications, such as fimbrial synthesis and tRNA modification. The accumulation of secondary mutations resulted in partial and complete resistance, which could be overcome by evolved phages, whereas key mutations conferred undefeatable complete resistance by deleting receptors. In conclusion, higher key mutation frequencies with lower fitness costs promised strong resistance and eventual phage extinction, whereas deficiencies in fitness cost, mutation rate, and key mutation led to co-existence. Our findings reveal the distinct population dynamics and evolutionary trade-offs of phage resistance during co-evolution, thereby deepening our understanding of microbial interactions.

中文翻译：

---

受体修饰和适应性之间的权衡驱动宿主-噬菌体共进化，导致噬菌体灭绝或共存


寄生虫与宿主的共同进化导致种群灭绝或共存，但驱动这些不同结果的因素仍然难以捉摸。在这项研究中，沙门氏菌菌株与裂解噬菌体 SF1 单独共进化 30 天，导致噬菌体灭绝或共存。我们对进化的宿主细胞和噬菌体的表型和遗传动力学进行了系统研究，以阐明进化机制。在整个协同进化过程中，宿主细胞表现出不同的噬菌体抗性模式：对野生型噬菌体的敏感性、部分耐药性和完全耐药性。此外，噬菌体抗性强度与噬菌体吸附表现出强大的线性相关性，表明表面修饰介导的噬菌体附着是进化细菌种群中的主要抗性机制。此外，与导致共存的细菌分离株相比，消除噬菌体的细菌分离株在产生耐药性方面表现出更高的突变率和更低的适应成本。噬菌体抗性基因分为两类：关键突变，其特征是 rfaH 调节的 rfb 基因中的无义/移码突变，导致受体 O 抗原的去除;和继发突变，涉及不太关键的修饰，例如菌毛合成和 tRNA 修饰。次生突变的积累导致部分和完全耐药性，这可以通过进化的噬菌体来克服，而关键突变通过删除受体赋予不可战胜的完全耐药性。总之，较高的关键突变频率和较低的适应成本预示着强大的抗性并最终导致噬菌体灭绝，而适应成本、突变率和关键突变的缺陷导致了共存。 我们的研究结果揭示了协同进化过程中噬菌体抗性的不同种群动力学和进化权衡，从而加深了我们对微生物相互作用的理解。