摘要

虽然普遍的抗生素耐药性主要归因于过度使用和滥用抗生素引起的选择性压力，但最近越来越多的证据表明，抗生素以外的化学物质，如某些金属，也可以通过共同耐药和交叉耐药机制选择和刺激抗生素耐药性。例如，tetL、mile和oprD基因对抗生素和金属都有抗性。然而，在环境相关的低浓度下(远低于最低抑制浓度[MICs]，也称为亚抑制性)，重金属诱导的潜在的从头耐药性几乎没有被探索。研究发现，重金属Cu ( II )、Ag ( I )、Cr ( VI )和Zn ( II )在环境相关和亚抑制浓度下促进了大肠杆菌菌株之间抗生素抗性基因( ARGs )的偶联转移。进一步探讨了这一现象的机制，包括细胞内活性氧( ROS )的形成、SOS反应、细胞膜通透性的增加和共轭相关基因表达的改变。这些结果表明，广泛存在于各种环境中的重金属的亚抑制水平通过促进ARGs的水平转移而促进抗性现象。本研究从多个方面揭示了低浓度重金属对抗生素耐药性传播的生态效应，强调了加强环境中金属污染物控制的有效政策和技术的紧迫性。

Although widespread antibiotic resistance has been mostly attributed to the selective pressure generated by overuse and misuse of antibiotics, recent growing evidence suggests that chemicals other than antibiotics, such as certain metals, can also select and stimulate antibiotic resistance via both co-resistance and cross-resistance mechanisms. For instance, tetL, merE, and oprD genes are resistant to both antibiotics and metals. However, the potential de novo resistance induced by heavy metals at environmentally-relevant low concentrations (much below theminimum inhibitory concentrations [MICs], also referred as sub-inhibitory) has hardly been explored. This study investigated and revealed that heavy metals, namely Cu(II), Ag(I), Cr(VI), and Zn(II), at environmentally-relevant and sub-inhibitory concentrations, promoted conjugative transfer of antibiotic resistance genes (ARGs) between E. coli strains. The mechanisms of this phenomenon were further explored, which involved intracellular reactive oxygen species (ROS) formation, SOS response, increased cell membrane permeability, and altered expression of conjugation-relevant genes. These findings suggest that sub-inhibitory levels of heavy metals that widely present in various environments contribute to the resistance phenomena via facilitating horizontal transfer of ARGs. This study provides evidence from multiple aspects implicating the ecological effect of low levels of heavy metals on antibiotic resistance dissemination and highlights the urgency of strengthening efficacious policy and technology to control metal pollutants in the environments.

https://www.sciencedirect.com/science/article/pii/S0269749117343592