Effects and relevant mechanisms of non-antibiotic factors on the horizontal transfer of antibiotic resistance genes in water environments: A review

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.