摘要
      抗生素耐药性给用抗生素治疗传染病造成了障碍。抗生素耐药性基因（ARGs）的水平转移会加剧抗生素耐药性在水环境中的传播。除了抗生素选择性压力外，多种非抗生素因素也会影响ARGs的水平转移。在此，我们试图全面综述非抗生素因素对水环境中ARGs水平转移的影响和相关机制，特别是人类活动和水处理过程中的污染物。已经确定了四种实现水平基因转移（HGT）的途径，即接合、转化、转导和血管化。非抗生素因素引起的结合频率的变化主要与它们的浓度有关，这符合兴奋性。相关机制包括细胞膜通透性、活性氧、SOS反应、菌毛和相关基因mRNA表达的改变。细胞外DNA诱导的转化可能比其他途径更容易受到非抗生素因素的影响。除噬菌体感染外，非抗生素因子对转导的影响与偶联的影响有许多相似之处。考虑到非抗生素因素刺激的膜囊泡的分泌，可以推断出它们对输精管结扎的影响。此外，在亚抑制或环境相关浓度下，人类活动产生的污染物通常会促进HGT，导致抗生素耐药性的进一步传播。除非达到足够的强度，否则单个水处理过程（如氯化、紫外线处理和光催化）很难抑制ARGs的水平转移。因此，建议采用包含两种或两种以上水处理工艺的协同应用。总的来说，我们相信这篇综述可以阐明人类活动污染物风险评估的重要性，并为开发环境友好和成本效益高的水处理工艺以抑制ARGs的水平转移提供见解。
Abstract
Antibiotic resistance has created obstacles in the treatment of infectious diseases with antibiotics. The horizontal transfer of antibiotic resistance genes (ARGs) can exacerbate the dissemination of antibiotic resistance in water environments. In addition to antibiotic selective pressure, multiple non-antibiotic factors can affect the horizontal transfer of ARGs. Herein, we seek to comprehensively review the effects and relevant mechanisms of non-antibiotic factors on the horizontal transfer of ARGs in water environments, especially contaminants from human activities and water treatment processes. Four pathways have been identified to accomplish horizontal gene transfer (HGT), i.e., conjugation, transformation, transduction, and vesiduction. Changes in conjugative frequencies by non-antibiotic factors are mainly related to their concentrations, which conform to hormesis. Relevant mechanisms involve the alteration in cell membrane permeability, reactive oxygen species, SOS response, pilus, and mRNA expression of relevant genes. Transformation induced by extracellular DNA may be more vulnerable to non-antibiotic factors than other pathways. Except bacteriophage infection, the effects of non-antibiotic factors on transduction exhibit many similarities with that of conjugation. Given the secretion of membrane vesicles stimulated by non-antibiotic factors, their effects on vesiduction can be inferred. Furthermore, contaminants from human activities at sub-inhibitory or environmentally relevant concentrations usually promote HGT, resulting in further dissemination of antibiotic resistance. The horizontal transfer of ARGs is difficult to be inhibited by individual water treatment processes (e.g., chlorination, UV treatment, and photocatalysis) unless they attain sufficient intensity. Accordingly, the synergistic application containing two or more water treatment processes is recommended. Overall, we believe this review can elucidate the significance for risk assessments of contaminants from human activities and provide insights into the development of environment-friendly and cost-efficient water treatment processes to inhibit the horizontal transfer of ARGs.

https://www.sciencedirect.com/science/article/abs/pii/S004896972105645X