Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Nat Commun. 2022 Apr 28;13(1):2296. doi: 10.1038/s41467-022-29919-9.
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.
抗微生物药物耐药性（AMR）的出现和传播是全球日益严重的医疗保健挑战。然而，形成这种抗药组的机制和时间尺度仍然难以捉摸。我们使用抗生素鸡尾酒对小鼠模型进行处理，并采用纵向采样策略，确定了肠道共生菌在单次抗生素疗程后获得抗微生物药物耐药基因（ARGs）的机制。虽然由于治疗大多数常驻细菌种群都被消耗殆尽，但 Akkermansia muciniphila 和肠杆菌科、肠球菌科和乳杆菌科的成员获得了耐药性并仍然具有抗性。我们在相应的宏基因组组装基因组（MAG）中确定了赋予对相应抗生素的抗性的特定基因，并追踪了它们在每个基因组中的起源。在这里，我们表明，虽然移动遗传元件（MGEs），包括噬菌体和质粒，有助于 ARG 的传播，但整合子是介导抗生素处理小鼠中 AMR 的关键因素。我们的研究结果表明，单次抗生素疗程可能单独作为选择压力，驱动肠道共生菌在单个哺乳动物寿命内获得 ARG 并发生耐药性。
