摘要
      抗生素过度消耗是抗生素耐药性（AMR）和抗生素耐药性细菌（ARB）出现的直接原因，尽管其对环境的影响尚不清楚。迫切需要剖析ARB及其在医院污水中的抗性和移动性动态共同进化的复杂联系。采用宏基因组和生物信息学方法，结合从三级护理医院收集的临床抗生素使用数据，分析医院污水中的微生物群落、耐药性和流动性。在本研究中，鉴定了耐药组（1568个抗生素耐药基因，ARGs，对应29种抗生素类型/亚型）和移动组（247种类型的移动遗传元件，MGE）。连接共存ARG和MGE的网络包括176个节点和578条边，其中超过19种类型的ARG与MGE具有显著相关性。处方剂量和时间依赖性抗生素消耗与ARGs的丰度和分布以及ARGs通过MGE的偶联转移有关。变异划分分析表明，偶联转移的影响很可能是AMR瞬时传播和持续的主要因素。我们提出了第一个证据支持这样一种观点，即临床抗生素的使用是共同进化的耐药性和移动性的强大驱动力，这反过来又支持ARB在医院污水中的生长和进化。临床抗生素的使用要求在抗生素管理和管理方面给予更多的关注。
Abstract
Overconsumption of antibiotics is an immediate cause for the emergence of antimicrobial resistance (AMR) and antibiotic resistant bacteria (ARB), though its environmental impact remains inadequately clarified. There is an urgent need to dissect the complex links underpinning the dynamic co-evolution of ARB and their resistome and mobilome in hospital sewage. Metagenomic and bioinformatic methods were employed to analyze the microbial community, resistome and mobilome in hospital sewage, in relation to data on clinical antibiotic use collected from a tertiary-care hospital. In this study, resistome (1,568 antibiotic resistance genes, ARGs, corresponding to 29 antibiotic types/subtypes) and mobilome (247 types of mobile genetic elements, MGEs) were identified. Networks connecting co-occurring ARGs with MGEs encompass 176 nodes and 578 edges, in which over 19 types of ARGs had significant correlations with MGEs. Prescribed dosage and time-dependent antibiotic consumption were associated with the abundance and distributions of ARGs, and conjugative transfer of ARGs via MGEs. Variation partitioning analyses show that effects of conjugative transfer were most likely the main contributors to transient propagation and persistence of AMR. We have presented the first evidence supporting idea that use of clinical antibiotics is a potent driving force for the development of co-evolving resistome and mobilome, which in turn supports the growth and evolution of ARB in hospital sewage. The use of clinical antibiotics calls for greater attention in antibiotic stewardship and management.

https://www.sciencedirect.com/science/article/abs/pii/S0269749123005419