摘要
出身背景
我们相互关联的世界和细菌快速交换抗生素耐药性基因（ARGs）的能力使得在“一个健康”框架下建立废水处理厂（WWTP）和人类/动物相关细菌之间的多药耐药性（MDR）转移的流行病学联系尤为重要。然而，ARGs交换的证据和促成这种转移的潜在因素仍然有限。
后果
在这里，通过将基于培养的群体基因组学和遗传比较与公开可用的数据集相结合，我们重建了82个污水处理厂耐多药分离株的完整基因组，发现大多数污水处理厂相关分离株在基因上与其目前在公共数据库中可用的最接近的人类/动物相关亲属不同。即使在少数亲缘关系密切的谱系中，污水处理厂相关分离株的质粒组成也截然不同。我们鉴定了高多样性的环状质粒（共264个，其中141个可能是新的），这是耐药性的主要来源，并显示了携带ARG的质粒在污水处理厂和人类/动物相关细菌之间的潜在水平转移。值得注意的是，具有不同遗传背景的潜在转移的ARGs和毒力因子（VFs）与侧翼插入序列（IS）密切相关，这表明质粒和IS之间的协同作用在介导MDR的多层分级转移和促进MDR高毒力克隆的出现方面的重要性。
结论
我们的发现推动了目前在污水处理厂和人类/动物相关细菌之间建立耐多药传播潜在流行病学联系的努力。质粒在介导ARGs的转移中发挥着重要作用，应优先考虑偶联质粒携带的IS相关ARGs，以应对耐药性的传播。
Abstract
Background
Our interconnected world and the ability of bacteria to quickly swap antibiotic resistance genes (ARGs) make it particularly important to establish the epidemiological links of multidrug resistance (MDR) transfer between wastewater treatment plant (WWTP)- and human/animal-associated bacteria, under the One Health framework. However, evidence of ARGs exchange and potential factors that contribute to this transfer remain limited.

Results
Here, by combining culture-based population genomics and genetic comparisons with publicly available datasets, we reconstructed the complete genomes of 82 multidrug-resistant isolates from WWTPs and found that most WWTP-associated isolates were genetically distinct from their closest human/animal-associated relatives currently available in the public database. Even in the minority of lineages that were closely related, WWTP-associated isolates were characterized by quite different plasmid compositions. We identified a high diversity of circular plasmids (264 in total, of which 141 were potentially novel), which served as the main source of resistance, and showed potential horizontal transfer of ARG-bearing plasmids between WWTP- and humans/animal-associated bacteria. Notably, the potentially transferred ARGs and virulence factors (VFs) with different genetic backgrounds were closely associated with flanking insertion sequences (ISs), suggesting the importance of synergy between plasmids and ISs in mediating a multilayered hierarchical transfer of MDR and potentiating the emergence of MDR-hypervirulent clones.

Conclusion
Our findings advance the current efforts to establish potential epidemiological links of MDR transmission between WWTP- and human/animal-associated bacteria. Plasmids play an important role in mediating the transfer of ARGs and the IS-associated ARGs that are carried by conjugative plasmids should be prioritized to tackle the spread of resistance.

https://link.springer.com/article/10.1186/s40168-021-01192-w