摘要

       抗生素耐药性的出现是全世界日益严重的问题。许多研究表明，重金属有助于细菌耐药性在环境中的传播。然而 ,金属在相对低亚致命水平（远远低于最低抑制浓度[MIC]）对抗生素耐药性的作用和机制仍然不清楚。在这项研究中，我们调查了重金属亚致命水平的影响 [Ag （I），Zn （II） 和 Cu （II） 关于抗生素耐药性，并探索了基本机制。结果表明，金属离子的亚致命水平提高了突变率，丰富了对多种抗生素具有显著耐药性的诺沃突变体。 抗变种在经过5天的亚培养后表现出遗传性抵抗力。全基因组分析显示，多种药物和特定药物耐药性所涉及的基因发生了明显的突变， 以及与对数据的抗生素耐药性无关的基因。对于由不同金属诱发的突变体来说，基因变化的数量和特征是截然不同的。这项研究为重金属亚致命浓度诱导抗生素耐药性提供了证据和机械见解，这可能增强各种环境中抗生素耐药性的出现。 应更多地考虑和规范这种长期有害重金属的潜在健康风险。

       The emergence of antibiotic resistance is a growing problem worldwide. Many studies have shown that heavy metals contribute to the spread of bacterial resistance in the environment. However, the role and mechanism of metals at relatively low sublethal levels (far below the minimum inhibitory concentration [MIC]) on antibiotic resistance remains unclear. In this study, we investigated the impact of sublethal levels of heavy metals [Ag (I), Zn (II) and Cu (II) on antibiotic resistance, and explored the basic mechanisms. The results showed that the sublethal level of metal ions increased the mutation rate and enriched Novo mutants with significant resistance to multiple antibiotics. The resistant variants showed genetic resistance after 5 days of subculture. Whole-genome analysis revealed that there are obvious mutations in genes involved in the resistance of multiple drugs and specific drugs, as well as genes that are not related to the antibiotic resistance of the data. For mutants induced by different metals, the number and characteristics of genetic changes are completely different. This study provides evidence and mechanistic insights for the induction of antibiotic resistance in sublethal concentrations of heavy metals, which may enhance the emergence of antibiotic resistance in various environments. More consideration and regulation should be given to the potential health risks of such long-term harmful heavy metals.

https://www.sciencedirect.com/science/article/abs/pii/S0304389419301360