摘要
      抗微生物耐药性（AMR）的出现和传播代表着全球范围内日益增长的医疗保健挑战。然而，形成这种抵抗的机制和时间尺度仍然难以捉摸。使用对小鼠模型施用的抗生素混合物以及纵向采样策略，我们确定了肠道共生菌在单一抗生素疗程后获得抗微生物耐药性基因（ARGs）的机制。虽然大多数常驻细菌种群因治疗而耗尽，但粘氏阿克曼菌和肠杆菌科、肠球菌科和乳杆菌科的成员会产生耐药性，并保持顽固性。我们在相应的宏基因组组装基因组（MAG）中鉴定了赋予抗生素耐药性的特定基因，并追踪了它们在每个基因组中的起源。在这里，我们发现，虽然包括噬菌体和质粒在内的可移动遗传元件（MGE）有助于ARGs的传播，但整合子是抗生素治疗小鼠中介导AMR的关键因素。我们的研究结果表明，在哺乳动物的一个生命周期内，单用一个疗程的抗生素就可能作为选择性扫描驱动ARG的获取和肠道共生的发生率。
Abstract
The emergence and spread of antimicrobial resistance (AMR) represent an ever-growing healthcare challenge worldwide. Nevertheless, the mechanisms and timescales shaping this resistome remain elusive. Using an antibiotic cocktail administered to a murine model along with a longitudinal sampling strategy, we identify the mechanisms by which gut commensals acquire antimicrobial resistance genes (ARGs) after a single antibiotic course. While most of the resident bacterial populations are depleted due to the treatment, Akkermansia muciniphila and members of the Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae families acquire resistance and remain recalcitrant. We identify specific genes conferring resistance against the antibiotics in the corresponding metagenome-assembled genomes (MAGs) and trace their origins within each genome. Here we show that, while mobile genetic elements (MGEs), including bacteriophages and plasmids, contribute to the spread of ARGs, integrons represent key factors mediating AMR in the antibiotic-treated mice. Our findings suggest that a single course of antibiotics alone may act as the selective sweep driving ARG acquisition and incidence in gut commensals over a single mammalian lifespan.

https://www.nature.com/articles/s41467-022-29919-9