Temporal shifts in antibiotic resistance elements govern phage-pathogen conflicts

Bacteriophage predation selects for diverse anti-phage systems that frequently cluster on mobilizable defense islands in bacterial genomes. However, there remains a lack of molecular insight into the reciprocal dynamics of phage-bacterial adaptations in nature, particularly in clinical contexts where there is need to inform phage therapy efforts and understand how phages drive pathogen evolution. Here, Â we used time-shift assays to evaluate whether clinical Vibrio cholerae isolates were susceptible to infection by phage from past, future or contemporaneous patient samples. Across a 34-month sampling period, we discover that phage resistance is governed by fluctuations in SXT integrative and conjugative elements (ICEs), which notoriously also confer antibiotic resistance. We further demonstrate potential trade-offs for having SXT ICEs, as we show they can also can restrict beneficial mobile genetic elements. We discover phage counter-adaptation to SXT-mediated restriction in clinical sam...