Institute of Evolution and Marine Biodiversity, KLMME, Ocean University of Chinagrid.4422.0, Qingdao, China.
Laboratory for Marine Biology and Biotechnology, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao, China.
Antimicrob Agents Chemother. 2022 Oct 18;66(10):e0062822. doi: 10.1128/aac.00628-22. Epub 2022 Sep 12.
Because of their extremely broad spectrum and strong biocidal power, nanoparticles of metals, especially silver (AgNPs), have been widely applied as effective antimicrobial agents against bacteria, fungi, and so on. However, the mutagenic effects of AgNPs and resistance mechanisms of target cells remain controversial. In this study, we discover that AgNPs do not speed up resistance mutation generation by accelerating genome-wide mutation rate of the target bacterium Escherichia coli. AgNPs-treated bacteria also show decreased expression in quorum sensing (QS), one of the major mechanisms leading to population-level drug resistance in microbes. Nonetheless, these nanomaterials are not immune to resistance development by bacteria. Gene expression analysis, experimental evolution in response to sublethal or bactericidal AgNPs treatments, and gene editing reveal that bacteria acquire resistance mainly through two-component regulatory systems, especially those involved in metal detoxification, osmoregulation, and energy metabolism. Although these findings imply low mutagenic risks of nanomaterial-based antimicrobial agents, they also highlight the capacity for bacteria to evolve resistance.
由于其极其广泛的谱和强大的杀菌能力，金属纳米粒子，特别是银（AgNPs），已被广泛应用于对抗细菌、真菌等的有效抗菌剂。然而，AgNPs 的诱变效应和靶细胞的耐药机制仍存在争议。在这项研究中，我们发现 AgNPs 并没有通过加速靶菌大肠杆菌的全基因组突变率来加速耐药突变的产生。AgNPs 处理的细菌在群体感应（QS）方面的表达也降低了，QS 是导致微生物群体水平耐药的主要机制之一。尽管如此，这些纳米材料并不能防止细菌产生耐药性。基因表达分析、对亚致死或杀菌 AgNPs 处理的实验进化以及基因编辑表明，细菌主要通过双组分调节系统获得耐药性，特别是那些涉及金属解毒、渗透压调节和能量代谢的系统。尽管这些发现表明基于纳米材料的抗菌剂的诱变风险较低，但它们也突出了细菌进化出耐药性的能力。
