美国加州大学Kimberley D. Seed研究组发现抗生素抗性因素的时间变化控制着噬菌体-病原体的冲突。这一成果于2021年7月30日发表于国际一流学术期刊《科学》杂志上。

使用时移实验，他们发现了临床样本中霍乱弧菌对噬菌体抵抗力的波动。他们将噬菌体抗性决定因素映射到 SXT 整合和结合元件 (ICE)，众所周知，ICE 也赋予抗生素抗性。他们发现在γ-变形菌中广泛存在的 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。他们确定了允许噬菌体在临床样本中抵抗 SXT 介导的防御机制，并记录了新型噬菌体编码防御抑制子的选择。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。

研究人员表示，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的可移动防御岛上。然而，缺乏对自然界中噬菌体-细菌适应性相互动态的分子洞察，特别是在需要告知噬菌体治疗工作并了解噬菌体如何驱动病原体进化的临床环境中。

附：英文原文

Title: Temporal shifts in antibiotic resistance elements govern phage-pathogen conflicts

Author: Kristen N. LeGault, Stephanie G. Hays, Angus Angermeyer, Amelia C. McKitterick, Fatema-tuz Johura, Marzia Sultana, Tahmeed Ahmed, Munirul Alam, Kimberley D. Seed

Issue&Volume: 2021/07/30

Abstract: 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.

DOI: 10.1126/science.abg2166

Source: https://science.sciencemag.org/content/373/6554/eabg2166