Nano-metal oxides induce antimicrobial resistance via radical-mediated mutagenesis
Nano-metal oxides induce antimicrobial resistance via radical-mediated mutagenesis
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纳米金属氧化物通过自由基介导的诱变诱导抗菌药物耐药性
DOI：
10.1016/j.envint.2018.10.030
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发表时间：
2018
影响因子：
11.8
通讯作者：
Chen Jianmin
中科院分区：
文献类型：
--
作者：
Zhang Ye;Gu April Z;Xie Shanshan;Li Xiangyang;Cen Tianyu;Li Dan;Chen Jianmin
纳米粒子的广泛应用对全球公众健康和环境安全产生了不利影响，引起了越来越多的关注和兴趣。纳米金属氧化物（NMOs）的存在是否可以通过从头突变促进新的抗菌素耐药基因（ARGs）的形成在很大程度上是未知的。在这里，我们证明了两种广泛使用的NMOs可以显着提高CIP和CHL-resistantE的突变频率。而相应的金属离子的作用较弱。0.16-100 mg/L纳米Al 2 O3和0.16-500 mg/L纳米ZnO处理后，抗性突变率分别为对照的1.0-14.2倍和1.1-456.3倍。经5d传代培养，抗性突变株对多种抗生素均表现出抗性，且遗传稳定。我们还探讨了NMOs诱导抗生素耐药性的机制。全基因组测序分析表明，突变基因与单药和多药耐药性以及未检测到的抗生素耐药性相关。此外，NMOs显着促进细胞内活性氧（ROS），这将导致氧化DNA损伤和易于出错的SOS反应，因此，突变率提高。我们的研究结果表明，NMOs可以加速多重抗生素耐药性的诱变，并扩大了对纳米颗粒诱导耐药性机制的理解，这可能对指导纳米颗粒的生产和应用具有重要意义。
The widespread use of nanoparticles has triggered increasing concern and interest due to the adverse effects on global public health and environmental safety. Whether the presence of nano-metal oxides (NMOs) could facilitate the formation of new antimicrobial resistance genes (ARGs) via de novo mutation is largely unknown. Here, we proved that two widely used NMOs could significantly improve the mutation frequencies of CIP- and CHL-resistantE. coliisolates; however, the corresponding metal ions have weaker effects. Distinct concentration-dependent increases of 1.0–14.2 and 1.1–456.3 folds were observed in the resistance mutations after treatment with 0.16–100 mg/L nano-Al2O3and 0.16–500 mg/L nano-ZnO, respectively, compared with those in the control. The resistant mutants showed resistance to multiple antibiotics and hereditary stability after sub-culturing for 5 days. We also explored the mechanism underlying the induction of antimicrobial resistance by NMOs. Whole-genome sequencing analysis showed that the mutated genes correlated with mono- and multidrug resistance, as well as undetected resistance to antibiotics. Furthermore, NMOs significantly promoted intracellular reactive oxygen species (ROS), which would lead to oxidative DNA damage and an error-prone SOS response, and consequently, mutation rates were enhanced. Our findings indicate that NMOs could accelerate the mutagenesis of multiple-antibiotic resistance and expanded the understanding of the mechanisms in nanoparticle-induced resistance, which may be significant for guiding the production and application of nanoparticles.