Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China.
School of Civil and Environmental Engineering, Cornell University, Ithaca, NY, 14853, United States.
Environ Pollut. 2018 Jun;237:74-82. doi: 10.1016/j.envpol.2018.01.032. Epub 2018 Feb 21.
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.
虽然抗生素的广泛耐药性主要归因于过度使用和滥用抗生素所产生的选择性压力，但最近越来越多的证据表明，除了抗生素以外的化学物质，如某些金属，也可以通过共同耐药性和交叉耐药性机制选择和刺激抗生素耐药性。例如，tetL、merE 和 oprD 基因既对抗生素又对金属具有耐药性。然而，重金属在环境相关的低浓度（远低于最低抑菌浓度 [MIC]，也称为亚抑菌浓度）下诱导的新的耐药性几乎尚未被探索。本研究调查并揭示了重金属（Cu(II)、Ag(I)、Cr(VI)和 Zn(II)）在环境相关和亚抑菌浓度下促进了大肠杆菌菌株之间抗生素耐药基因（ARGs）的共轭转移。进一步探讨了这一现象的机制，涉及细胞内活性氧（ROS）的形成、SOS 反应、细胞膜通透性增加以及与共轭相关的基因表达的改变。这些发现表明，广泛存在于各种环境中的重金属亚抑制水平通过促进 ARGs 的水平转移，导致了耐药现象的发生。本研究从多个方面提供了证据，表明低水平重金属对抗生素耐药性传播具有生态影响，并强调了加强控制环境中金属污染物的有效政策和技术的紧迫性。
