摘要
      医院废水中含有丰富的抗生素、抗生素抗性基因和病原体。最后的抗生素耐药性基因（LARGs）包括新德里金属-β-内酰胺 酶基因blaNDM、移动粘菌素耐药性基因mcr和替加环素耐药性基因tet（X），后者对碳青霉烯类、粘菌素和替加环素产生耐药性。LARGs在医院废水处理系统（HWTS）中的存在及其意义尚未得到系统的探讨。在这里，LARG变体被证明在HWTS的影响物和流出物中都很普遍。从废水中收集了989株对最后使用的抗生素产生耐药性的肠杆菌科分离株，并分析了LARG的多种遗传背景。携带质粒的LARGs被证实显示出高的多药表型和可转移性。我们还发现，携带blaNDM-1和mcr-1的质粒在单个大肠杆菌中以及含有两种独特的携带mcr-1质粒的大肠杆菌HM016中共存。这一结果可能会在环境选择压力下加速LARG的共同传播。这些菌株中不同的核心基因排列表明了HWTS的几种进化途径。通过质谱法在体外和体内证实了LARGs的抗性功能。这项研究为HWTS中关键ARGs的多样性、遗传背景和功能提供了新的见解。研究结果引发了人们的担忧，即LARGs可能会进一步扩散到环境中，因此迫切需要对医院废水制定更严格的排放标准和法规。
Abstract
Hospital wastewater contains abundant antibiotics, antibiotic resistance genes (ARGs), and pathogens. Last-resort antibiotic resistance genes (LARGs) include the New Delhi metallo-β-lactamase gene blaNDM, mobile colistin resistance gene mcr and tigecycline resistance gene tet(X) which confers resistance to carbapenems, colistin and tigecycline. The presence and significance of LARGs in hospital wastewater treatment systems (HWTS) have not yet been systematically explored. Here, LARG variants were shown to be prevalent both influents and effluents of HWTS. A total of 989 Enterobacteriaceae isolates that confer resistance to last-resort antibiotics were collected from effluents and multiple genetic contexts of LARGs were analyzed. LARGs-carrying plasmids were confirmed to show high multidrug phenotypes and transferability. We also discovered the co-occurrence of plasmids harboring blaNDM-1 and mcr-1 in single Escherichia coli, as well as E. coli HM016 containing two unique mcr-1-carrying plasmids. This result might accelerate co-dissemination of LARGs under environmental selection pressure. Different core genetic arrangements in these strains suggest several evolutionary pathways in HWTS. The resistance functions of LARGs were confirmed in vitro and in vivo by mass spectrometry. This study provides novel insights into the diversity, genetic context and function of critical ARGs in HWTS. The results raise the concern that LARGs may further spread into the environment, thus, more stringent discharge standards and regulations for hospital wastewater are urgently needed.

https://www.sciencedirect.com/science/article/abs/pii/S0043135421011015