Bacteriophage predation selects for diverse antiphage systems that frequently cluster on mobilizable defense islands in bacterial genomes. However, molecular insight into the reciprocal dynamics of phage-bacterial adaptations in nature is lacking, particularly in clinical contexts where there is need to inform phage therapy efforts and to understand how phages drive pathogen evolution. Using time-shift experiments, we uncovered fluctuations in Vibrio cholerae’s resistance to phages in clinical samples. We mapped phage resistance determinants to SXT integrative and conjugative elements (ICEs), which notoriously also confer antibiotic resistance. We found that SXT ICEs, which are widespread in γ-proteobacteria, invariably encode phage defense systems localized to a single hotspot of genetic exchange. We identified mechanisms that allow phage to counter SXT-mediated defense in clinical samples, and document the selection of a novel phage-encoded defense inhibitor. Phage infection stimulates high-frequency SXT ICE conjugation, leading to the concurrent dissemination of phage and antibiotic resistances.

噬菌体捕食选择不同的抗噬菌体系统，这些系统经常聚集在细菌基因组中可动员的防御岛上。然而，缺乏对自然界中噬菌体-细菌适应相互作用动力学的分子洞察，特别是在需要为噬菌体治疗工作提供信息和了解噬菌体如何驱动病原体进化的临床环境中。使用时移实验，我们发现了霍乱弧菌的波动对临床样本中的噬菌体的抗性。我们将噬菌体抗性决定因素映射到 SXT 整合和共轭元件 (ICE)，众所周知，这也赋予抗生素抗性。我们发现广泛存在于 γ-变形菌中的 SXT ICE 总是编码定位于单个遗传交换热点的噬菌体防御系统。我们确定了允许噬菌体在临床样本中对抗 SXT 介导的防御的机制，并记录了一种新型噬菌体编码防御抑制剂的选择。噬菌体感染刺激高频 SXT ICE 结合，导致噬菌体和抗生素耐药性的同时传播。